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"}})]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("What are the problems of current therapies?")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("The current treatment of IUA is hysteroscopic surgery. The doctors use hysteroscopy to directly view the adhesion inside the uterine and break it down with a sharp needle (Touhy needle) or powered instruments (electric surgery or laser) 2. However, surgery is associated with potential damage to the residual endometrium, which lead to the high post-surgical recurrence of the adhesions (3.1% to 23.5%)"),i("sup",[i("a",{attrs:{href:"#Description/#reference"}},[e._v("3")]),e._v("-"),i("a",{attrs:{href:"#Description/#reference"}},[e._v("4")])]),e._v(". ")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Several methods to prevent IUA reformations after surgery have been proposed, such as intrauterine device (IUD), intrauterine balloon stent, foley catheter and hyaluronic acid barriers"),i("sup",[i("a",{attrs:{href:"#Description/#reference"}},[e._v("5")])]),e._v(". All these mechanical devices are used to separate the uterine walls physically. Besides, several drugs have been used to improve the regeneration of the endometrium, such as hormonal treatment using estrogens, oestrogen and type 5 specific phosphodiesterase inhibitor"),i("sup",[i("a",{attrs:{href:"#Description/#reference"}},[e._v("6")])]),e._v(".")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("However, most of these efforts were less effective and in most of the situation, these results were controversial due to diverse treatment schedule, different population and measurement involved. A good idea to improve the effect is to combine the mechanical devices and drugs together to sperate uterine walls and regenerate endometrium simultaneously.")]),e._v(" "),i("img",{attrs:{src:"

",width:"60%"}}),e._v(" "),i("figure",[e._v("From "),i("a",{attrs:{href:"https://www.youtube.com/watch?v=GRHVmYsk7eo"}},[e._v("YouTube")])])]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("What are the advantages of cell therapy?")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Cell therapy is an alternative choice for endometrium regeneration because endometrial tissue had an intrinsic capacity of regeneration. Recently a case report of a severe IUA treated with autologous stem cells isolated from a women’s own bone marrow has been reported"),i("sup",[i("a",{attrs:{href:"#Description/#reference"}},[e._v("7")])]),e._v(". She was treated hysteroscopically for severe IUA and a T-shaped IUD was place inside the uterine for 6 months. After the failure of hormonal therapy, endometrial stem cells were implanted inside the uterine. Then a clinical pregnancy was obtained. These pioneering discoveries infer that cell therapy with stem cells may be a good choice for endometrium regeneration.")])]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Why do we choose BMSCs?")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Several sources of stem cells have been proposed for tissue regeneration, and bone marrow mesenchymal stem cells is the most promising cell source of regeneration medicine due to their easy acquisition, self-renewal ability, multi-potential differentiation and weak immunogenicity"),i("sup",[i("a",{attrs:{href:"#Description/#reference"}},[e._v("8")])]),e._v(".")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Bone marrow mesenchymal stem cells also has some inherent problems, such as low abundance (0.001-0.01%) in bone marrow population, low overall number, decreased differentiation potential with age and the invasive isolation procedures"),i("sup",[i("a",{attrs:{href:"#Description/#reference"}},[e._v("9")])]),e._v(". These traits make bone marrow mesenchymal stem cells not enough for clinical therapy, therefore, an alternative convenient cell source would be in favor for clinic interest.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Bone marrow stromal cells (BMSCs) are a heterogeneous population of cells that reside in the bone marrow, which contain a small portion of mesenchymal stem cells. BMSCs can be distinguished from hematopoietic cells in bone marrow by plastic adherence, and can also be easily expanded in culture. BMSCs have immune modulatory properties and can induce angiogenesis and tissue repair, which makes them diverse applications in regeneration medicine"),i("sup",[i("a",{attrs:{href:"#Description/#reference"}},[e._v("10")])]),e._v(".")])]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("How to support the cells in the therapy?")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Considering the low percentage of mesenchymal stem cell in bone marrow, we plan to transplant a high density of BMSCs in the damaged rat uterine to achieve better curative effect on endometrium regeneration. Therefore, an injectable material for BMSC encapsulation is urgently required for supporting the cells in the therapy. ")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Pluronic F-127 (PF-127) is a synthetic FDA-approved compound, which has several therapeutic advantages including low-toxicity, biocompatibility, and thermo-reversibility"),i("sup",[i("a",{attrs:{href:"#Description/#reference"}},[e._v("11")]),e._v("-"),i("a",{attrs:{href:"#Description/#reference"}},[e._v("12")])]),e._v(". Moderately concentrated solution of PF-127 in aqueous media (15-30%, w/w) is liquid at room temperature, but could form hydrogel at physiological temperatures. Hence, PF-127 is widely used in drug delivery and in vivo tissue engineering. Growing evidences have suggested that PF-127 might be a suitable scaffold for cell therapy of BMSCs. ")])]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("What are we doing?")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("This year, we came up a novel approach of treating IUA with bone marrow stem cells (BMSCs) as a chassis. We engineered BMSCs by inserting a growth factor overexpressing circuit to promote wound healing in the uterus. To stick our engineered BMSCs (eBMSCs) to the wound in the uterus, we used the FDA-approved Pluronic F-127 (PF-127) gel as supporting matrix to form a “stem cell woundplast”.")])]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("References")]),e._v(" "),i("a",{staticStyle:{"{display":"none"},attrs:{name:"Description/#reference",id:"Description/#reference"}}),e._v(" "),i("p",{staticClass:"card-text"},[e._v("1.\tConforti, A., Alviggi, C., Mollo, A., Placido, G. D., & Magos, A. (2013). The management of IUA: a review of literature. Reproductive Biology and Endocrinology,11,1(2013-12-27), 11(1), 118.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("2.\tCapellaallouc, S., Morsad, F., RongièResbertrand, C., Taylor, S., & Fernandez, H. (1999). Hysteroscopic treatment of severe IUA and subsequent fertility. Human Reproduction, 14(5), 1230-3.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("3.\tPabuçcu, R., Atay, V., Orhon, E., Urman, B., & Ergün, A. (1997). Hysteroscopic treatment of intrauterine adhesions is safe and effective in the restoration of normal menstruation and fertility. Fertility & Sterility, 68(6), 1141.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("4.\tChen, F. P., & Soong YKHui, Y. L. (1997). Successful treatment of severe uterine synechiae with transcervical resectoscopy combined with laminaria tent. Human Reproduction, 12(5), 943-947.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("5.\tSher, G., & Fisch, J. D. (2000). Vaginal sildenafil (viagra): a preliminary report of a novel method to improve uterine artery blood flow and endometrial development in patients undergoing ivf. Human Reproduction, 15(4), 806-809.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("6.\tNagori, C. B., Panchal, S. Y., & Patel, H. (2011). Endometrial regeneration using autologous adult stem cells followed by conception by in vitro fertilization in a patient of severe IUA. Journal of Human Reproductive Sciences, 4(1), 43-8.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("7.\tNelson, T. J., Behfar, A., Yamada, S., Martinez-Fernandez, A., & Terzic, A. (2009). Stem cell platforms for regenerative medicine. Clinical & Translational Science, 2(3), 222.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("8.\tAbumaree, M. H., Jumah, M. A. A., Kalionis, B., Jawdat, D., Khaldi, A. A., & Altalabani, A. A., et al. (2013). Phenotypic and functional characterization of mesenchymal stem cells from chorionic villi of human term placenta. Stem Cell Rev, 9(1), 16-31.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("9.\tStroncek, D. F., Sabatino, M., Ren, J., England, L., Kuznetsov, S. A., & Klein, H. G., et al. (2014). Establishing a bone marrow stromal cell transplant program at the national institutes of health clinical center. Tissue Engineering Part B Reviews, 20(3), 200-5.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("10.\tKhattak, S. F., Bhatia, S. R., & Roberts, S. C. (2005). Pluronic f127 as a cell encapsulation material: utilization of membrane-stabilizing agents. Tissue Engineering, 11(6), 974-983.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("11.\tMatthew, J. E., Nazario, Y. L., Roberts, S. C., & Bhatia, S. R. (2002). Effect of mammalian cell culture medium on the gelation properties of pluronic f127. Biomaterials, 23(23), 4615-4619.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("12.\tRuszymah, B. H., Chua, K., Latif, M. A., Hussein, F. N., & Saim, A. B. (2005). Formation of in vivo tissue engineered human hyaline cartilage in the shape of a trachea with internal support. International Journal of Pediatric Otorhinolaryngology, 69(11), 1489-1495.")])])])}]}},function(e,t,i){i(34);var n=i(14)(i(36),i(37),"data-v-18f10f7d",null);e.exports=n.exports},function(e,t,i){var n=i(35);"string"==typeof n&&(n=e.id,n,""),n.locals&&(e.exports=n.locals);i(12)("543365e3",n,!0)},function(e,t,i){t=e.exports=i(11)(),t.push([e.id,"#design img[data-v-18f10f7d]{margin-top:20px;margin-left:auto;margin-right:auto;display:block}",""])},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}Object.defineProperty(t,"__esModule",{value:!0});var a=i(16),r=n(a);t.default={components:{MyFooter:r.default}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"igem-page Project",attrs:{id:"design"}},[e._m(0),e._v(" "),e._m(1),e._v(" "),i("my-footer")],1)},staticRenderFns:[function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-header",attrs:{id:"design-header"}},[i("p",{staticClass:"page-title"},[e._v("Design")]),e._v(" "),i("p",{staticClass:"page-subheader"},[e._v("A detailed explanation of the design of the whole project")])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-content",attrs:{id:"design-content"}},[i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("What are we doing?")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("This year, we came up a novel treatment for Intrauterine adhesion (IUA) with bone marrow stem cells (BMSCs) as a chassis. We engineered BMSCs by inserting a growth factor overexpressing circuit to promote wound healing in the uterus. To target our engineered BMSCs (eBMSCs) to the wounds in the uterus, we used the FDA-approved Pluronic F-127 (PF-127) gel as supporting matrix (imagine cells on a woundplast). Additionally, we also added Vitamin C (Vc) to enhance wound healing. What’s more, PF-127 can be poisonous to eBMSCs and Vc can also support eBMSCs. The optimal concentration of PF-127 and Vc was determined with orthogonal experiment and the aid of mathematical models.")])]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Engineering BMSCs")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("To begin with, we chose rat BMSCs as the chassis. Because growth factors have been shown to improve wound healing, so we engineered BMSCs to overexpress various growth factors for IUA treatment. The growth factors were expressed constitutively with a strong cmv promoter, fused with eGFP and 3xFLAG.")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("The circuits")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Chronic wounds may suffer from hypoxia and impaired vascularity, which is absolutely not good for healing"),i("sup",[i("a",{attrs:{href:"#Demonstrate/#reference"}},[e._v("1")])]),e._v(". Angiogenic growth factors can stimulate dysfunctional components in chronic healing"),i("sup",[i("a",{attrs:{href:"#Demonstrate/#reference"}},[e._v("1")])]),e._v(", so we chose them as our primary therapeutic components in our Stem Cell Woundplast. We engineered the growth factor genes downstream of three constitutive promoters, making it constitutively expressed in most eukaryotic cells. Additionally, we fused the gene with an eGFP and 3xFLAG to track and test the protein expression with microscopy or Western blot.")]),e._v(" "),i("img",{attrs:{src:"

",width:"60%"}}),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("VEGF"),i("sub",[e._v("121")])]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Vascular endothelial growth factor (VEGF) is secreted by many types of cells that naturally participated in wound healing"),i("sup",[i("a",{attrs:{href:"#Demonstrate/#reference"}},[e._v("1")])]),e._v(", so we believe it would be safe and efficient to overexpress it in our eBMSCs. VEGF is unique compared to other growth factors, for it functions on various components of the wound healing cascade"),i("sup",[i("a",{attrs:{href:"#Demonstrate/#reference"}},[e._v("2")])]),e._v(". There are five isoforms of VEGF, the chain lengths of which are 121, 145, 165, 189, and 206 amino acids, respectfully"),i("sup",[i("a",{attrs:{href:"#Demonstrate/#reference"}},[e._v("3")])]),e._v(". VEGF121 is freely secreted outward of the cell. In this case, the VEGF121 molecules are secreted into the PF-127 supporting matrix and diffuse to uterus epithelial, so it is the best choice for our eBMSCs.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("bFGF")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Another choice is basic fibroblast growth factor (bFGF). bFGF may be an initiator in angiogenesis"),i("sup",[i("a",{attrs:{href:"#Demonstrate/#reference"}},[e._v("4")])]),e._v(" and is activated by sulfate-degrading enzymes. It may also induce VEGF expression. More importantly, bFGF is necessary to keep BMSCs undifferentiated, making our therapy safer and more controllable. Thus, bFGF is an indispensable component of our Woundplast.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("PDGFA")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Prior studies show that adding Platelet-derived growth factor (PDGF) directly to experimentally designed wounds enhances wound healing"),i("sup",[i("a",{attrs:{href:"#Demonstrate/#reference"}},[e._v("5")])]),e._v(". So, we also included it in our Woundplast together with VEGF121 and bFGF.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Promoter")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("We designed a combination of three promoters and three growth factors and were planning to characterize their expression one by one. The three promoters are CMV promoter (BBa_K404102), EF1a promoter and Ubc promoter. All of them are constitutively-expressed. CMV promoter can be used in most mammalian cells and allows adaptability in transient or stable expression, cytoplasmic expression or secretion. EF1a can be used in most cell types, and the expression level of is stable. Ubc, as the name suggests, is quite ubiquitous in mammals.")]),e._v(" "),i("img",{attrs:{src:"

",width:"60%"}}),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("eGFP and 3xFLAG Dual Reporter")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("It would be of vital importance to visualize and track the expression of the parts, so we fused the growth factor genes with a eGFP gene and a 3xFLAG and constructed a dual reporter. The eGFP allows us to track the expression of the growth factors during the whole experiments including transfection, lentivirus production and infection. The 3xFLAG makes it easier to purify and detect the expression of the growth factors.")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Vitamin C to promote wound healing and eBMSC vitality")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Vitamin C (Vc), also called ascorbid acid (AA), is a crucial antioxidant"),i("sup",[e._v("6")]),e._v(". More importantly, it is involved in all phases of wound healing"),i("sup",[e._v("7")]),e._v(". Thus, we added it to the PF-127 gel to enhance wound healing in combination with other growth factors. Besides, PF-127 can be poisonous to cells. Thus, eBMSCs located in the uterus with PF-127 matrix are prone to apoptosis and cell death. Vc is also able to promote cells from apoptosis and death. However, Vc is acidic, and a low pH is not good for cell growth. Thus, we conducted an experiment with PF-127 concentration gradients to find the optimal condition. ")])]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"

},[e._v("References")]),e._v(" "),i("a",{staticStyle:{"{display":"none"},attrs:{name:"Demonstrate/#reference",id:"Demonstrate/#reference"}}),e._v(" "),i("p",{staticClass:"card-text"},[e._v("1.\tBao, P. et al. The role of vascular endothelial growth factor in wound healing. J Surg Res 153, 347-358, doi:10.1016/j.jss.2008.04.023 (2009).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("2.\tStojadinovic, O., Kodra, A., Golinko, M., Tomic-Canic, M. & Brem, H. A novel, non-angiogenic, mechanism of VEGF: Stimulation of keratinocyte and fibroblast migration. Wound Repair Regen 15, A30-A30 (2007).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("3.\tTischer, E. et al. The human gene for vascular endothelial growth factor. Multiple protein forms are encoded through alternative exon splicing. J Biol Chem 266, 11947-11954 (1991).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("4.\tNissen, N. N. et al. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am J Pathol 152, 1445-1452 (1998).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("5.\tRoss, R., Bowen-Pope, D. F. & Raines, E. W. Platelet-derived growth factor and its role in health and disease. Philos Trans R Soc Lond B Biol Sci 327, 155-169 (1990).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("6.\tMohammed, B. M. et al. Vitamin C promotes wound healing through novel pleiotropic mechanisms. Int Wound J 13, 572-584, doi:10.1111/iwj.12484 (2016).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("7.\tMoores, J. Vitamin C: a wound healing perspective. Br J Community Nurs Suppl, S6, S8-11 (2013).")])])])}]}},function(e,t,i){i(39);var n=i(14)(i(41),i(42),"data-v-1ea89e47",null);e.exports=n.exports},function(e,t,i){var n=i(40);"string"==typeof n&&(n=e.id,n,""),n.locals&&(e.exports=n.locals);i(12)("4ba9c3c2",n,!0)},function(e,t,i){t=e.exports=i(11)(),t.push([e.id,"#results img[data-v-1ea89e47]{margin-top:20px;margin-left:auto;margin-right:auto;display:block}",""])},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}Object.defineProperty(t,"__esModule",{value:!0});var a=i(16),r=n(a);t.default={components:{MyFooter:r.default}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"igem-page Project",attrs:{id:"results"}},[e._m(0),e._v(" "),e._m(1),e._v(" "),i("my-footer")],1)},staticRenderFns:[function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-header",attrs:{id:"results-header"}},[i("p",{staticClass:"page-title"},[e._v("Results")]),e._v(" "),i("p",{staticClass:"page-subheader"},[e._v("The results we achieved and demonstration of our design both "),i("em",[e._v("in vivo")]),e._v(" and "),i("em",[e._v("in vitro")])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-content",attrs:{id:"results-content"}},[i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Results")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Gel Formation Analysis of PF-127")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Before all the experiments on cells, we want to find the lowest concentration needed for PF-127 to form gel at 37℃ but not at room temperature. PF-127 has cytotoxicity (although low), so a lowest concentration is a better choice for application. Besides, if PF-127 at a concentration can only form at 37℃ but not at room temperature, it would be more convenient for us to apply it for clinical use.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Experimental Design")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("We dissolved PF-127 in DMEM/F12 at 4℃ overnight to prepare 40% (w/v) solution, then filter the solution through a 0.45 μM filter and finally kept at 4℃ for use. Then we dissolved 40% (w/v) PF-127 into 5% (w/v), 10% (w/v), 15% (w/v), 20% (w/v), 25% (w/v), 30% (w/v), 35% (w/v), 40% (w/v). Separate each 100μl into 1.5ml EP tube. These tubes were kept at room temperature and at 37℃ for 2min, 5min, 10min. Then we test whether PF-127 form gel by put the tube upside down.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Results")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("According to the formation analysis result, PF-127 cannot form gel at 4℃. At 25℃, 30% (w/v), 35% (w/v) and 40% (w/v) PF-127 can form gel in 5min and 25% (w/v) PF-127 can form gel in 10min. At 37℃, 40% (w/v) PF-127 can form gel in 2min. 25% (w/v), 30% (w/v), 35% (w/v) and 40% (w/v) PF-127 can form gel in 5min at 37℃. Importantly, 20% (w/v) PF-127 can form gel at 37℃ in 10min, but not form gel at room temperature (Figure 1). Therefore, we came up with a conclusion that 20% (w/v) is the concentration we wanted to find.")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 1. Gel formation analysis of PF-127.")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Preparation of BMSCs")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("To begin with, we isolated BMSCs from rats with flow cytometry. There are two main types of cells in bone marrow: stromal cells and hematopoietic cells, so we need to isolate stromal cells for future use.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Experimental Design")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("We isolated BMSCs according to a modified protocol from previous work . Briefly, eight-week old female Sprague-Dawley rats were sacrificed by intraperitoneal injecting 50% chloral hydrate solution, and were then sterilized in 75% ethanol. The femurs and tibiae were collected and bone marrow stromal cells were flushed out using DMEM/F12 medium. The suspended cells were centrifuged at 200 g for 5 minutes, and then seeded in DMEM/F12 media with 10% fetal bovine serum (FBS) and 1% Penicillin/Streptomycin and were incubated at 37℃ with 5% CO2. 2 days later, the non-adherent cells were removed and the culture medium was changed every 3 days.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Results")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("To confirm we isolated BMSCs successfully, we analyzed the cells with flow cytometry. We used CD34 and CD45 as the markers, both of which are typical of hematopoietic cells. As the figure below shows, the majority of the isolated cells were CD34 and CD45 negative, demonstrating they are indeed stromal cells (Figure 2A). The morphology of BMSCs under light microscope was shown on the right panel (Figure 2B).")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 2. Isolation of BMSCs.")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Engineering BMSCs")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Based on our design, we chose CMV promoter for future experiments. CMV promoter is widely used in almost all types of mammalian cells and allows for high-level constitutive expression. We used quantitative reverse-transcription PCR (qRT-PCR) to demonstrate on the RNA level.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Experimental Design")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("On day 1, HEK293T cells were transfected with psPAX2, pMD2.G and our overexpression vector for lentivirus production. BMSCs were plated on 6-well plates on day 2. From day 3, lentivirus particles were harvested every 2 days. The BMSCs were infected for two times. Then, we used 1 μg/mL of puromycin to screen for stably-transfected BMSCs. ")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("We analyzed growth factor overexpression with qRT-PCR.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Results")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("qRT-PCR analysis demonstrated that we successfully overexpressed bFGF and VEGF121 in BMSCs (Figure 3). ")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 3. qRT-PCR analysis result of BMSCs overexpressing bFGF and VEGF121.")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Establishing rat IUA model")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("To test the efficacy of our Woundplast in vivo, we establish a rat model, for no model was developed by others before. The model was evaluated by Hematoxylin-eosin (H&E) staining, Masson staining, measuring endometrial glands number and by calculating percentage of endometrial fibrotic area in rats’ uterine.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Experimental Design")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("The whole procedure of establishing IUA rat model is shown in Figure 4.")]),e._v(" "),i("img",{attrs:{src:""}}),e._v(" "),i("figure",[e._v("Figure 4. Procedure of establishing rat IUA model.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Rats were anesthetized by intraperitoneal injection of 10% chloral hydrate (300 mg/kg), and a vertical incision was made at low abdomen to expose uterine horns. The uterine wall of approximately 0.2 cm was excised 0.5 cm from the left uterine horn, and then mechanical damage of the upper 1.5-2.0 cm endometrium was generated with the spoon scratching, until the inner membrane gave a rough feeling. Finally, the rectus fascia and skin were sealed with a 4-0 nylon suture.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Results")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("In the sham control rats, the glands were uniformly distributed in the surface of uterine endometrial cavity, and collagen fibers were barely observed by Masson staining. Histologic evaluation of the IUA uterine revealed that there was a significant decrease of number of glands in the IUA uterine cavities compared with the sham counterparts (Figure 5A). By contrast, the fibrotic area in the IUA uterine was significantly increased by Masson staining (Figure 5B).")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 5. Analysis of gland number and fibrosis area in rat IUA model")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Together, these results showed that mechanical damage leads to severe intrauterine abnormality, suggesting a successful establishment of rat IUA model.")])]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Demonstrate")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Cell migration and proliferation are two main aspects in wound healing. To demonstrate that our Woundplast indeed accelerated wound healing in vitro, we designed wound healing assay and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay to evaluate cell migration and proliferation, respectfully. Furthermore, we used AS rat model to validate previous achievements in "),i("em",[e._v("vivo")]),e._v(".")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Vc enhanced BMSC survival in PF-127 in "),i("em",[e._v("vitro")])]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("To test if adding Vc to BMSCs indeed promoted BMSC survival rate, we analyzed BMSC apoptosis rate and proliferation with flow cytometry and CCK-8 growth test.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Experimental Design")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Annexin V-FITC/PI apoptosis detection assay was carried under manufacturer’s instructions to evaluate cellular apoptosis according to. Briefly, BMSCs were seeded with different encapsulation conditions for 3 days and 7 days, the cells were trypsinized and suspended in binding buffer, labeled with 5 μL Annexin V-FITC and 5 μL PI for 15 minutes in the dark on ice. Then, 300 μL binding buffer was added to each sample and the cells were evaluated by flow cytometer. Positive control was carried out using 100 μM H2O2 treated for 15 min.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("For CCK-8 growth test, the BMSCs were seeded with different encapsulation conditions. Cell growth of the 3rd day and 7th day after seeding were tested by adding 10% CCK to each well and incubated for 2 hours before measuring the absorbance at 450 nm using a microplate reader.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Results")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("In the early stage, there was a short period of survival enhancement (68.3% versus 51.2%) in PF-127 encapsulation on the first day after seeding. However, after 3 days of culture, majority stromal cells encapsulated in PF-127 started undergoing apoptosis (43.6% versus 62.9%). After 7 days of culture, majority of cells encapsulated in PF-127 with no addition of Vc underwent apoptosis (44.8% versus 77.3%) and detached due to PF-127 cytotoxicity. However, Vc significantly improved in vitro cell attachment at 7 days, while adding 50 μM Vc showed better effect than 100 μM.")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 6. Flow cytometry analysis of BMSCs apoptosis rate in PF-127")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("CCK test also showed that cells encapsulated in PF-127 supplemented with 50 μM Vc proliferated faster in a long term of 7 days culture (Figure 2D), indicating that 50 μM Vc improved cell viability.")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 7. CCK-8 growth test of BMSCs with Vc in PF-127")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("eBMSCs promoted wound healing and cell migration")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("In order to demonstrate that the Woundplast indeed promote wound healing, we conducted the wound healing assay, which is a typical way of testing wound healing ability in vitro. Artificial wounds were created and treated with supernatants from cultured eBMSCs. Then, we calculated wound healing percentage and migration velocity.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Experimental Design")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("HEK293T cells were plated on a 6-well plate. 24 h later, artificial wounds were created by scraping the cell monolayer with a 10 μL pipette tip. Debris were washed with PBS buffer. Because the growth factors are supposed to be secreted from the cell, culture supernatants from eBMSCs were then added. Images were acquired with microscopy.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("To begin with, we calculated wound healing percentage after 24 h. The detailed procedures are as follow (Figure 8).")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 8. Procedure of wound healing assay data analysis")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("The first step was to load the image. Then the image was processed by enhancing contrast, finding edges and adjusting threshold. Finally, the healing area was measured and calculated.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("For measurement of cell migration velocity, we rationalized that only movements perpendicular to the wound matter in healing. 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We conducted MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay to further investigate how our Woundplast would affect human uterus epithelial cell proliferation. MTT assay is a common-used colorimetric assay for measuring cell proliferation. NAD(P)H-dependent cellular oxidoreductase enzymes are capable of reducing the tetrazolium dye MTT to formazan, an insoluble purple substance. Formazan is soluble in DMSO, so the quantity can then be measured by absorbance.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Experimental Design")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Human uterine epithelial cells were plated on a 96-well plate with five replicates in each group. 1 day later, supernatants from corresponding eBMSC group were added. The cells were then incubated for another two days. MTT assay was conducted following instructions from manufactures. 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Those expressions of parameters may lack readability, structure and reusability.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Those defects, however, can be eliminated. And I’ll do my best to modify and enhance the arithmetic to create a new general model for this type of projects.")])])}]}},function(e,t,i){i(50);var n=i(14)(i(52),i(53),"data-v-6dd2a7c5",null);e.exports=n.exports},function(e,t,i){var n=i(51);"string"==typeof n&&(n=e.id,n,""),n.locals&&(e.exports=n.locals);i(12)("43d0869d",n,!0)},function(e,t,i){t=e.exports=i(11)(),t.push([e.id,"#collaborations img[data-v-6dd2a7c5]{margin-top:20px;margin-left:auto;margin-right:auto;display:block}",""])},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}Object.defineProperty(t,"__esModule",{value:!0});var a=i(16),r=n(a);t.default={components:{MyFooter:r.default}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"igem-page HumanPractice",attrs:{id:"collaborations"}},[e._m(0),e._v(" "),e._m(1),e._v(" "),i("my-footer")],1)},staticRenderFns:[function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-header",attrs:{id:"collaborations-header"}},[i("p",{staticClass:"page-title"},[e._v("Collaborations")]),e._v(" "),i("p",{staticClass:"page-subheader"},[e._v("Collaboration with other iGEM teams")])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-content",attrs:{id:"collaborations-content"}},[i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Helped SCUT-China_A to verify lysis gene expression")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("SCUT-China_A is a friendly and open team. We had a meetup and exchanged our project ideas with each other. Besides, we helped each other to complete or repeat some experiments. We helped SCUT-China_A team to repeat the experiment verifying the lysis gene expression by measured the growth curve of our five kinds of engineering bacteria in different concentration of metal ions (Figure 1). They helped us to finish a western blot experiment to test the expression of BBa_K2298002 in 293T cells.")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 1. Verify lysis gene expression by measured the growth curve of our five kinds of engineering bacteria in different concentration of metal ions for SCUT-China_A")])]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Held Annual Biology Festival together with SYSU-Software")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("SYSU-Software is the software team of our university. We collaborated with them to hold the Annual Biology Festival on our campus and exchanged our idea on synthetic biology frequently. Besides, we gave them some advice on the interlab study. They also gave us some advice on our modeling construction part.")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 2. 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After examination of some published work, these concerns could be answered by some of them.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Firstly, several works related to IUA has been done using mouse model"),i("sup",[i("a",{attrs:{href:"#Ethics/#reference"}},[e._v("1")])]),e._v(". In one work, mice were irradiated to be sterilized with no estrous cycles remained. Researches seeks to use BMSCs to rescue the estrous by injecting cells into the tail vein, and similar methods could be one solution for patients who have IUA"),i("sup",[i("a",{attrs:{href:"#Ethics/#reference"}},[e._v("2")])]),e._v(". So, there are still some ethical problems, but they are not so severe to preclude the treatment.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("According to the same report, though lots of works claimed BMSCs would transdifferentiate into endometrial cells, no endothelium was formed from BMSCs. However, only immune cells expressing CD45 marker were detected like CD3"),i("sup",[e._v("+")]),e._v(" T cells and F4/80+ macrophage cells"),i("sup",[i("a",{attrs:{href:"#Ethics/#reference"}},[e._v("2")])]),e._v(". These cells will infiltrate into the endothelium and are good candidates for expressing the growth factor. Because immune cells will not survive for a long time, the unexpected immune responses could be weak. Anyway, real treatment will always use human derived BMSCs first, but using mice derived BMSCs will not cause severe problems.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Additionally, there are concerns that more patient samples need to be accumulated before BMSCs can be applied to real treatment. However, in our cases things are quite different. The method used to change the situation of IUA or fibrosis is through physical surgery. BMSCs were reported to be used only as the recovery method for the injury caused by the operation, and they would prevent the palindromia of IUA"),i("sup",[i("a",{attrs:{href:"#Ethics/#reference"}},[e._v("1")])]),e._v(". The main mission for cases studies for using BMSCs is not about its effects on repairing the injury (which is proved in mice model) but for its potential effects on the normal function of uterine. Still, if there are no side effects of BMSCs in any existed reports, cases of patients will not be of key importance.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("The advantages of using BMSCs are that every time of its application will not necessarily cause damage as we discussed above. The concerns are about its differentiation. We must say that the application of BMSCs is still under preclinical animal model of trials"),i("sup",[i("a",{attrs:{href:"#Ethics/#reference"}},[e._v("3")])]),e._v(". We hope that transplantation of these progenitor cells will stimulate the endometrial lining and that is why growth factors were considered in our case. Strict clinical trials are indispensable. Moreover, the privacy of patients should also be considered as important. Even when the technology and clinical study are comprehensive the transplantation of self or other people’s cells is serious, procedures and security insurance will be necessary before any legal operation could be done.")])]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("References")]),i("a",{staticStyle:{"{display":"none"},attrs:{name:"Ethics/#reference",id:"Ethics/#reference"}}),e._v(" "),i("p",{staticClass:"card-text"},[e._v("1. Alawadhi F, Du H, Cakmak H, Taylor HS: Bone Marrow-Derived Stem Cell (BMDSC) transplantation improves fertility in a murine model of Asherman's syndrome. PLoS One 2014, 9(5):e96662.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("2. Ong YR, Cousins FL, Yang X, et al.: Bone Marrow Stem Cells Do Not Contribute to Endometrial Cell Lineages in Chimeric Mouse Models. Stem Cells 2017.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("3. Salazar CA, Isaacson K, Morris S: A comprehensive review of Asherman's syndrome: causes, symptoms and treatment options. Curr Opin Obstet Gynecol 2017, 29(4):249-256.")])])])}]}},function(e,t,i){i(60);var n=i(14)(i(62),i(63),"data-v-cec55286",null);e.exports=n.exports},function(e,t,i){var n=i(61);"string"==typeof n&&(n=e.id,n,""),n.locals&&(e.exports=n.locals);i(12)("2b39fc0c",n,!0)},function(e,t,i){t=e.exports=i(11)(),t.push([e.id,"#silver .card-letter[data-v-cec55286]{padding:10px;border:2px solid}#silver ul[data-v-cec55286]{padding-left:50px;padding-top:10px;margin:10px 0}#silver img[data-v-cec55286]{margin-top:20px;margin-left:auto;margin-right:auto;display:block}",""])},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}Object.defineProperty(t,"__esModule",{value:!0});var a=i(16),r=n(a);t.default={components:{MyFooter:r.default}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"igem-page HumanPractice",attrs:{id:"silver"}},[e._m(0),e._v(" "),e._m(1),e._v(" "),i("my-footer")],1)},staticRenderFns:[function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-header",attrs:{id:"silver-header"}},[i("p",{staticClass:"page-title"},[e._v("Silver")]),e._v(" "),i("p",{staticClass:"page-subheader"},[e._v("See why we believe our Human Practice meets Silver Medal Requirements")])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-content",attrs:{id:"silver-content" }},[i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Investigations and Talks with Doctor and Patients")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("In order to conduct our Stem Cell Woundplast project, we have to do")]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Consult professors in the field for profession and advice support;")])]),e._v(" "),i("li",[i("p",[e._v("Investigate the possible market to analyze the feasibility and competitiveness of our possible product;")])]),e._v(" "),i("li",[i("p",[e._v("Further discussion to promise Stem Cell Woundplast therapy;")])]),e._v(" "),i("li",[i("p",[e._v("Conducting Survey on Stem Cell Therapy.")])])]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Step 1: Consultation with Professor")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Our group member contacted the professors in the field of IUA before our project. Professor Yuqing Chen from the First Affiliated Hospital of Sun Yat-sen University was interested in our idea and was willing to offer clinical information and guidance to our project.")]),e._v(" "),i("div",{staticClass:"card-letter"},[i("p",{staticClass:"card-text"},[e._v("Brief Talk Example with Doctor:")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("HP")]),e._v(": Good morning! Doctor Chen, we are the iGEM group from Sun Yat-sen University, and this year we are going to the project of Stem Cell Woundplast which can apply to the intrauterine adhesion, also called IUA. You are the botanic physician of intrauterine adhesion in the First Affiliated Hospital of Sun Yat-sen University and we are wondering could you give some suggestions or comments to the project before our work? Next, please let me introduce the function of our Stem Cell Woundplast. We are going to choose BMSCs to be injected into Intrauterine, a kind of stem cell common used for therapy which exhibits properties of multi-potency, underscoring the relevance of the immune response as well as easy maintenance by plastic adherence. What’s more, we are going to design BMSCs with overexpressed cell factors to accelerate the recovery together with Vitamin C, which is commonly used in tissue repair and regulate stem cell self-renewal ability and differentiation, be encapsulated in FDA approved for clinical use, PF-127, which have also been reported that bone marrow-derived mesenchymal stem cells using PF-127 hydrogel in vitro to Adipose differentiation, enlightening the promising function of the BMScs using PF-127. Doctor Chen could you offer some suggestions or comments to our project?")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Doctor Chen")]),e._v(": I am really interested in your project and willing to offer guidance to your work, since intrauterine adhesion is of high incident rate in China, and there is a positive development tendency of stem cell therapy industry in China, your group’s idea for appliance stem cell with PF-127 to the intrauterine adhesion sounds really attractive and workable. Just like smart CAR-t, smart TCRT, I hope your project Stem Cell Woundplast can finally work in clinical use and you are really doing good step to the gynecology problem in China!")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("HP")]),e._v(": Before our project, we also investigate the recovery method in other hospital is using a uterine balloon. Is it the commonly used method to help recovery and prevent recurrence of intrauterine adhesion?")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Doctor Chen")]),e._v(": Nowadays, there is no standardized recovery therapy for intrauterine adhesion in China, the high recurrence rate of the syndrome also bothers most of the patients. We really hope to have a more efficient therapy for intrauterine adhesion.")])]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Step 2: Hospital Investigation")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 1. Investigations among IUA Patients in the First Affiliated Hospital of Sun Yat-sen University.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Before deep discussion and further study of the possibility of our Stem Cell Woundplast to the IUA, we decided to investigate the feasibility and acceptance of bone marrow stem cells (BMSCs) in clinical using. We went to the First Affiliated Hospital of Sun Yat-sen University for a visit and had interviews with patients and doctor involving in IUA clinical treatment. The result showed that our patient had some knowledge about stem cell, showed positive attitudes to our Stem Cell Woundplast to the recovery treatment of IUA, and preferred the promising effective appliance of stem cell therapy to the current physical barrier.")]),e._v(" "),i("div",{staticClass:"card-letter"},[i("p",{staticClass:"card-text"},[e._v("Investigation example among Patients:")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("HP")]),e._v(": Have you ever heard of Stem Cell Therapy and what’s your attitude towards it?")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Patient Song")]),e._v(": I’ve heard that the umbilical cord blood from the newborns contained a lot of stem cell and it could be stored in the hospital and then been taken out for tissue repair therapy or cell differentiation for clinical use when suffering severe diseases. Am I right?")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("HP")]),e._v(": Yes, you really get the main idea of Stem Cell Therapy. We have a project Stem Cell Woundplast using the Stem Cell Therapy principle to help cure the intrauterine adhesion. In our project, we may use the stem cell which is not from the patient but other safe sources, for example, from labs. We try to apply stem cell through injection to the intrauterine without entering into a human internal environment and be removed from the patient’s body with the menstruation. What we attach great importance to this therapy is that it could be more efficient for recovery and reduce the recurrence rate according to the theory. Do you think this kind of therapy is acceptable? ")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Patient Song")]),e._v(": Is there any example of Stem Cell Therapy in clinical use?")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("HP")]),e._v(": We are now doing the investigation before our project but there are some Stem Cell Therapies in other fields. It is reported that in 2015 in Korea, four macular degeneration patients were treated with embryonic stem cell-derived retinal pigment epithelium cells. After a one-year follow-up, there showed no serious side effects associated with treatment (tumor growth or other unexpected effect). And recently, scientists from Australia have also found stem cell therapy or may help treat dementia.")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Patient Song")]),e._v(": Oh I see. Then my answer is absolutely yes! I accept stem cell therapy, because it plays a promising as well as more and more important role in curing diseases. I am willing to try the more advance therapy with hopefully reduced recurrence rate than the traditional uterine balloon stent as well as other physical barrier.")])]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Step 3: Further discussion with Doctor Chen")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 2. Further Discussion with Doctor Chen in the First Affiliated Hospital SYSU.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("We discussed the performance of our project to IUA with Doctor Yuqing Chen. The BMSCs with overexpressing growth factors and Vitamin C (VC) together be surrounded by the FDA-approved Pluronic F-127 (PF-127) gel. Then through intrauterine injection to locate our Stem Cell Woundplast to the likely adhesion place, after which the stem cell and the growth factors would function to promote wound healing and then be removed from the patient’s body with the menstruation. Doctor Chen said it was a promising therapy for clinical treatment but it still needed further clinical tests and the approval of Three Phases Clinical Trials.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("We also mentioned the ethics of the appliance of Stem Cell Woundplast. Doctor Chen advised us to go through international ethics standards for business and the examples for stem cell therapy in other clinical treatment. With the doctor’s advice, we also conducted investigation among the patients in IUA patient ward. ")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Step 4. Survey about Stem Cell Therapy")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Stem cell therapy is receiving more and more attention. As biological majored students, we have background knowledge and interest in improving and introducing stem cell therapy, but we want to know other people’s opinions: how well do they know about stem cell therapy? What is the main concern of stem cell therapy for them? How can this concern be eliminated? How well can our project help? Thus, we carried out a survey. Since we wanted to discuss this question more detailed, many terminologies were used that might be hard for everyone to understand, so the survey was mainly carried out upon people that received higher-education.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("The following is the analysis of the survey.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Part 1 Educational background of informants.")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 3. Pie Chart of Education Background Information")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 4. Pie Chart of Information about Majors among informants.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("From these two pie charts we could see our informant from investigations were mostly highly educated (About 94% were in university), and a lot of people were majoring in biology, physiology or medicine (64%). There were also people from other majors who were interested in this issue and took part in filling our questionnaire. Generally, we had a reliable feedback to support our result.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Part 2 How well do these people know about stem cell therapy.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Q1: All you familiar with Stem Cell Therapy?")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 5. Pie Chart of Familiarity of Stem Cell Therapy among Informants.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("More than half of the participants were familiar with Stem Cell Therapy (79%). From feedbacks after filling the questionnaire, we knew that many people came into this word many a time, yet had not looked detailed into this issue. Therefore, it is helpful to introduce more about Stem Cell Therapy to the public.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Q2: What kind of problems of stem cell therapy do you concern about most?")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 6. Pie Chart of Concerning Problems with Stem Cell Therapy among Informants.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Q3: What do you think would affect the feasibility of stem cell therapy? (Multiple Selection)")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 7. Histogram of Difficulties of Feasibility of Stem Cell Therapy among Informants.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Tumorigenesis (34%) and stability of stem cells (30%) were two core problems that people concerned about. “Homing or not” (8%) may not a concerning problem to most people. Specified studies (125 in number) and assessment system (94 in number) were both needed to be perfect. On the other hand, ethic issues were not a severe problem (53 in number).")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Part 3 Problems in stem cell therapy.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Q4: What do you think is related to the curative effect of stem cell therapy?")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 8. Histogram of Curative Effect of Stem Cell Therapy among Patients.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Q5: Considering stem cells proliferate with the effect of stem cell therapy, it is?")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 9. Pie Chart of Considering Stem Cells Proliferate with the effect of Stem Cell Therapy.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("As for the comments on the proliferation in Stem Cell Therapy, 54% of the people thought that it was valuable for reference and 42% of them thought it was vital and necessary. This pointed out that the majority of people had the same thought with us, and that our project would be meaningful if put into usage.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("We carried out question eight to further specify the significance of our project to stem cell therapy, and found that our project was thought to have a practical meaning for both safety (30%) and feasibility (35%) issues. ")])])])}]}},function(e,t,i){i(65);var n=i(14)(i(67),i(68),"data-v-777c2890",null);e.exports=n.exports},function(e,t,i){var n=i(66);"string"==typeof n&&(n=e.id,n,""),n.locals&&(e.exports=n.locals);i(12)("5230cead",n,!0)},function(e,t,i){t=e.exports=i(11)(),t.push([e.id,"#gold img[data-v-777c2890]{margin-top:20px;margin-left:auto;margin-right:auto;display:block}",""])},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}Object.defineProperty(t,"__esModule",{value:!0});var a=i(16),r=n(a);t.default={data:function(){return{activeName:"1"}},components:{MyFooter:r.default}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"igem-page HumanPractice",attrs:{id:"gold"}},[e._m(0),e._v(" "),i("div",{staticClass:"page-content",attrs:{id:"gold-content"}},[e._m(1),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Further marketing analysis")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("We have achieved some experiment results so far. As for an iGEM competition, our project is completed, but we want to know whether our project has social and commercial significance. Therefore, we further analyzed whether our project can meet the needs of the society and market based on the current experimental progress. We used the PESTEL analysis method to analyze the external macro environment of our project and used the SWOT analysis method to analyze whether our project has the value of further research and even commercialization.")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("PESTEL analysis")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("PESTEL analysis (political, economic, social, technological, environmental and legal) describes a framework of macro-environmental factors used in the environmental scanning component of strategic management. It is part of an external analysis when conducting a strategic analysis or doing market research, and gives an overview of the different macro-environmental factors to be taken into consideration. It is a strategic tool for understanding market growth or decline, business position, potential and direction for operations. (From Wikipedia)")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Our PESTEL analysis shows that our project has a good macro-environment. Please check the details bellow.")]),e._v(" "),i("el-collapse",{attrs:{accordion:""},model:{value:e.activeName,callback:function(t){e.activeName=t},expression:"activeName"}},[i("el-collapse-item",{attrs:{title:"Political",name:"1"}},[i("p",{staticClass:"card-text"},[e._v("Stem cell technology is an emerging technology that the Chinese government strongly supports. The Chinese government attaches great importance to research in the field of stem cells. In 2016, the Chinese Government established the “13th Five-Year” National Key Research and Development Program, “Stem Cell and Transformational Research” is one of the key special projects. The government expects to allocate 850 million RMB ($127.8 million) to 28 stem cell-related types of research in 2017, including clinical research on stem cells.")])]),e._v(" "),i("el-collapse-item",{attrs:{title:"Economic",name:"2"}},[i("p",{staticClass:"card-text"},[e._v("At present, China's stem cell industry is developing rapidly, and the relevant economic environment is good. China’s stem cell industry grew by 48.9 percent in five years during the 12th Five-Year Plan period, with a growth of more than 60 percent in 2013-2015 and nearly 30 billion RMB in 2015, with a projected growth to 230 billion RMB by 2020, according to a report published by HwaBao Securities Co.Ltd. Therefore, on the economic side, our project has a good environment for development.")])]),e._v(" "),i("el-collapse-item",{attrs:{title:"Social",name:"3"}},[i("p",{staticClass:"card-text"},[e._v("At present, China's society is very much in need of a better IUA treatment program, our project is very in line with the needs of the community. In recent years, the Chinese government has opened up the “Two-child policy”, which has greatly stimulated the nation's desire for birth. And IUA may lead to infertility, which will seriously affect the family happiness of patients and is not conducive to China's population stability. Moreover, the traditional and conservative views to sex are changing, which leads to an increasing rate of induced abortion, which means that the number of Chinese patients with IUA may be very large. We estimate in the feasibility analysis of the project that there are 500,000 patients per year in China.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("In addition, China's social climate is very tolerant for stem cell therapy. Our survey of the general public showed that most of the respondents had a certain understanding of stem cell therapy. In our interviews with patients with IUA, patients are more likely to accept better medical solutions from new technologies. Therefore, we believe that the current social environment in China is very suitable, and China needs further researches in this area.")])]),e._v(" "),i("el-collapse-item",{attrs:{title:"Technological",name:"4"}},[i("p",{staticClass:"card-text"},[e._v("At present, the necessary supporting technology for our project is mature. In terms of upstream technology, China's stem cell upstream industry technology is very mature. The BMSCs we used in our experiments were extracted by ourselves, but we can also buy them for 1500RMB ($226)/strain (2 x 10^6). Other reagents and consumables are available from various biological companies. The downstream technology is simple. When we've completed the stem cell modification and gel preparation, the hospital just needs to stick the Stem Cell Woundplast to the cut surface. So our project will not be constrained by external technical conditions.")])]),e._v(" "),i("el-collapse-item",{attrs:{title:"Environmental",name:"5"}},[i("p",{staticClass:"card-text"},[e._v("Our project is environmentally friendly. Most of our experiments are done in cell culture room isolated from the outside world, and there is a uniform collection point for the waste generated during the experiment. All experimental waste collected will be handled by the relevant companies, so the impact on the environment can be minimized. Our final product is just as environmentally friendly, with stem cells are prone to cell apoptosis or death in uterine environment and the use of PF-127 is legal and safe degradable. You can view the Safety page for details.")])]),e._v(" "),i("el-collapse-item",{attrs:{title:"Legal",name:"6"}},[i("p",{staticClass:"card-text"},[e._v('In 2015, the National Health & Family Planning Commission, and China Food and Drug Administration promulgated the "Stem Cell Clinical Research Management Approach (Trial)". It normalizes and promotes the Chinese stem cell clinical research. But the bill is aimed at the use of human stem cells for clinical research, and there is no indication of clinical studies of mouse stem cells. So in the future, we need more perfect laws and policies to be promulgated before we can legally conduct clinical research.')])])],1),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("SWOT analysis")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("SWOT analysis (strengths, weaknesses, opportunities, and threats), is a structured planning method that evaluates those four elements of an organization, project or business venture. It involves specifying the objectives of the business venture or project and identifying the internal and external factors that are favorable and unfavorable to achieve that objective. (From Wikipedia)")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Strengths")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("1. Cell source is stable and low cost: The stem cells we use are isolated from rats that commonly used in scientific research. It has been commercialized in China and can be purchased directly. Therefore, the cost of obtaining stem cells is much lower than that extracted from infant umbilical cord blood or from patients' peripheral blood and is more stable in quantity.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("2. The cost of treatment is low: When we estimated the cost of the experiment at the present stage, it was found that the cost of the materials for the experiment is only 750RMB ($ 112). We expected that most of the cost will come from the trial phase of the experiment, and after our experimental conditions are fully explored, we expect to conduct an experimental operation with the cost lower than 900 RMB ($ 136). The cost of surgery in Chinese hospitals to put the gel into the uterine cavity is very low, so the cost of treating a patient with our scheme will possibly be less than 1200RMB ($ 180).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("3. High profitability: Currently, stem cell therapy in China is mainly based on peripheral blood stem cells and baby cord blood stem cells. Because of the difficulty of acquiring and conserving these cells, the cost of stem cell therapy is usually above 10,000 RMB ($ 1,500). This makes the patient's psychological expectations of stem cell treatment costs higher. We learned from Professor Yuqing Chen that the current Chinese patients receiving a hysteroscopic surgery and postoperative recovery, need to pay about 15,000 RMB ($ 2,255). So if this therapy can be truly commercialized in the future, it will still be very popular even priced to 3,000 RMB ~5,000 RMB ($ 450 ~ $ 750), which provides a profit margin of 300 % ~ 500 %. ")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("4. Biosafety: Our product uses PF-127 gel to wrap engineering stem cells. As cells do not enter the human milieu interne and even do not directly contact with human tissues, it can effectively prevent the potential immune rejection. And this kind of cells in our experiments has been maintaining normal function. There is no mutation phenomenon. In actual treatment, our engineered cells will naturally die after a short period of working time and will not proliferate abnormally in the uterine cavity. The hydrogel material will be expelled from the uterine cavity with menstruation after the patient's menstrual period is restored.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("5. Patients’ high recognition: in China, the high risk population of IUA is 20~29-year-old young women, judging from our interviews with patients, we found that the well-educated younger generation in China commonly has a basic understanding of stem cells. Stem cell therapy is widely believed to be a very effective new treatment, and patients are willing to spend more money on new technologies than traditional treatments.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Weaknesses")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("1. Traditional therapies cannot be completely replaced: Our Stem Cell Woundplast is suggested to be used in conjunction with the uterine balloon stent, and in moderate or severe cases it may be difficult to serve alone. So patients will pay an extra fee for stem cell therapy.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("2. Scaling difficulties: Currently, our Stem Cell Woundplast can only be produced in laboratories, which cannot be mass-produced because of laboratory size and staffing constraints. At present, China does not have the technical means of automatically doing gene engineering and cell culturing experiment, so it is difficult to expend the scale.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("3. Large pre-investment in commercialization: At present, a large amount of investment is needed to complete further experiments to pass clinical trials. And after clinical examination, in order to commercialize the product, we need large-scale cell experiment platform and a large number of skilled experiment operators. Equipment, reagents and manual inputs will be very expensive.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("4. There are geographical limitations: At present, only 30 hospitals in China have been authorized to provide stem cell treatment services, most of which are located in the developed areas along the southeast coast of China. The vast, underdeveloped interior of China has few hospitals qualified for stem cell therapy, so how to address the needs of patients in China's interior is a huge challenge.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Opportunities")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v('1. Strong market demand: Although there are no official statistics on how many IUA patients there are in China, the number of IUA patients can be inferred from the known statistics and the number of cases in hospitals, which is probably huge. And because of the Chinese government\'s opening of the "second child" policy in recent years, the national desire to have children has increased greatly, and IUA will cause menstrual disorders and infertility, which will further stimulate the demand for treatment of IUA.')]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("2. National Policy Support: In 2016, the Chinese Government established the “13th Five-Year” National Key Research and Development Program, “Stem Cell and Transformational Research” is one of the key special projects. The government expects to allocate 850 million RMB ($127.8 million) to 28 stem cell-related types of research in 2017, including clinical research on stem cells.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("3. Excellent hardware and software: Sun Yat-sen University is the first-class university in China. Its Life Sciences College ranks among the top 10 in the country, the Medical College is among the top five in the country. Its third affiliated hospital and ophthalmology hospital are among the first bench of medical institutions allowed to conduct clinical research on stem cells in China. So we have the capability to support the study.")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Threats")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("There is no precedent in China for using mouse stem cells to treat human diseases, which may cause problems when clinical studies are filed in the future.")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Conclusion")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("The market for stem cell bandages is huge. At present, the stem cell industry in China is developing rapidly, and the stem cell therapy is very promising. Because of the high prevalence of artificial abortion and hysteroscopic surgery in China, a large number of women are under the threat of uterine adhesion. Therefore, the use of stem cells in hysteroscopic uterine adhesion separation (TCRA) postoperative recovery treatment has a wide market capacity and important social significance.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Our project has strong market competitiveness. Our treatment is more costly than traditional post-operative recovery program, but it will have better recovery effects, and because stem cell therapy is generally expensive, our treatment is less expensive than patients' psychological expectations. As a leading biomedical technology, stem cell therapy has high recognition in China, and patients are more inclined to choose new and better treatments and are willing to pay higher fees.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("The commercialization of our project will have considerable profitability. Compared to the use of human stem cells for treatment, our Stem Cell Woundplast program costs very low, so our product pricing space is very large, can more calmly balance the profits, product competitiveness and patients’ needs. As discussed above, our products can reach more than 300 % profit margin, only take our Guangzhou as an example, the First Affiliated Hospital of Sun Yat-sen University carries out more than 700 cases of intrauterine adhesion in one year even disintegrating, if all of our restorative therapies are used, there will be 2.1~3.5 million RMB ($ 316.8~528.0 thousand) of profit; in Guangzhou, there are 36 hospitals at the same level as the First Affiliated Hospital of Sun Yat-sen University, and the number is 773 in the whole China, which means that the project will have a very outstanding profitability in the future.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("And the Chinese government is pushing hard for stem cell research, and a lot of money and expertise are pouring into the field, making it possible to make rapid progress in stem cell research.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("As for the disadvantages and threats, we think that we can reduce the impact to the minimum through reasonable strategies. Most importantly, we should pay more attention to the biological safety aspect, in order to pass the clinical examination. In the initial stage of commercialization, as the productivity is low, we can raise the price of treatment and position the main customer groups in high-income populations. After the accumulation of funds to expand the scale, the price can be reduced. However, unlike in the laboratory, after commercialization, labor costs will be more expensive, and we expect that the price of this treatment will be high for a longer period of time, but affordable for residents in developed areas. At present, some enterprises have made considerable achievements in developing experiment robots, and we believe that when they have the ability to semi-automatically and even automatically produce the engineering stem cells, the cost of this treatment will be reduced to even lower. And China's economy and infrastructure are developing rapidly. In the near future, hospitals in underdeveloped regions may have the stem cell therapy qualification, and the income of the residents will also be greatly improved; by then, Stem Cell Woundplast will truly become a common means of postoperative recovery.")]),e._v(" "),i("p",{ staticClass:"card-text"},[e._v("For these reasons, we believe that the project is well worth further research and even commercialization.")])],1)]),e._v(" "),i("my-footer")],1)},staticRenderFns:[function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-header",attrs:{id:"gold-header"}},[i("p",{staticClass:"page-title"},[e._v("Gold")]),e._v(" "),i("p",{staticClass:"page-subheader"},[e._v("See why we believe our Human Practice meets Gold Medal Requirements")])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Project Feasibility Analysis")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("At the very beginning of our project, the first two questions we are concerned about are whether we have the ability to complete the project and whether our project has commercial or even social significance. In order to solve the latter problem, our HP group made a project feasibility analysis to explore whether the project is worthy of our efforts. ")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Market Volume")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("According to our survey, we believe that the market capacity of this project is very impressive.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Stem cell therapy is a fast developing industry with a very optimistic prospection in both global and domestic market. It is expected that in the next few years, the global and China's stem cell treatment industry will rapidly expand. According to research data from the international research institute Market Research and Transparency Market Research, the global stem cell market witnessed a noticeable increase from $ 21.5 billion in 2010 to $ 98 billion in 2017. It is expected that the potential market size of global stem cell will enjoy the climbing trend to $ 119.5 billion in 2018, nearly six times as many as the original point.")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 1. Market Volume of the Global Stem Cell Industry."),i("br"),e._v("(Data from Market Research and Transparency Market Research)")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("In China, the government is vigorously promoting the development of stem cell industry. In 2006 the State Department listed stem cell research as a key technical field in the national major science and technology strategic development plan for the first time. On July 20, 2015, the National Health & Family Planning Commission, and China Food and Drug Administration promulgated the \"Stem Cell Clinical Research Management Approach (Trial)\". This means that China's comprehensive and orderly development of stem cell clinical research has been started. According to China's investment institutions’ analysis report on the stem cell industry, it is expected that by 2020, the total size of China's stem cell industry should be between 150 to 230 billion yuan(22.5~34.5 billion US dollars). At present, the stem cell collection and storage in China, the relevant biological reagents and equipment supply is sufficient; the government also announced a number of hospitals with stem cell treatment qualification (there is thirty qualified hospital in China). In conclusion, this is the right time to do the stem cell therapy research in China.")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 2. Market Volume of the Chinese Stem Cell Industry. "),i("br"),e._v("(Data from HwaBao Securities Co.Ltd)")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("We know that intrauterine adhesion (IUA) is mainly due to abortion and curettage, and may cause menstrual disorders and infertility and other adverse consequences. We interviewed Professor Yuqing Chen, a gynecologist at the First Affiliated Hospital of Sun Yat-sen University. She pointed out that there are about 13 million people in China each year receiving artificial abortion operation, 63% of which are young women aged 20 to 29 and the vast majority is unmarried. 50% of the patient suffered from the recurrent miscarriage. And each year, the Chinese gynecologists carry out about 1 million hysteroscope operations. This means that many people in China are at high risk of intrauterine adhesions. We can’t get the exact number of the IUA patients, but from the case of some hospital records, we have reason to speculate that the patient population is very large. To the First Affiliated Hospital of Sun Yat-sen University, for example, the case records show that from January 1, 2016, to October 31, 2016, the diagnosis number of IUA was more than 1,000 people, and there were 712 cases of surgery. This is the data from one ordinary grade A class 3 hospital, and there are 773 grade A class 3 hospitals in China, and the number of lower class hospitals is even larger. So we estimate that the number of patients in China is around 500,000 per year. Even worse, IUA may cause infertility, and statistics data shows that the average age of Chinese women's first birth is about 29 years old, from a physiological point of view, 25 to 29 years old are the best time for a women to become a mother, so IUA in China has become a severe social problem that must be solved. Therefore, we believe that the use of stem cells to promote IUA postoperative recovery has a very optimistic market prospects, and it will contribute to the statement of Chinese population.")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("The Current Status of Traditional Postoperative Recovery Therapy")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("At present, the most popular postoperative recovery therapy in Chinese hospitals is using uterine balloon stent and other physical barrier supported with estrogen. Biological glue and amniotic membrane transplantation and other means are under researched, but no relevant case analysis has been reported. According to the case report of the Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, April 2014 to May 2014, patients were treated with uterine balloon stent to prevent wound adhesions. After 48 hours, the patients were treated with the IUD to block the wound, while moderate and severe patients (March classification standard) would receive a 3 months estrogen and progesterone therapy. Even so, the report shows 11 cases of recurrence in 42 cases, the recurrence rate reach to 26.2%. This shows that the current recovery means have two main shortcomings, one is a long recovery period, the other one is the high recurrence rate, which may have a great impact on the lives of patients, and is in an urgent need of improvement.")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Project Description")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Our project is making a Stem Cell Woundplast. We choose bone marrow stem cells (BMSCs) as a chassis, inserting a growth factor overexpressing circuit to promote wound healing in the uterus. We used the FDA-approved Pluronic F-127 (PF-127) gel to locate the BMSCs to the postoperative wound (like a woundplast) and provide a physical barrier. And Vitamin C (VC) is added to the gel to enhance wound healing and support our engineered BMSCs (eBMSCs). In our design, the PF-127 gel will replace the IUD in the traditional postoperative recovery therapy, and the eBMSCs and VC will promote a fast wound recovery. If succeed, the Stem Cell Woundplast can shorten the convalescence, and since the wound will be well covered and quickly recovered, the recurrence rate is likely to decrease. It will probably be used along with the uterine balloon stent in the clinical treatment, which means it won’t completely replace the traditional therapy but serve as a supplement and improvement to it.")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Conclusion")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("There is a huge population of IUA patients in China, they need proper therapy to restore their family life. But the current postoperative recovery therapy is dissatisfactory. Our project has the possibility to overcome this shortcoming, so it’s helpful to solve this social problem and has a very optimistic commercial prospect. Therefore, we think this project is feasible and worth laboring for.")])])}]}},function(e,t,i){i(70);var n=i(14)(i(72),i(73),"data-v-1de43802",null);e.exports=n.exports},function(e,t,i){var n=i(71);"string"==typeof n&&(n=e.id,n,""),n.locals&&(e.exports=n.locals);i(12)("f9ee4b4a",n,!0)},function(e,t,i){t=e.exports=i(11)(),t.push([e.id,"",""])},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}Object.defineProperty(t,"__esModule",{value:!0});var a=i(16),r=n(a);t.default={components:{MyFooter:r.default}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"igem-page HumanPractice",attrs:{id:"safety"}},[e._m(0),e._v(" "),e._m(1),e._v(" "),i("my-footer")],1)},staticRenderFns:[function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-header",attrs:{id:"safety-header"}},[i("p",{staticClass:"page-title"},[e._v("Safety")]),e._v(" "),i("p",{staticClass:"page-subheader"},[e._v("See how we stressed safety issues regarding our project this year")])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-content",attrs:{id:"safety-content"}},[i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-text"},[e._v("Safety has always been a serious issue we considered from the design of the project all the way to lab work. We believe it is of vital importance in iGEM competition, and even more important for us, as we chose Therapeutic Track this year. We set strict rules regarding lab safety, and discussed some potential problems may come into existence in the future clinical application of our project.")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Lab Safety")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Our project this year involves gene overexpression with lentivirus delivery. Many experiments were conducted in a cell culture room; thus, we find it crucial to set clear and strict rules and guidelines to make sure the safety of our team members and to avoid contamination. We talked to our PIs and did an extensive search on the Internet and formulated the SYSU-CHINA Lab Safety Rules.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("In terms of the use of lentivirus, we also made great effort to make sure the whole experiment is safe to the conductors, at the same time minimum its environmental bio-hazards."),i("br"),e._v("We used the psPAX2 vector and pMD2.G vector as the lentiviral packaging and VSV-G envelope expressing plasmid, respectfully (psPAX2 and pMD2.G were gifts from Didier Trono to Addgene). These vectors were modified to prevent the lentivirus from being contagious. To avoid potential contamination to the environment, all the materials and equipment used were processed with Benzyldodecyldimethylammonium Bromide (C21H38BrN).")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Handle Laboratory Animals")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("We talked to our instructors about this issue seriously and made sure that all animal experiments were performed according to protocols approved by the Committee on Animal Care at the School of Life Sciences, Sun Yat-Sen University, China.")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Clinical Safety")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Although our project does not involve any clinical experiments, the ultimate goal of our project includes developing new treatment for IUA. Thus, we considered potential safety issues that may come into existence in the future clinical situation.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("To begin with, we believe the use of PF-127 is legal and safe, for it is approved by US Food and Drug Administration and there it has been used for drug delivery before 1. BMSCs are prone to cell apoptosis or death in uterine environment, making them almost impossible to differentiate into other types of cells. But how they behave exactly needs further study")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("We think the most dangerous aspects of our project is the use of growth factors. VEGF121, bFGF and PDGFA all enhance angiogenesis 2. So, they may promote cancer progression at the same time. We believe a trade-off is necessary. These three growth factors are naturally participated in wound healing. It is a rationale to say that by controlling the dosage of the growth factors, the safety risks can be minimized. In real clinical situations, physicians might need to avoid using this treatment on patients who have had cancers before or who are at high risks. But please keep it in mind that clinical safety is a serious and complicated topic, we are just talking about the most simplified situations here.")])])])}]}},function(e,t,i){i(75);var n=i(14)(i(77),i(78),"data-v-106ae7b8",null);e.exports=n.exports},function(e,t,i){var n=i(76);"string"==typeof n&&(n=e.id,n,""),n.locals&&(e.exports=n.locals);i(12)("0cb55d9c",n,!0)},function(e,t,i){t=e.exports=i(11)(),t.push([e.id,"#public-engagement img[data-v-106ae7b8]{margin-top:20px;margin-left:auto;margin-right:auto;display:block}",""])},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}Object.defineProperty(t,"__esModule",{value:!0});var a=i(16),r=n(a);t.default={components:{MyFooter:r.default}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"igem-page HumanPractice",attrs:{id:"public-engagement"}},[e._m(0),e._v(" "),e._m(1),e._v(" "),i("my-footer")],1)},staticRenderFns:[function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-header",attrs:{id:"public-engagement-header"}},[i("p",{staticClass:"page-title"},[e._v("Public Engagement")]),e._v(" "),i("p",{staticClass:"page-subheader"},[e._v("See how we tried to influence the other people with our knowledge and experience")])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-content",attrs:{id:"public-engagement-content"}},[i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Biology Festival")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Biology Festival is a traditional public educational festival of School of Life Science, SYSU. As our campus is opened to the public, both students and other citizens can join the carnival. This year, the carnival of Biology Festival is held on April 16th, and our team successfully applied to take part in this project. ")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Together with SYSU Software, we invented teams from the South China University of Technology and South China Agricultural University to introduce Synthetic biology to the public. In order to attract people’s attention, we design some funny games about Synthetic biology and prepared snacks for those who won the games. Each team printed their own poster to explain their project, and we shared a big poster that introduced Synthetic biology. Our team members stayed in our tents to organize the games and explain the poster. We took this job, in turn to make sure that visitors would be well served whenever they came. ")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("During the whole day, we received many types of visitor, including students major in Life Science, students major in other aspects, elementary school students and their parents, middle school students and retired medical professor. Different types of visitors have different focuses of attention. Our youngest visitors interested in the games and snacks. For them, we explained several basic biological definitions for them, then provided them pencils and paper and let them draw down their own comprehensions, then they would exchange their paper and gassed what their partner was drawing. Middle school students started to be curious about what is Synthetic biology, so we change the basic biological definitions into high-frequency vocabulary in Synthetic biology to help them understand what is Synthetic biology, how can Synthetic biology change our life. A college student might ask questions about how we were planning to implement our project, and students major in Life Science would show more interest in technical details. Our eldest visitor, the retired professor, seemed very glad to see young people participate in an academic competition like iGEM. He showed strong interest in our project, after consulting some technical detail, he started to share his working experience of the past decades, which was very instructive for us.")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("students are playing games about Synthetic biology")])]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Central China iGEM Consortium (CCiC)")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("From 26th to 28th, August 2017, our team SYSU-CHINA met with another 83 iGEM teams from all over China in Fuzhou City of the Fujian Province to participate in the 4th Central China iGEM Consortium (CCiC). During the event, the participants presented their knowledge and skills and demonstrated the strengths of their teams. During refreshments and the poster sessions, we communicated with other teams and had intense discussions on the essence of synthetic biology. In addition, we organized an academic salon, where participants from various backgrounds got to put their ideas together, giving helpful insights on our projects.")]),e._v(" "),i("img",{attrs:{src:"",width:"80%"}}),e._v(" "),i("figure",[e._v("Yu Tao and Zerun Mao were giving the talk and our booklet.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Additionally, we were honored to give a special talk on how we can use synthetic biology to achieve directed evolution both in vivo and in vitro. Our talk focused on communication between our audiences, we raised some questions so that everyone could join the discussion. Mainly consisted of how to induce a large mutation library without affecting other genes and how to use synthetic biological methods to accumulate desirable mutants, our talk also expatiated some latest novel research [1-4] in this field, which did give some inspiration to other teams. For example, team member of NWPU said they want to try this method to select a more effective protein for their system.")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Team member of NWPU was talking about selection system in directed evolution")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("The meeting provided a platform for an intense and fruitful exchange of ideas, and we had a wonderful three days together.")])])])}]}},function(e,t,i){i(80);var n=i(14)(i(82),i(83),"data-v-7928d6af",null);e.exports=n.exports},function(e,t,i){var n=i(81);"string"==typeof n&&(n=e.id,n,""),n.locals&&(e.exports=n.locals);i(12)("46642ec3",n,!0)},function(e,t,i){t=e.exports=i(11)(),t.push([e.id,"#labnotes ul[data-v-7928d6af]{list-style:decimal;padding-left:50px;padding-top:10px;margin:10px 0}#labnote ul ul[data-v-7928d6af]{list-style:upper-alpha}#labnotes img[data-v-7928d6af]{margin-top:20px;margin-left:auto;margin-right:auto;display:block}#labnotes hr[data-v-7928d6af]{height:1px;color:#000;border-bottom:1px solid}#labnotes .el-table[data-v-7928d6af]{display:table;margin:10px auto;text-align:center}",""])},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}Object.defineProperty(t,"__esModule",{value:!0});var a=i(16),r=n(a);t.default={data:function(){return{tableData:[{groups:"1. 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summer!")])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Saturday, 8 Apr. 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" BMSCs preparation")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" eight-week old Sprague-Dawley rats (female) weighting 200-250 g(Committee on Animal Care at the School of Life Sciences, Sun Yat-Sen University, China).")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Rats are sacrificed by intraperitoneal (i.p.) injection of 50% chloral hydrate solution (Guangzhou, China);")])]),e._v(" "),i("li",[i("p",[e._v("Sterilize them in 75% ethanol (Guangzhou, China);")])]),e._v(" "),i("li",[i("p",[e._v("Collect the femurs and tibiaes, flushed out bone marrow stromal cells by DMEM/F12 medium (Gibco, Grand Island, NY).")])]),e._v(" "),i("li",[i("p",[e._v("Centrifuged at 200 g for 5 minutes;")])]),e._v(" "),i("li",[i("p",[e._v("Seed cells in DMEM/F12 media with 10% fetal bovine serum (FBS) and 1% Penicillin/Streptomycin (Gibco, Grand Island, NY) at 37℃ incubator with 5% CO2 for 48 hours.")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Monday, 10 Apr. 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" BMSCs collection")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" extracted cells")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Removed the non-adherent cells;")])]),e._v(" "),i("li",[i("p",[e._v("Culture BMSCs to the third passage for further use (change culture medium 3 days each)")])])]),e._v(" "),i("hr"),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" FITC calibration")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" plasmid")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Harvest the cells in the appropriate manner and wash in PBS;")])]),e._v(" "),i("li",[i("p",[e._v("Fix in cold 70% ethanol. Add drop wise to the pellet while vortexing. This should ensure fixation of all cells and minimize clumping;")])]),e._v(" "),i("li",[i("p",[e._v("Fix overnight at 4°C;")])]),e._v(" "),i("li",[i("p",[e._v("Wash 2 X in PBS. Spin at 850 g in a centrifuge and be careful to avoid cell loss when discarding the supernatant especially after spinning out of ethanol.")])]),e._v(" "),i("li",[i("p",[e._v("Treat the cells with ribonuclease. Add 50 µl of a 100 µg/ml sock of RNase. This will ensure only DNA, not RNA, is stained.")])]),e._v(" "),i("li",[i("p",[e._v("Add 200 µl PI (from 50 µg/ml stock solution);")])]),e._v(" "),i("li",[i("p",[e._v("Measure the forward scatter (FS) and side scatter (SS) to identify single cells;")])]),e._v(" "),i("li",[i("p",[e._v("Pulse processing is used to exclude cell doublets from the analysis. 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Centrifuge 5 min at 200 × g, room temperature;")])]),e._v(" "),i("li",[i("p",[e._v("Remove supernatant and add 1 ml of 4°C freezing medium. Resuspend pellet")])]),e._v(" "),i("li",[i("p",[e._v("Pipet 1 ml aliquots of cell suspension into labeled 2-ml cryovials. Tighten caps on vials;")])]),e._v(" "),i("li",[i("p",[e._v("Place vials 1 hour to overnight in a -70℃ freezer, then transfer to liquid nitrogen storage freezer.")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Saturday, 15 Apr. 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" PF-127 preparation")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Liu Xinyi")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" PF-127")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Dissolve PF-127 in DMEM/F12 at 4℃ overnight to prepare 20% (w/v) solution;")])]),e._v(" "),i("li",[i("p",[e._v("Filtered the solution was through a 0.45 μM filter (Millipore, Billerica, MA);")])]),e._v(" "),i("li",[i("p",[e._v("Kept at 4℃ for use;")])]),e._v(" "),i("li",[i("p",[e._v("Dissolve 40% (w/v) PF-127 into 5% (w/v), 10% (w/v), 15% (w/v), 20% (w/v), 25% (w/v), 30% (w/v), 35% (w/v), 40% (w/v);")])]),e._v(" "),i("li",[i("p",[e._v("Separate each 100μl into 1.5ml EP tube. 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")])]),e._v(" "),i("li",[i("p",[e._v("1)\tCell grow for 3 day and 7 day after seeding.")])])])]); },function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Tuesday, 16 May 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" FACS test")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Liu Xinyi")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" BMSCs seeded 3 days ago")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Adding 10% CCK to each well Cell;")])]),e._v(" "),i("li",[i("p",[e._v("Incubated for 2 hours before measuring the absorbance at 450 nM using a microplate reader (VICTORTM X5, PerkinElmer, Waltham, MA).")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Saturday, 20 May 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" FACS test")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Liu Xinyi")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" BMSCs seeded 7 days ago")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Adding 10% CCK to each well Cell;")])]),e._v(" "),i("li",[i("p",[e._v("Incubated for 2 hours before measuring the absorbance at 450 nM using a microplate reader (VICTORTM X5, PerkinElmer, Waltham, MA).")])])]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}})])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Saturday, 3 June 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Cell apoptosis assay")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" BMSCs")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("TansDetect Annexin V-FITC/PI Apoptosis Detection Kit (TransGen Biotech, Beijing, China) was used to evaluate cellular apoptosis according to manufacturer’s instructions;")])]),e._v(" "),i("li",[i("p",[e._v("BMSCs were seeded at a density of 5×105/mL with different encapsulation conditions for 3 days and 7 days.")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Tuesday, 6 June 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Cell apoptosis assay")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" BMSCs seeded 3 days ago")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("The cells were trypsinized and suspended in binding buffer;")])]),e._v(" "),i("li",[i("p",[e._v("Iabeled with 5 μL Annexin V-FITC and 5 μL PI for 15 minutes in the dark on ice;")])]),e._v(" "),i("li",[i("p",[e._v("Add 300 μL binding buffer to each sample;")])]),e._v(" "),i("li",[i("p",[e._v("Evaluate the cells by flow cytometer. 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(Positive control was carried out using 100 μM H2O2 treated for 15 minutes.")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Saturday, 24 June 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Wound healing assay")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" BMSCs")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("HEK293T cells were plated on a 48-well plate and were incubated in DMEM + 10% FBS at 37 ℃ with 5% of CO2.for 24h;")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Sunday, 25 June 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Wound healing assay")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" BMSCs")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Artificial wounds were created by scraping on the cell monolayer with a 10 μL pipette tip;")])]),e._v(" "),i("li",[i("p",[e._v("Debris and floating cells were washed with 1x PBS;")])]),e._v(" "),i("li",[i("p",[e._v("Culture supernatants from our eBMSCs were added;")])]),e._v(" "),i("li",[i("p",[e._v("Images of wounds were captured under light microscopy.")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Monday, 26 June 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Wound healing assay imaging and analysis")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" BMSCs")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("24 h later, the wounds were imaged;")])]),e._v(" "),i("li",[i("p",[e._v("Images were processed with image.J software. For measuring wound healing, the detailed procedure is: enhance contrast -> find edges -> convert to 8-bit -> adjust threshold -> measure. ")])]),e._v(" "),i("li",[i("p",[e._v("For evaluation of cell migration velocity, 20 different in each experimental group were ranked marked manually. The migration distance was measured and the velocity was calculated as distance/time;")])])]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}})])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Thursday, 6 July 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" ELISA assay")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Yang Huan")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" BMSCs (105/mL) in 24-well plates")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Seed BMSCs with different encapsulation conditions for 3 days;")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Sunday, 9 July 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" ELISA assay")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter: Yang Huan")])]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" BMSCs 3 days ago")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Harvest the culture supernatants;")])]),e._v(" "),i("li",[i("p",[e._v("Rat HGF, IGF, EGF, IL-10, IL-6 and TNF-α were measured by using commercial ELISA Kits (Boster, Wuhan, China) according to the manufacturers’ instructions;")])]),e._v(" "),i("li",[i("p",[e._v("Rat IUA model and BMSC transplantation Rat uterine cavity adhesion model was established using mechanical damage method;")])]),e._v(" "),i("li",[i("p",[e._v("Rats were anesthetized with 10% chloral hydrate (300 mg/kg);")])]),e._v(" "),i("li",[i("p",[e._v("The abdominal cavity was opened to expose the uterus;")])]),e._v(" "),i("li",[i("p",[e._v("A 2 mm transverse incision in the left uterus was prepared at the upper end;")])]),e._v(" "),i("li",[i("p",[e._v("A 1.5- 2.0 cm rough-feeling endometrial damage was generated by a scraping spoon;")])]),e._v(" "),i("li",[i("p",[e._v("In the BMSC transplantation test, 200 μL PF-127 encapsulated BMSCs with Vc or other controls was injected into the uterine horn while establishing the IUA;")])]),e._v(" "),i("li",[i("p",[e._v("Rat abdomen was sutured;")])]),e._v(" "),i("li",[i("p",[e._v("Rat was recovered for two weeks followed by further examination. (The right side uterine without damage was considered as sham control).")])])]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}})])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Monday, 10 July 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Preparation of Competent E. Coli Cells")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mao Zeren")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" E. Coli")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Take one colony and start a 5 ml overnight culture at 37°C, with shaking.")])]),e._v(" "),i("li",[i("p",[e._v("Dilute the overnight culture 1:100 into 50 ml SOB medium")])]),e._v(" "),i("li",[i("p",[e._v("Grow culture at 37°C with shaking to an OD600=0.4")])]),e._v(" "),i("li",[i("p",[e._v("Let the culture sit on ice for ~15 min, swirling occasionally")])]),e._v(" "),i("li",[i("p",[e._v("Pour the culture into a 50 ml Falcon™ tube")])]),e._v(" "),i("li",[i("p",[e._v("Centrifuge at 3500 rpm for 5 min at 4°C")])]),e._v(" "),i("li",[i("p",[e._v("Remove as much as possible of the supernatant without disturbing the pellet")])]),e._v(" "),i("li",[i("p",[e._v("Resuspend the pellet in 100 μL ice-cold 0.1 M CaCl2 with the help of a sterilized loop")])]),e._v(" "),i("li",[i("p",[e._v("Add 15 ml ice-cold 0.1 M CaCl2. Mix gently by pipetting up and down a few times")])]),e._v(" "),i("li",[i("p",[e._v("Incubate the cells on ice for 30 min")])]),e._v(" "),i("li",[i("p",[e._v("Pellet the cells again at 3500 rpm for 5 min at 4°C")])]),e._v(" "),i("li",[i("p",[e._v("Resuspend the cells in 2 ml ice-cold 0.1 M CaCl2/20% glycerol")])]),e._v(" "),i("li",[i("p",[e._v("Incubate for 45 min on ice")])]),e._v(" "),i("li",[i("p",[e._v("Aliquot carefully in 50 μL amounts to chilled 1.5 ml tubes")])]),e._v(" "),i("li",[i("p",[e._v("Snap freeze in liquid nitrogen any tubes that will not be used for transformation within a few hours")])]),e._v(" "),i("li",[i("p",[e._v("Store at -80℃")])]),e._v(" "),i("li",[i("p",[e._v("Refer to OMEGA Plasmid Mini Kit I (Cat. D6943-02), store in -20℃.")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Wednesday, 12 July 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" PCR (for adding prefix and suffix)")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mao Zeren")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" DNA templat")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Add the reaction mixture:")]),e._v(" "),i("ul",[i("li",[i("p",[e._v("DNA template: 200-300 ng/50ul (1 ul or 0.5 ul according to template concentration)")])]),e._v(" "),i("li",[i("p",[e._v("Forward primer: 20 pmol (2 ul)")])]),e._v(" "),i("li",[i("p",[e._v("Reverse primer: 20 pmol (2 ul)")])]),e._v(" "),i("li",[i("p",[e._v("PrimeSTAR Max Premix（2×）: 25 ul")])]),e._v(" "),i("li",[i("p",[e._v("DdH2O: up to 50 ul")])])])]),e._v(" "),i("li",[i("p",[e._v("Set-up the reaction condition set-up:")]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Pre-denaturalization: 98℃ for 3minutes")])]),e._v(" "),i("li",[i("p",[e._v("Amplification cycles: 95 ℃ for 30 seconds")])]),e._v(" "),i("li",[i("p",[e._v("68 ℃ for 60 seconds")])]),e._v(" "),i("li",[i("p",[e._v("Repeat for 30 cycles")])]),e._v(" "),i("li",[i("p",[e._v("Final elongation: 72℃ for 3 minutes")])])])])]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Note:")]),e._v(" Primers")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("VEGF-A121 prefix: 5’ CGGAATTCGCGGCCGCTTCTAGATGAACTTTCTGCTGTCTTGGGT 3’"),i("br"),e._v("VEGF-A121 suffix: 5’ AACTGCAGCGGCCGCTACTAGTACCGCCTCGGCTTGTCAC 3’")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("PDGFA prefix: 5’ CGGAATTCGCGGCCGCTTCTAGATGAGGACCTTGGCTTGCCT 3’"),i("br"),e._v("PDGFA suffix: 5’ AACTGCAGCGGCCGCTACTAGTACCTCACATCCGTGTCCTCTTCC 3’")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("bFGF prefix: 5’ CGGAATTCGCGGCCGCTTCTAGACCATGGCAGCCGGGA 3’"),i("br"),e._v("bFGF suffix: 5’ AACTGCAGCGGCCGCTACTAGTAGATCCCGTTGCAACCGC 3’")]),e._v(" "),i("hr"),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" PCR (for gel analysis)")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mao Zeren")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" DNA templat")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Add the reaction mixture:")]),e._v(" "),i("ul",[i("li",[i("p",[e._v("DNA template: 2-3ng/20ul (dilute 1 ul in 49 ul of ddH2O, use 1 ul as template)")])]),e._v(" "),i("li",[i("p",[e._v("Forward primer: 10pmol (1 ul)")])]),e._v(" "),i("li",[i("p",[e._v("Reverse primer: 10pmol (1 ul)")])]),e._v(" "),i("li",[i("p",[e._v("PrimeSTAR Max Premix（2×）: 10 ul")])]),e._v(" "),i("li",[i("p",[e._v("DdH2O: up to 20 ul")])])])]),e._v(" "),i("li",[i("p",[e._v("Set-up the reaction condition set-up:")]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Pre-denaturalization: 98℃ for 3 minutes")])]),e._v(" "),i("li",[i("p",[e._v("Amplification cycles: 95 ℃ for 30 seconds")])]),e._v(" "),i("li",[i("p",[e._v("55 ℃ for 30 seconds")])]),e._v(" "),i("li",[i("p",[e._v("72 ℃ for 10 seconds")])]),e._v(" "),i("li",[i("p",[e._v("Repeat for 30 cycles")])]),e._v(" "),i("li",[i("p",[e._v("Final elongation: 72℃ for 3 minutes")])])])])]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Note:")]),e._v(" Primers")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Forward primer for sequencing/amplifying BioBrick parts (VF2): "),i("br"),e._v("5’ TGCCACCTGACGTCTAAGAA 3’")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Reverse primer for sequencing/amplifying BioBrick parts (VR): "),i("br"),e._v("5’ ATTACCGCCTTTGAGTGAGC 3’")])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Thursday, 13 July 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Plasmid digestion")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mao Zeren")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" plasmid")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Make three mixes: contains 500 ng of one of the three plasmids and ddH2O to 43 μL")])]),e._v(" "),i("li",[i("p",[e._v("To each mix, add 5 μL of 10x reaction buffer for restriction enzymes")])]),e._v(" "),i("li",[i("p",[e._v("Add 1 μL each of the appropriate endonucleases (two per tube) to give a final volume of 50 μL")])]),e._v(" "),i("li",[i("p",[e._v("Tap on the tubes to mix. If necessary, centrifuge for a few seconds to spin down the liquid")])]),e._v(" "),i("li",[i("p",[e._v("Incubate at 37°C for 30 min")])]),e._v(" "),i("li",[i("p",[e._v("Heat-inactivate the enzymes by incubating at 80°C for 20 min")])]),e._v(" "),i("li",[i("p",[e._v("Gel Preparation")]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Close the ends of the gel tray")])]),e._v(" "),i("li",[i("p",[e._v("Insert the comb into the gel tray at one end ~1 cm from the edge")])]),e._v(" "),i("li",[i("p",[e._v("For a 1% 50 ml agarose gel, weigh 0.5 g of agarose in a 100 ml conical flask. Add 50 ml 1x TBE buffer")])]),e._v(" "),i("li",[i("p",[e._v("To dissolve the agarose in the buffer, swirl to mix and microwave for a few minutes taking care not to boil the solution out of the flask. Remove the flask occasionally and check whether the agarose has dissolved completely")])]),e._v(" "),i("li",[i("p",[e._v("Let the agarose solution cool down. Once the solution is touchable, add the DNA stain. Check the stock concentration and add the appropriate amount to give the desired final concentration")])]),e._v(" "),i("li",[i("p",[e._v("Pour the gel solution into the gel tray. Remove any air bubbles with a pipette tip. Put in comb")])]),e._v(" "),i("li",[i("p",[e._v("Wait for the gel to solidify while cooling down to room temperature")])])])]),e._v(" "),i("li",[i("p",[e._v("Release the gel tray from the tape or casting stand. Place the gel tray into the buffer chamber and remove the comb carefully")])]),e._v(" "),i("li",[i("p",[e._v("Add 1x TBE buffer until the gel is completely covered")])]),e._v(" "),i("li",[i("p",[e._v("Take part of DNA samples and mix with loading dye")])]),e._v(" "),i("li",[i("p",[e._v("Load the size marker mixed in 1x loading dye into a well")])]),e._v(" "),i("li",[i("p",[e._v("Load samples into the other wells while writing down which lanes have which samples")])]),e._v(" "),i("li",[i("p",[e._v("Put the lid onto the buffer chamber and connect it to the power supply.")])]),e._v(" "),i("li",[i("p",[e._v("Run the gel at 120 V for 30 min")])]),e._v(" "),i("li",[i("p",[e._v("Stop the run and bring the gel to a UV table to visualize the gel bands")])]),e._v(" "),i("li",[i("p",[e._v("Take a picture of the gel, cut target down")])]),e._v(" "),i("li",[i("p",[e._v("Extract gel refers to OMEGA Gel Extract Kit (Cat. D2500-02).")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Friday, 14 July 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Gene ligation")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mao Zeren")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" digestion mixtures")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Add 2 μL (20 ng) of digestion mixtures to 11 μL of water")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Add 2 μL 10x reaction buffer for T4 DNA ligase")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Add 1 μL of T4 DNA ligase to give a final volume of 20 μL")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Incubate at room temperature (~22°C) for 30 min")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Heat-inactivate the enzymes by heating at 80°C for 20 min")]),e._v(" "),i("hr"),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Transformation")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mao Zeren")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" plasmid")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Turn on a water bath or heating block to 42°C")])]),e._v(" "),i("li",[i("p",[e._v("Thaw competent cells on ice for 15 min")])]),e._v(" "),i("li",[i("p",[e._v("Add 5 μL of ligation reaction mixture or controls above to 50 μL of competent cells")])]),e._v(" "),i("li",[i("p",[e._v("Incubate for 30 min on ice")])]),e._v(" "),i("li",[i("p",[e._v("Heat shock for 45 s at 42°C")])]),e._v(" "),i("li",[i("p",[e._v("Incubate for 5 min on ice")])]),e._v(" "),i("li",[i("p",[e._v("Add 950 μL of SOB media (pre-heated to 37°C).")])]),e._v(" "),i("li",[i("p",[e._v("Incubate for 1–1.5 hr at 37°C, with occasional gentle mixing by inversion of the tubes")])]),e._v(" "),i("li",[i("p",[e._v("For positive controls, mix gently and plate 100 μL only (=1/10th) on an agar plate containing the appropriate antibiotic as in Step 12")])]),e._v(" "),i("li",[i("p",[e._v("Spin cells down from remaining 900 μL at 4000 rpm for 5 min")])]),e._v(" "),i("li",[i("p",[e._v("Discard all but 100 μL of the supernatant and resuspend the pellet in remaining 100 μL")])]),e._v(" "),i("li",[i("p",[e._v("Spread the remaining suspension on an agar plate containing the appropriate antibiotic as follows:")]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Dip the spreader into 95% ethanol")])]),e._v(" "),i("li",[i("p",[e._v("Put it into the flame for a second")])]),e._v(" "),i("li",[i("p",[e._v("Let the ethanol burn off outside the flame")])]),e._v(" "),i("li",[i("p",[e._v("Spread the bacterial suspension evenly out on an agar plate. Continue until all the inoculum has gone into the agar")])]),e._v(" "),i("li",[i("p",[e._v("Put the plates at 37°C overnight")])])])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Friday, 21 July 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Histological analysis")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter: Yang Huan")])]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" surgeried rats")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("The rats were sacrificed and the tissues underwent standard paraffin embedding, section cutting and HE staining")])]),e._v(" "),i("li",[i("p",[e._v("The morphological changes were observed under the light microscope")])]),e._v(" "),i("li",[i("p",[e._v("Image Pro-Plus 6.0 (IPP 6.0) was applied to analyze the thickness of endometrium, the total number of the endometrial glands and the area of interstitial fibrosis of the endometrium")])]),e._v(" "),i("li",[i("p",[e._v("Endometrial fibrosis was revealed by Masson’s trichrome staining")])])]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}})])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Saturday, 22 July 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Histological analysis")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter: Yang Huan")])]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" standard paraffin embedding tissues")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Prepare 4 μM serial sections")])]),e._v(" "),i("li",[i("p",[e._v("Sections were immune-labeled with anti-interleukin-1β antibody (IL-1β, 1:150, rabbit, Bioss, Beijing, China), anti-Pan Cytokeratin antibody (Pan Cytokeratin, 1:50, mouse, Boster, Wuhan, China) and anti-von Willebrand factor antibody (vWF, 1:70, mouse, Boster, Wuhan, China)")])]),e._v(" "),i("li",[i("p",[e._v("Percentages of positive staining area were quantified using the Image-Pro Plus software (Media Cybernetics, Rockville, MD)")])])]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}})])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Thursday, 27 July 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Statistical analyses")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter: Mu Zekun")])]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" data collected before")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Multiple group comparisons were determined by One-way ANOVA followed by Bonferroni’s post-test (*p<0.05, **p<0.01, ***p<0.001). Histological measurement difference was determined by Student’s t-test. p<0.05 was considered statistically significant (*p < 0.05, **p<0.01, ***p<0.001)")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Wednesday, 2 Aug. 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" OD600 Reference Point (Interlab)")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mao Xiaowen, Tao Yu")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" plasmid")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Turn off the path-length correction")])]),e._v(" "),i("li",[i("p",[e._v("Self-testing of instrument")])]),e._v(" "),i("li",[i("p",[e._v("Prepare your 96 well plate")])]),e._v(" "),i("li",[i("p",[e._v("Add 100 μl LUDOX 100 % into wells A1, B1, C1, D1")])]),e._v(" "),i("li",[i("p",[e._v("Add 100 μl of H2O into A2, B2, C2, D2")])]),e._v(" "),i("li",[i("p",[e._v("Measure absorbance 600 nm of all samples in all standard measurement modes in instrument")])]),e._v(" "),i("li",[i("p",[e._v('Import data into "Abs600" blue cells in provided Excel calibration sheet.(Flashes of per well: 10, Orbit averaging: not applied to our instrument, temperature: 37°C)')])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Friday, 4 Aug. 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" FITC calibration (Interlab)")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mao Xiaowen, Tao Yu")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" plasmid")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Turn off the path-length correction")])]),e._v(" "),i("li",[i("p",[e._v("Self-testing of instrument")])]),e._v(" "),i("li",[i("p",[e._v("Set the gain to 60%")])]),e._v(" "),i("li",[i("p",[e._v("Set the excitation wavelength to 480nm")])]),e._v(" "),i("li",[i("p",[e._v("Set the emission wavelength to 509nm")])]),e._v(" "),i("li",[i("p",[e._v("Set the model to top optic fluorescence reading")])]),e._v(" "),i("li",[i("p",[e._v("Prepare your 96 well plate")])]),e._v(" "),i("li",[i("p",[e._v("Spin down FITC stock tube to make sure pellet is at the bottom of tube")])]),e._v(" "),i("li",[i("p",[e._v("Prepare 2x FITC stock solution (500 μM) by resuspending FITC in 1ml of 1x Phosphate Buffer Saline (PBS)")])]),e._v(" "),i("li",[i("p",[e._v("1)\tIncubate the solution at 42°C for 4 hours. Properly dissolved FITC."),i("br"),e._v("(To check this after the incubation period pipetted up and down – if any particulates are visible in the pipette tip continue to incubate overnight.)")])]),e._v(" "),i("li",[i("p",[e._v("Dilute the 2x FITC stock solution in half to make a 1x FITC solution (final concentration is 250 μM).")])]),e._v(" "),i("li",[i("p",[e._v("Add 100 μl of PBS into wells A2, B2, C2, D2....A12, B12, C12, D12")])]),e._v(" "),i("li",[i("p",[e._v("Add 200 μl of FITC stock solution into A1, B1, C1, D1")])]),e._v(" "),i("li",[i("p",[e._v("Transfer 100 μl of FITC stock solution from A1 into A2")])]),e._v(" "),i("li",[i("p",[e._v("Mix A2 by pipetting up and down 3x and transfer 100 μl into A3"),i("br"),e._v("Mix A3 by pipetting up and down 3x and transfer 100 μl into A4"),i("br"),e._v("Mix A4 by pipetting up and down 3x and transfer 100 μl into A5"),i("br"),e._v("\n Mix A5 by pipetting up and down 3x and transfer 100 μl into A6"),i("br"),e._v("Mix A6 by pipetting up and down 3x and transfer 100 μl into A7"),i("br"),e._v("Mix A7 by pipetting up and down 3x and transfer 100 μl into A8"),i("br"),e._v("Mix A8 by pipetting up and down 3x and transfer 100 μl into A9"),i("br"),e._v("Mix A9 by pipetting up and down 3x and transfer 100 μl into A10"),i("br"),e._v("Mix A10 by pipetting up and down 3x and transfer 100 μl into A11"),i("br"),e._v("\n Mix A11 by pipetting up and down 3x and transfer 100 μl into liquid waste"),i("br"),e._v("(TAKE CARE NOT TO CONTINUE SERIAL DILUTION INTO COLUMN 12.)")])]),e._v(" "),i("li",[i("p",[e._v("Repeat dilution series for rows B, C, D")])]),e._v(" "),i("li",[i("p",[e._v("Measure fluorescence of all samples in all standard measurement modes in instrument")])]),e._v(" "),i("li",[i("p",[e._v("Measure fluorescence of all of your samples")])]),e._v(" "),i("li",[i("p",[e._v('Import data into "Fluorescence" blue cells in provided Excel calibration sheet.'),i("br"),e._v("(Flashes of per well: 10, Orbit averaging: not applied to our instrument, temperature: 37 ℃)")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Friday, 18 Aug. 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Cell preparation for transient transfection")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" BMSCs")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("plate 0.5-2 x 105 cells in 500 μl of growth medium without antibiotics for 24h")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Saturday, 19 Aug. 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Transient transfection")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" BMSCs")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Prepare complexes as follows for each plate:")]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Dilute DNA in 50 μl of Opti-MEM® I Reduced Serum Medium without serum (or other medium without serum). Mix gently.")])]),e._v(" "),i("li",[i("p",[e._v("Mix Lipofectamine® 2000 gently before use, then dilute the appropriate amount in 50 μl of Opti-MEM® I Medium. Incubate for 5 minutes at room temperature. Note: Proceed to Step c within 25 minutes.")])]),e._v(" "),i("li",[i("p",[e._v("After the 5 minute incubation, combine the diluted DNA with diluted Lipofectamine® 2000 (total volume = 100 μl). Mix gently and incubate for 20 minutes at room temperature (solution may appear cloudy). Note: Complexes are stable for 6 hours at room temperature.")])])])]),e._v(" "),i("li",[i("p",[e._v("Add the 100 μl of complexes to each well containing cells and medium. Mix gently by rocking the plate back and forth.")])]),e._v(" "),i("li",[i("p",[e._v("Incubate cells at 37°C in a CO2 incubator for 18-48 hours prior to testing for transgene expression. Medium may be changed after 6-8 hours.")])])])]); },function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Saturday, 19 Aug. 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Transient transfection")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" transfected BMSCs")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Medium change.")])])]),e._v(" "),i("hr"),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Lentivirus production and infection")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" BMSCs")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Plate 0.5-2 x 105 cells in 500 μl of growth medium without antibiotics so that cells will be 40-70% confluent at the time of transfection.")])]),e._v(" "),i("li",[i("p",[e._v("Transfection mix")]),e._v(" "),i("ul",[i("li",[i("p",[e._v("In each sterile 1.5 ml tube, dilute 500 ng pMD2.G, 1 μg pSPAX2, and 2μg of pCDH expression plasmid DNA in 200 μ l of opti-MEM. Mix gently.")])]),e._v(" "),i("li",[i("p",[e._v("In other sterile 1.5 ml tube, dilute 2 μl Lipofectamine™ 2000 (mix gently before use) in 200μ l of opti-MEM. Mix gently and incubate for 5 minutes at room temperature.")])]),e._v(" "),i("li",[i("p",[e._v("After incubation, combine the diluted DNA (Step a) with the diluted Lipofectamine™ 2000 (Step b). Mix gently.")])]),e._v(" "),i("li",[i("p",[e._v("Incubate for 15 minutes at room temperature to allow the DNALipo2000 complexes to form.")])]),e._v(" "),i("li",[i("p",[e._v("Add the complex to each HEK293T cell plate well.")])]),e._v(" "),i("li",[i("p",[e._v("Remove and discard the medium and replace with 2ml DMEM. Incubate cells 48hours at37°C in a humidified 5% CO2 incubator.")])])])]),e._v(" "),i("li",[i("p",[e._v("Set up the target cell line in target cell medium to 6 well plate so that they will be 30% confluent on the next day.")])]),e._v(" "),i("li",[i("p",[e._v("Post-transfection")]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Harvest virus-containing supernatants and filter the viral supernatants through a 0.45 μm filter in 15 ml sterile tube")])]),e._v(" "),i("li",[i("p",[e._v("Infect target cells: 1 volume of DMEM (2ml) and 1 volume of filtered virus-containing supernatants (2ml), with 4 μl polybrene (8mg/ml)")])]),e._v(" "),i("li",[i("p",[e._v("Select cells by 1 μg/mL of puromycin to screen for stably-transfected BMSCs")])])])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Tuesday, 22 Aug. 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Lentivirus infection (second time)")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" BMSCs, infected two days ago")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Post-transfection:")]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Harvest virus-containing supernatants and filter the viral supernatants through a 0.45 μm filter in 15 ml sterile tube.")])]),e._v(" "),i("li",[i("p",[e._v("Infect target cells: 1 volume of DMEM (2ml) and 1 volume of filtered virus-containing supernatants (2ml), with 4 μl polybrene (8mg/ml).")])])])]),e._v(" "),i("li",[i("p",[e._v("Select cells by 1 μg/mL of puromycin to screen for stably-transfected BMSCs.")])]),e._v(" "),i("li",[i("p",[e._v("Store in -80℃.")])])])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Tuesday, 12 Sept. 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" RNA Extraction and Reverse Transcription")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v(" Mu Zekun")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" cells")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Wash cells with PBS. Prepare cell suspension using Trypsin-EDTA.")])]),e._v(" "),i("li",[i("p",[e._v("Centrifuge at 1,000 rpm for 2 min, remove supernatant.")])]),e._v(" "),i("li",[i("p",[e._v("Add 1ml Trizol, mix by pipetting up and down a few times.")])]),e._v(" "),i("li",[i("p",[e._v("Add 0.2ml of chloroform, shake vigorously then allow to stand for a few minutes until phase start to separate.")])]),e._v(" "),i("li",[i("p",[e._v("Centrifuge at 13,000 g for 15min at 4°C.")])]),e._v(" "),i("li",[i("p",[e._v("Transfer the colorless upper phase to a new clean tube, avoiding the white interphase.")])]),e._v(" "),i("li",[i("p",[e._v("Add 0.6ml of isopropanol, mix by inverting the tube several times gently.")])]),e._v(" "),i("li",[i("p",[e._v("Centrifuge at 13,000 g for 10min at 4°C.")])]),e._v(" "),i("li",[i("p",[e._v("Remove supernatant and wash RNA by adding 0.7ml of 75% ethanol.")])]),e._v(" "),i("li",[i("p",[e._v("Repeat step 8 and 9.")])]),e._v(" "),i("li",[i("p",[e._v("Centrifuge at 13,000 g for 10min at 4°C, remove supernatant and invert the tube on a clean kimwipe.")])]),e._v(" "),i("li",[i("p",[e._v("Wait for pellet to dry.")])]),e._v(" "),i("li",[i("p",[e._v("Resuspend pellet with DEPC water.")])]),e._v(" "),i("li",[i("p",[e._v("PrimeScript™ 1st Strand cDNA Synthesis Kit (Cat. 6110A) is use d for reverse transcription."),i("br"),e._v("Protocol refers to instruction of the kit.")])]),e._v(" "),i("li",[i("p",[e._v("Run in gel for 10min with 150V, take picture under ultraviolet light.")])]),e._v(" "),i("li",[i("p",[e._v("Analyzed growth factor overexpression with Image J.")])])]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}})])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Monday, 18 Sept. 2017")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Purpose:")]),e._v(" Sample preparation")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Experimenter:")]),e._v("Mao Zeren")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Samples:")]),e._v(" cell")]),e._v(" "),i("p",{staticClass:"card-text"},[i("strong",[e._v("Steps:")])]),e._v(" "),i("ul",[i("li",[i("p",[e._v("Place the cell culture dish on ice and wash the cells with ice-cold PBS.")])]),e._v(" "),i("li",[i("p",[e._v("Aspirate the PBS, then add ice-cold lysis buffer (1 mL per 107 cells/100 mm dish/150 cm2 flask; 0.5 mL per 5x106 cells/60 mm dish/75 cm2 flask).")])]),e._v(" "),i("li",[i("p",[e._v("Scrape adherent cells off the dish using a cold plastic cell scraper, then gently transfer the cell suspension into a pre-cooled microcentrifuge tube. 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r.setLineWidth:this.setLineWidth(s[0]);break;case r.setLineJoin:this.setLineJoin(s[0]);break;case r.setLineCap:this.setLineCap(s[0]);break;case r.setMiterLimit:this.setMiterLimit(s[0]);break;case r.setFillRGBColor:this.setFillRGBColor(s[0],s[1],s[2]);break;case r.setStrokeRGBColor:this.setStrokeRGBColor(s[0],s[1],s[2]);break;case r.setDash:this.setDash(s[0],s[1]);break;case r.setGState:this.setGState(s[0]);break;case r.fill:this.fill();break;case r.eoFill:this.eoFill();break;case r.stroke:this.stroke();break;case r.fillStroke:this.fillStroke();break;case r.eoFillStroke:this.eoFillStroke();break;case r.clip:this.clip("nonzero");break;case r.eoClip:this.clip("evenodd");break;case r.paintSolidColorImageMask:this.paintSolidColorImageMask();break;case r.paintJpegXObject:this.paintJpegXObject(s[0],s[1],s[2]);break;case r.paintImageXObject:this.paintImageXObject(s[0]);break;case r.paintInlineImageXObject:this.paintInlineImageXObject(s[0]);break;case r.paintImageMaskXObject:this.paintImageMaskXObject(s[0]);break;case r.paintFormXObjectBegin:this.paintFormXObjectBegin(s[0],s[1]);break;case r.paintFormXObjectEnd:this.paintFormXObjectEnd();break;case r.closePath:this.closePath();break;case r.closeStroke:this.closeStroke();break;case r.closeFillStroke:this.closeFillStroke();break;case r.nextLine:this.nextLine();break;case r.transform:this.transform(s[0],s[1],s[2],s[3],s[4],s[5]);break;case r.constructPath:this.constructPath(s[0],s[1]);break;case r.endPath:this.endPath();break;case 92:this.group(e[i].items);break;default:c("Unimplemented method "+n)}}},setWordSpacing:function(e){this.current.wordSpacing=e},setCharSpacing:function(e){this.current.charSpacing=e},nextLine:function(){this.moveText(0,this.current.leading)},setTextMatrix:function(e,t,i,n,r,s){var o=this.current;this.current.textMatrix=this.current.lineMatrix=[e,t,i,n,r,s],this.current.x=this.current.lineX=0,this.current.y=this.current.lineY=0,o.xcoords=[],o.tspan=document.createElementNS(v,"svg:tspan"),o.tspan.setAttributeNS(null,"font-family",o.fontFamily),o.tspan.setAttributeNS(null,"font-size",a(o.fontSize)+"px"),o.tspan.setAttributeNS(null,"y",a(-o.y)),o.txtElement=document.createElementNS(v,"svg:text"),o.txtElement.appendChild(o.tspan)},beginText:function(){this.current.x=this.current.lineX=0,this.current.y=this.current.lineY=0,this.current.textMatrix=n,this.current.lineMatrix=n,this.current.tspan=document.createElementNS(v,"svg:tspan"),this.current.txtElement=document.createElementNS(v,"svg:text"),this.current.txtgrp=document.createElementNS(v,"svg:g"),this.current.xcoords=[]},moveText:function(e,t){var i=this.current;this.current.x=this.current.lineX+=e, 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font-family: "'+e.loadedName+'"; src: url('+t+"); }\n"},setFont:function(e){var t=this.current,n=this.commonObjs.get(e[0]),r=e[1];this.current.font=n,this.embedFonts&&n.data&&!this.embeddedFonts[n.loadedName]&&(this.addFontStyle(n),this.embeddedFonts[n.loadedName]=n),t.fontMatrix=n.fontMatrix?n.fontMatrix:i;var s=n.black?n.bold?"bolder":"bold":n.bold?"bold":"normal",o=n.italic?"italic":"normal";r<0?(r=-r,t.fontDirection=-1):t.fontDirection=1,t.fontSize=r,t.fontFamily=n.loadedName,t.fontWeight=s,t.fontStyle=o,t.tspan=document.createElementNS(v,"svg:tspan"),t.tspan.setAttributeNS(null,"y",a(-t.y)),t.xcoords=[]},endText:function(){this.current.pendingClip?(this.cgrp.appendChild(this.tgrp),this.pgrp.appendChild(this.cgrp)):this.pgrp.appendChild(this.tgrp),this.tgrp=document.createElementNS(v,"svg:g"),this.tgrp.setAttributeNS(null,"transform",p(this.transformMatrix))},setLineWidth:function(e){this.current.lineWidth=e},setLineCap:function(e){this.current.lineCap=b[e]},setLineJoin:function(e){this.current.lineJoin=_[e]},setMiterLimit:function(e){this.current.miterLimit=e},setStrokeRGBColor:function(e,t,i){var n=s.makeCssRgb(e,t,i);this.current.strokeColor=n},setFillRGBColor:function(e,t,i){var n=s.makeCssRgb(e,t,i);this.current.fillColor=n,this.current.tspan=document.createElementNS(v,"svg:tspan"),this.current.xcoords=[]},setDash:function(e,t){this.current.dashArray=e,this.current.dashPhase=t},constructPath:function(e,t){var i=this.current,n=i.x,s=i.y;i.path=document.createElementNS(v,"svg:path");for(var o=[],l=e.length,c=0,u=0;c<l;c++)switch(0|e[c]){case r.rectangle:n=t[u++],s=t[u++];var d=t[u++],h=t[u++],f=n+d,p=s+h;o.push("M",a(n),a(s),"L",a(f),a(s),"L",a(f),a(p),"L",a(n),a(p),"Z");break;case r.moveTo:n=t[u++],s=t[u++],o.push("M",a(n),a(s));break;case r.lineTo:n=t[u++],s=t[u++],o.push("L",a(n),a(s));break;case r.curveTo:n=t[u+4],s=t[u+5],o.push("C",a(t[u]),a(t[u+1]),a(t[u+2]),a(t[u+3]),a(n),a(s)),u+=6;break;case r.curveTo2:n=t[u+2],s=t[u+3],o.push("C",a(n),a(s),a(t[u]),a(t[u+1]),a(t[u+2]),a(t[u+3])),u+=4;break;case r.curveTo3:n=t[u+2],s=t[u+3],o.push("C",a(t[u]),a(t[u+1]),a(n),a(s),a(n),a(s)),u+=4;break;case r.closePath:o.push("Z")}i.path.setAttributeNS(null,"d",o.join(" 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t=this.current;t.clipId="clippath"+x,x++,this.clippath=document.createElementNS(v,"svg:clipPath"),this.clippath.setAttributeNS(null,"id",t.clipId);var i=t.element.cloneNode();"evenodd"===e?i.setAttributeNS(null,"clip-rule","evenodd"):i.setAttributeNS(null,"clip-rule","nonzero"),this.clippath.setAttributeNS(null,"transform",p(this.transformMatrix)),this.clippath.appendChild(i),this.defs.appendChild(this.clippath),t.pendingClip=!0,this.cgrp=document.createElementNS(v,"svg:g"),this.cgrp.setAttributeNS(null,"clip-path","url(#"+t.clipId+")"),this.pgrp.appendChild(this.cgrp)},closePath:function(){var e=this.current,t=e.path.getAttributeNS(null,"d");t+="Z",e.path.setAttributeNS(null,"d",t)},setLeading:function(e){this.current.leading=-e},setTextRise:function(e){this.current.textRise=e},setHScale:function(e){this.current.textHScale=e/100},setGState:function(e){for(var t=0,i=e.length;t<i;t++){var n=e[t],a=n[0],r=n[1];switch(a){case"LW":this.setLineWidth(r);break;case"LC":this.setLineCap(r);break;case"LJ":this.setLineJoin(r);break;case"ML":this.setMiterLimit(r);break;case"D":this.setDash(r[0],r[1]);break;case"RI":break;case"FL":break;case"Font":this.setFont(r);break;case"CA":break;case"ca":break;case"BM":break;case"SMask":}}},fill:function(){var e=this.current;e.element.setAttributeNS(null,"fill",e.fillColor)},stroke:function(){var e=this.current;e.element.setAttributeNS(null,"stroke",e.strokeColor),e.element.setAttributeNS(null,"fill","none")},eoFill:function(){var e=this.current;e.element.setAttributeNS(null,"fill",e.fillColor),e.element.setAttributeNS(null,"fill-rule","evenodd")},fillStroke:function(){this.stroke(),this.fill()},eoFillStroke:function(){this.current.element.setAttributeNS(null,"fill-rule","evenodd"),this.fillStroke()},closeStroke:function(){this.closePath(),this.stroke()},closeFillStroke:function(){this.closePath(),this.fillStroke()},paintSolidColorImageMask:function(){var e=this.current,t=document.createElementNS(v,"svg:rect");t.setAttributeNS(null,"x","0"),t.setAttributeNS(null,"y","0"),t.setAttributeNS(null,"width","1px"),t.setAttributeNS(null,"height","1px"),t.setAttributeNS(null,"fill",e.fillColor),this.tgrp.appendChild(t)},paintJpegXObject:function(e,t,i){var n=this.current,r=this.objs.get(e),s=document.createElementNS(v,"svg:image");s.setAttributeNS(y,"xlink:href",r.src),s.setAttributeNS(null,"width",r.width+"px"),s.setAttributeNS(null,"height",r.height+"px"),s.setAttributeNS(null,"x","0"),s.setAttributeNS(null,"y",a(-i)),s.setAttributeNS(null,"transform","scale("+a(1/t)+" "+a(-1/i)+")"),this.tgrp.appendChild(s),n.pendingClip?(this.cgrp.appendChild(this.tgrp),this.pgrp.appendChild(this.cgrp)):this.pgrp.appendChild(this.tgrp)},paintImageXObject:function(e){var t=this.objs.get(e);return t?void this.paintInlineImageXObject(t):void c("Dependent image isn't ready yet")},paintInlineImageXObject:function(e,t){var i=this.current,n=e.width,r=e.height,s=h(e,this.forceDataSchema),o=document.createElementNS(v,"svg:rect");o.setAttributeNS(null,"x","0"),o.setAttributeNS(null,"y","0"),o.setAttributeNS(null,"width",a(n)),o.setAttributeNS(null,"height",a(r)),i.element=o,this.clip("nonzero");var l=document.createElementNS(v,"svg:image");l.setAttributeNS(y,"xlink:href",s),l.setAttributeNS(null,"x","0"),l.setAttributeNS(null,"y",a(-r)),l.setAttributeNS(null,"width",a(n)+"px"),l.setAttributeNS(null,"height",a(r)+"px"),l.setAttributeNS(null,"transform","scale("+a(1/n)+" "+a(-1/r)+")"),t?t.appendChild(l):this.tgrp.appendChild(l),i.pendingClip?(this.cgrp.appendChild(this.tgrp),this.pgrp.appendChild(this.cgrp)):this.pgrp.appendChild(this.tgrp)},paintImageMaskXObject:function(e){var t=this.current,i=e.width,n=e.height,r=t.fillColor;t.maskId="mask"+C++;var s=document.createElementNS(v,"svg:mask");s.setAttributeNS(null,"id",t.maskId);var o=document.createElementNS(v,"svg:rect");o.setAttributeNS(null,"x","0"),o.setAttributeNS(null,"y","0"),o.setAttributeNS(null,"width",a(i)),o.setAttributeNS(null,"height",a(n)),o.setAttributeNS(null,"fill",r),o.setAttributeNS(null,"mask","url(#"+t.maskId+")"),this.defs.appendChild(s),this.tgrp.appendChild(o),this.paintInlineImageXObject(e,s)},paintFormXObjectBegin:function(e,t){if(this.save(),l(e)&&6===e.length&&this.transform(e[0],e[1],e[2],e[3],e[4],e[5]),l(t)&&4===t.length){var i=t[2]-t[0],n=t[3]-t[1],r=document.createElementNS(v,"svg:rect");r.setAttributeNS(null,"x",t[0]),r.setAttributeNS(null,"y",t[1]),r.setAttributeNS(null,"width",a(i)),r.setAttributeNS(null,"height",a(n)),this.current.element=r,this.clip("nonzero"),this.endPath()}},paintFormXObjectEnd:function(){this.restore()}},m}();e.SVGGraphics=p}),function(e,t){t(e.pdfjsDisplayAnnotationLayer={},e.pdfjsSharedUtil,e.pdfjsDisplayDOMUtils)}(this,function(e,t,i){function n(){}var a=t.AnnotationBorderStyleType,r=t.AnnotationType,s=t.Util,o=i.addLinkAttributes,l=i.LinkTarget,c=i.getFilenameFromUrl,u=t.warn,d=i.CustomStyle,h=i.getDefaultSetting;n.prototype={create:function(e){var t=e.data.annotationType;switch(t){case r.LINK:return new p(e);case r.TEXT:return new m(e);case r.WIDGET:var i=e.data.fieldType;switch(i){case"Tx":return new g(e)}return new v(e);case r.POPUP:return new y(e);case r.HIGHLIGHT:return new _(e);case r.UNDERLINE:return new x(e);case r.SQUIGGLY:return new C(e);case r.STRIKEOUT:return new w(e);case r.FILEATTACHMENT:return new S(e);default:return new f(e)}}};var f=function(){function e(e,t){this.isRenderable=t||!1,this.data=e.data,this.layer=e.layer,this.page=e.page,this.viewport=e.viewport,this.linkService=e.linkService,this.downloadManager=e.downloadManager,this.imageResourcesPath=e.imageResourcesPath,this.renderInteractiveForms=e.renderInteractiveForms,t&&(this.container=this._createContainer())}return e.prototype={_createContainer:function(){var e=this.data,t=this.page,i=this.viewport,n=document.createElement("section"),r=e.rect[2]-e.rect[0],o=e.rect[3]-e.rect[1];n.setAttribute("data-annotation-id",e.id);var l=s.normalizeRect([e.rect[0],t.view[3]-e.rect[1]+t.view[1],e.rect[2],t.view[3]-e.rect[3]+t.view[1]]);if(d.setProp("transform",n,"matrix("+i.transform.join(",")+")"),d.setProp("transformOrigin",n,-l[0]+"px "+-l[1]+"px"),e.borderStyle.width>0){n.style.borderWidth=e.borderStyle.width+"px",e.borderStyle.style!==a.UNDERLINE&&(r-=2*e.borderStyle.width,o-=2*e.borderStyle.width);var c=e.borderStyle.horizontalCornerRadius,h=e.borderStyle.verticalCornerRadius;if(c>0||h>0){var f=c+"px / "+h+"px";d.setProp("borderRadius",n,f)}switch(e.borderStyle.style){case a.SOLID:n.style.borderStyle="solid";break;case a.DASHED:n.style.borderStyle="dashed";break;case a.BEVELED:u("Unimplemented border style: beveled");break;case a.INSET:u("Unimplemented border style: inset");break;case a.UNDERLINE:n.style.borderBottomStyle="solid"}e.color?n.style.borderColor=s.makeCssRgb(0|e.color[0],0|e.color[1],0|e.color[2]):n.style.borderWidth=0}return n.style.left=l[0]+"px",n.style.top=l[1]+"px",n.style.width=r+"px",n.style.height=o+"px",n},_createPopup:function(e,t,i){t||(t=document.createElement("div"),t.style.height=e.style.height,t.style.width=e.style.width,e.appendChild(t));var n=new b({container:e,trigger:t,color:i.color,title:i.title,contents:i.contents,hideWrapper:!0}),a=n.render();a.style.left=e.style.width,e.appendChild(a)},render:function(){throw new Error("Abstract method AnnotationElement.render called")}},e}(),p=function(){function e(e){f.call(this,e,!0)}return s.inherit(e,f,{render:function(){this.container.className="linkAnnotation";var e=document.createElement("a");return o(e,{url:this.data.url,target:this.data.newWindow?l.BLANK:void 0}),this.data.url||(this.data.action?this._bindNamedAction(e,this.data.action):this._bindLink(e,this.data.dest||null)),this.container.appendChild(e),this.container},_bindLink:function(e,t){var i=this;e.href=this.linkService.getDestinationHash(t),e.onclick=function(){return t&&i.linkService.navigateTo(t),!1},t&&(e.className="internalLink")},_bindNamedAction:function(e,t){var i=this;e.href=this.linkService.getAnchorUrl(""),e.onclick=function(){return i.linkService.executeNamedAction(t),!1},e.className="internalLink"}}),e}(),m=function(){function e(e){var t=!!(e.data.hasPopup||e.data.title||e.data.contents);f.call(this,e,t)}return s.inherit(e,f,{render:function(){this.container.className="textAnnotation";var e=document.createElement("img");return e.style.height=this.container.style.height,e.style.width=this.container.style.width,e.src=this.imageResourcesPath+"annotation-"+this.data.name.toLowerCase()+".svg",e.alt="[[[:Template:Type]] Annotation]",e.dataset.l10nId="text_annotation_type",e.dataset.l10nArgs=JSON.stringify({type:this.data.name}),this.data.hasPopup||this._createPopup(this.container,e,this.data),this.container.appendChild(e),this.container}}),e}(),v=function(){function e(e){var t=e.renderInteractiveForms||!e.data.hasAppearance&&!!e.data.fieldValue;f.call(this,e,t)}return s.inherit(e,f,{render:function(){return this.container}}),e}(),g=function(){function e(e){v.call(this,e)}var t=["left","center","right"];return s.inherit(e,v,{render:function(){this.container.className="textWidgetAnnotation";var e=null;if(this.renderInteractiveForms){if(this.data.multiLine?(e=document.createElement("textarea"),e.textContent=this.data.fieldValue):(e=document.createElement("input"),e.type="text",e.setAttribute("value",this.data.fieldValue)),e.disabled=this.data.readOnly,null!==this.data.maxLen&&(e.maxLength=this.data.maxLen),this.data.comb){var i=this.data.rect[2]-this.data.rect[0],n=i/this.data.maxLen;e.classList.add("comb"),e.style.letterSpacing="calc("+n+"px - 1ch)"}}else{e=document.createElement("div"),e.textContent=this.data.fieldValue,e.style.verticalAlign="middle",e.style.display="table-cell";var a=null;this.data.fontRefName&&(a=this.page.commonObjs.getData(this.data.fontRefName)),this._setTextStyle(e,a)}return null!==this.data.textAlignment&&(e.style.textAlign=t[this.data.textAlignment]),this.container.appendChild(e),this.container},_setTextStyle:function(e,t){var i=e.style;if(i.fontSize=this.data.fontSize+"px",i.direction=this.data.fontDirection<0?"rtl":"ltr",t){i.fontWeight=t.black?t.bold?"900":"bold":t.bold?"bold":"normal",i.fontStyle=t.italic?"italic":"normal";var n=t.loadedName?'"'+t.loadedName+'", ':"",a=t.fallbackName||"Helvetica, sans-serif";i.fontFamily=n+a}}}),e}(),y=function(){function e(e){var t=!(!e.data.title&&!e.data.contents);f.call(this,e,t)}return s.inherit(e,f,{render:function(){this.container.className="popupAnnotation";var e='[data-annotation-id="'+this.data.parentId+'"]',t=this.layer.querySelector(e);if(!t)return this.container;var i=new b({container:this.container,trigger:t,color:this.data.color,title:this.data.title,contents:this.data.contents}),n=parseFloat(t.style.left),a=parseFloat(t.style.width);return d.setProp("transformOrigin",this.container,-(n+a)+"px -"+t.style.top),this.container.style.left=n+a+"px",this.container.appendChild(i.render()),this.container}}),e}(),b=function(){function e(e){this.container=e.container,this.trigger=e.trigger,this.color=e.color,this.title=e.title,this.contents=e.contents,this.hideWrapper=e.hideWrapper||!1,this.pinned=!1}var t=.7;return e.prototype={render:function(){var e=document.createElement("div");e.className="popupWrapper",this.hideElement=this.hideWrapper?e:this.container,this.hideElement.setAttribute("hidden",!0);var i=document.createElement("div");i.className="popup";var n=this.color;if(n){var a=t*(255-n[0])+n[0],r=t*(255-n[1])+n[1],o=t*(255-n[2])+n[2];i.style.backgroundColor=s.makeCssRgb(0|a,0|r,0|o)}var l=this._formatContents(this.contents),c=document.createElement("h1");return c.textContent=this.title,this.trigger.addEventListener("click",this._toggle.bind(this)),this.trigger.addEventListener("mouseover",this._show.bind(this,!1)),this.trigger.addEventListener("mouseout",this._hide.bind(this,!1)),i.addEventListener("click",this._hide.bind(this,!0)),i.appendChild(c),i.appendChild(l),e.appendChild(i),e},_formatContents:function(e){for(var t=document.createElement("p"),i=e.split(/(?:\r\n?|\n)/),n=0,a=i.length;n<a;++n){var r=i[n];t.appendChild(document.createTextNode(r)),n<a-1&&t.appendChild(document.createElement("br"))}return t},_toggle:function(){this.pinned?this._hide(!0):this._show(!0)},_show:function(e){e&&(this.pinned=!0),this.hideElement.hasAttribute("hidden")&&(this.hideElement.removeAttribute("hidden"),this.container.style.zIndex+=1)},_hide:function(e){e&&(this.pinned=!1),this.hideElement.hasAttribute("hidden")||this.pinned||(this.hideElement.setAttribute("hidden",!0),this.container.style.zIndex-=1)}},e}(),_=function(){function e(e){var t=!!(e.data.hasPopup||e.data.title||e.data.contents);f.call(this,e,t)}return s.inherit(e,f,{render:function(){return this.container.className="highlightAnnotation",this.data.hasPopup||this._createPopup(this.container,null,this.data),this.container}}),e}(),x=function(){function e(e){var t=!!(e.data.hasPopup||e.data.title||e.data.contents);f.call(this,e,t)}return s.inherit(e,f,{render:function(){return this.container.className="underlineAnnotation",this.data.hasPopup||this._createPopup(this.container,null,this.data),this.container}}),e}(),C=function(){function e(e){var t=!!(e.data.hasPopup||e.data.title||e.data.contents);f.call(this,e,t)}return s.inherit(e,f,{render:function(){return this.container.className="squigglyAnnotation",this.data.hasPopup||this._createPopup(this.container,null,this.data),this.container}}),e}(),w=function(){function e(e){var t=!!(e.data.hasPopup||e.data.title||e.data.contents);f.call(this,e,t)}return s.inherit(e,f,{render:function(){return this.container.className="strikeoutAnnotation",this.data.hasPopup||this._createPopup(this.container,null,this.data),this.container}}),e}(),S=function(){function e(e){f.call(this,e,!0),this.filename=c(e.data.file.filename),this.content=e.data.file.content}return s.inherit(e,f,{render:function(){this.container.className="fileAttachmentAnnotation";var e=document.createElement("div");return e.style.height=this.container.style.height,e.style.width=this.container.style.width,e.addEventListener("dblclick",this._download.bind(this)),this.data.hasPopup||!this.data.title&&!this.data.contents||this._createPopup(this.container,e,this.data),this.container.appendChild(e),this.container},_download:function(){return this.downloadManager?void this.downloadManager.downloadData(this.content,this.filename,""):void u("Download cannot be started due to unavailable download manager")}}),e}(),M=function(){return{render:function(e){for(var t=new n,i=0,a=e.annotations.length;i<a;i++){var r=e.annotations[i];if(r){var s={data:r,layer:e.div,page:e.page,viewport:e.viewport,linkService:e.linkService,downloadManager:e.downloadManager,imageResourcesPath:e.imageResourcesPath||h("imageResourcesPath"),renderInteractiveForms:e.renderInteractiveForms||!1},o=t.create(s);o.isRenderable&&e.div.appendChild(o.render())}}},update:function(e){for(var t=0,i=e.annotations.length;t<i;t++){var n=e.annotations[t],a=e.div.querySelector('[data-annotation-id="'+n.id+'"]');a&&d.setProp("transform",a,"matrix("+e.viewport.transform.join(",")+")")}e.div.removeAttribute("hidden")}}}();e.AnnotationLayer=M}),function(e,t){t(e.pdfjsDisplayTextLayer={},e.pdfjsSharedUtil,e.pdfjsDisplayDOMUtils)}(this,function(e,t,i){var n=t.Util,a=t.createPromiseCapability,r=i.CustomStyle,s=i.getDefaultSetting,o=function(){function e(e){return!f.test(e)}function t(t,i,a){var r=document.createElement("div"),o={style:null,angle:0,canvasWidth:0,isWhitespace:!1,originalTransform:null,paddingBottom:0,paddingLeft:0,paddingRight:0,paddingTop:0,scale:1};if(t._textDivs.push(r),e(i.str))return o.isWhitespace=!0,void t._textDivProperties.set(r,o);var l=n.transform(t._viewport.transform,i.transform),c=Math.atan2(l[1],l[0]),u=a[i.fontName];u.vertical&&(c+=Math.PI/2);var d=Math.sqrt(l[2]*l[2]+l[3]*l[3]),h=d;u.ascent?h=u.ascent*h:u.descent&&(h=(1+u.descent)*h);var f,m;if(0===c?(f=l[4],m=l[5]-h):(f=l[4]+h*Math.sin(c),m=l[5]-h*Math.cos(c)),p[1]=f,p[3]=m,p[5]=d,p[7]=u.fontFamily,o.style=p.join(""),r.setAttribute("style",o.style),r.textContent=i.str,s("pdfBug")&&(r.dataset.fontName=i.fontName),0!==c&&(o.angle=c*(180/Math.PI)),i.str.length>1&&(u.vertical?o.canvasWidth=i.height*t._viewport.scale:o.canvasWidth=i.width*t._viewport.scale),t._textDivProperties.set(r,o),t._enhanceTextSelection){var v=1,g=0;0!==c&&(v=Math.cos(c),g=Math.sin(c));var y,b,_=(u.vertical?i.height:i.width)*t._viewport.scale,x=d;0!==c?(y=[v,g,-g,v,f,m],b=n.getAxialAlignedBoundingBox([0,0,_,x],y)):b=[f,m,f+_,m+x],t._bounds.push({left:b[0],top:b[1],right:b[2],bottom:b[3],div:r,size:[_,x],m:y})}}function i(e){if(!e._canceled){var t=e._container,i=e._textDivs,n=e._capability,a=i.length;if(a>h)return e._renderingDone=!0,void n.resolve();var s=document.createElement("canvas");s.mozOpaque=!0;for(var o,l,c=s.getContext("2d",{alpha:!1}),u=0;u<a;u++){var d=i[u],f=e._textDivProperties.get(d);if(!f.isWhitespace){var p=d.style.fontSize,m=d.style.fontFamily;p===o&&m===l||(c.font=p+" "+m,o=p,l=m);var v=c.measureText(d.textContent).width;t.appendChild(d);var g="";0!==f.canvasWidth&&v>0&&(f.scale=f.canvasWidth/v,g="scaleX("+f.scale+")"),0!==f.angle&&(g="rotate("+f.angle+"deg) "+g),""!==g&&(f.originalTransform=g,r.setProp("transform",d,g)),e._textDivProperties.set(d,f)}}e._renderingDone=!0,n.resolve()}}function o(e){for(var t=e._bounds,i=e._viewport,a=l(i.width,i.height,t),r=0;r<a.length;r++){var s=t[r].div,o=e._textDivProperties.get(s);if(0!==o.angle){var c=a[r],u=t[r],d=u.m,h=d[0],f=d[1],p=[[0,0],[0,u.size[1]],[u.size[0],0],u.size],m=new Float64Array(64);p.forEach(function(e,t){var i=n.applyTransform(e,d);m[t+0]=h&&(c.left-i[0])/h,m[t+4]=f&&(c.top-i[1])/f,m[t+8]=h&&(c.right-i[0])/h,m[t+12]=f&&(c.bottom-i[1])/f,m[t+16]=f&&(c.left-i[0])/-f,m[t+20]=h&&(c.top-i[1])/h,m[t+24]=f&&(c.right-i[0])/-f,m[t+28]=h&&(c.bottom-i[1])/h,m[t+32]=h&&(c.left-i[0])/-h,m[t+36]=f&&(c.top-i[1])/-f,m[t+40]=h&&(c.right-i[0])/-h,m[t+44]=f&&(c.bottom-i[1])/-f,m[t+48]=f&&(c.left-i[0])/f,m[t+52]=h&&(c.top-i[1])/-h,m[t+56]=f&&(c.right-i[0])/f,m[t+60]=h&&(c.bottom-i[1])/-h});var v=function(e,t,i){for(var n=0,a=0;a<i;a++){var r=e[t++];r>0&&(n=n?Math.min(r,n):r)}return n},g=1+Math.min(Math.abs(h),Math.abs(f));o.paddingLeft=v(m,32,16)/g,o.paddingTop=v(m,48,16)/g,o.paddingRight=v(m,0,16)/g,o.paddingBottom=v(m,16,16)/g,e._textDivProperties.set(s,o)}else o.paddingLeft=t[r].left-a[r].left,o.paddingTop=t[r].top-a[r].top,o.paddingRight=a[r].right-t[r].right,o.paddingBottom=a[r].bottom-t[r].bottom,e._textDivProperties.set(s,o)}}function l(e,t,i){var n=i.map(function(e,t){return{x1:e.left,y1:e.top,x2:e.right,y2:e.bottom,index:t,x1New:void 0,x2New:void 0}});c(e,n);var a=new Array(i.length);return n.forEach(function(e){var t=e.index;a[t]={left:e.x1New,top:0,right:e.x2New,bottom:0}}),i.map(function(t,i){var r=a[i],s=n[i];s.x1=t.top,s.y1=e-r.right,s.x2=t.bottom,s.y2=e-r.left,s.index=i,s.x1New=void 0,s.x2New=void 0}),c(t,n),n.forEach(function(e){var t=e.index;a[t].top=e.x1New,a[t].bottom=e.x2New}),a}function c(e,t){t.sort(function(e,t){return e.x1-t.x1||e.index-t.index});var i={x1:-(1/0),y1:-(1/0),x2:0,y2:1/0,index:-1,x1New:0,x2New:0},n=[{start:-(1/0),end:1/0,boundary:i}];t.forEach(function(e){for(var t=0;t<n.length&&n[t].end<=e.y1;)t++;for(var i=n.length-1;i>=0&&n[i].start>=e.y2;)i--;var a,r,s,o,l=-(1/0);for(s=t;s<=i;s++){a=n[s],r=a.boundary;var c;c=r.x2>e.x1?r.index>e.index?r.x1New:e.x1:void 0===r.x2New?(r.x2+e.x1)/2:r.x2New,c>l&&(l=c)}for(e.x1New=l,s=t;s<=i;s++)a=n[s],r=a.boundary,void 0===r.x2New?r.x2>e.x1?r.index>e.index&&(r.x2New=r.x2):r.x2New=l:r.x2New>l&&(r.x2New=Math.max(l,r.x2));var u=[],d=null;for(s=t;s<=i;s++){a=n[s],r=a.boundary;var h=r.x2>e.x2?r:e;d===h?u[u.length-1].end=a.end:(u.push({start:a.start,end:a.end,boundary:h}),d=h)}for(n[t].start<e.y1&&(u[0].start=e.y1,u.unshift({start:n[t].start,end:e.y1,boundary:n[t].boundary})),e.y2<n[i].end&&(u[u.length-1].end=e.y2,u.push({start:e.y2,end:n[i].end,boundary:n[i].boundary})),s=t;s<=i;s++)if(a=n[s],r=a.boundary,void 0===r.x2New){var f=!1;for(o=t-1;!f&&o>=0&&n[o].start>=r.y1;o--)f=n[o].boundary===r;for(o=i+1;!f&&o<n.length&&n[o].end<=r.y2;o++)f=n[o].boundary===r;for(o=0;!f&&o<u.length;o++)f=u[o].boundary===r;f||(r.x2New=l)}Array.prototype.splice.apply(n,[t,i-t+1].concat(u))}),n.forEach(function(t){var i=t.boundary;void 0===i.x2New&&(i.x2New=Math.max(e,i.x2))})}function u(e,t,i,n,r){this._textContent=e,this._container=t,this._viewport=i,this._textDivs=n||[],this._textDivProperties=new WeakMap,this._renderingDone=!1,this._canceled=!1,this._capability=a(),this._renderTimer=null,this._bounds=[],this._enhanceTextSelection=!!r}function d(e){var t=new u(e.textContent,e.container,e.viewport,e.textDivs,e.enhanceTextSelection);return t._render(e.timeout),t}var h=1e5,f=/\S/,p=["left: ",0,"px; top: ",0,"px; font-size: ",0,"px; font-family: ","",";"];return u.prototype={get promise(){return this._capability.promise},cancel:function(){this._canceled=!0,null!==this._renderTimer&&(clearTimeout(this._renderTimer),this._renderTimer=null),this._capability.reject("canceled")},_render:function(e){for(var n=this._textContent.items,a=this._textContent.styles,r=0,s=n.length;r<s;r++)t(this,n[r],a);if(e){var o=this;this._renderTimer=setTimeout(function(){i(o),o._renderTimer=null},e)}else i(this)},expandTextDivs:function(e){if(this._enhanceTextSelection&&this._renderingDone){null!==this._bounds&&(o(this),this._bounds=null);for(var t=0,i=this._textDivs.length;t<i;t++){var n=this._textDivs[t],a=this._textDivProperties.get(n);if(!a.isWhitespace)if(e){var s="",l="";1!==a.scale&&(s="scaleX("+a.scale+")"),0!==a.angle&&(s="rotate("+a.angle+"deg) "+s),0!==a.paddingLeft&&(l+=" padding-left: "+a.paddingLeft/a.scale+"px;",s+=" translateX("+-a.paddingLeft/a.scale+"px)"),0!==a.paddingTop&&(l+=" padding-top: "+a.paddingTop+"px;",s+=" translateY("+-a.paddingTop+"px)"),0!==a.paddingRight&&(l+=" padding-right: "+a.paddingRight/a.scale+"px;"),0!==a.paddingBottom&&(l+=" padding-bottom: "+a.paddingBottom+"px;"),""!==l&&n.setAttribute("style",a.style+l),""!==s&&r.setProp("transform",n,s)}else n.style.padding=0,r.setProp("transform",n,a.originalTransform||"")}}}},d}();e.renderTextLayer=o}),function(e,t){t(e.pdfjsDisplayWebGL={},e.pdfjsSharedUtil,e.pdfjsDisplayDOMUtils)}(this,function(e,t,i){var n=t.shadow,a=i.getDefaultSetting,r=function(){function e(e,t,i){var n=e.createShader(i);e.shaderSource(n,t),e.compileShader(n);var a=e.getShaderParameter(n,e.COMPILE_STATUS);if(!a){var r=e.getShaderInfoLog(n);throw new Error("Error during shader compilation: "+r)}return n}function t(t,i){return e(t,i,t.VERTEX_SHADER)}function i(t,i){return e(t,i,t.FRAGMENT_SHADER)}function r(e,t){for(var i=e.createProgram(),n=0,a=t.length;n<a;++n)e.attachShader(i,t[n]);e.linkProgram(i);var r=e.getProgramParameter(i,e.LINK_STATUS);if(!r){var s=e.getProgramInfoLog(i);throw new Error("Error during program linking: "+s)}return i}function s(e,t,i){e.activeTexture(i);var n=e.createTexture();return e.bindTexture(e.TEXTURE_2D,n),e.texParameteri(e.TEXTURE_2D,e.TEXTURE_WRAP_S,e.CLAMP_TO_EDGE),e.texParameteri(e.TEXTURE_2D,e.TEXTURE_WRAP_T,e.CLAMP_TO_EDGE),e.texParameteri(e.TEXTURE_2D,e.TEXTURE_MIN_FILTER,e.NEAREST),e.texParameteri(e.TEXTURE_2D,e.TEXTURE_MAG_FILTER,e.NEAREST),e.texImage2D(e.TEXTURE_2D,0,e.RGBA,e.RGBA,e.UNSIGNED_BYTE,t),n}function o(){f||(p=document.createElement("canvas"),f=p.getContext("webgl",{premultipliedalpha:!1}))}function l(){var e,n;o(),e=p,p=null,n=f,f=null;var a=t(n,m),s=i(n,v),l=r(n,[a,s]);n.useProgram(l);var c={};c.gl=n,c.canvas=e,c.resolutionLocation=n.getUniformLocation(l,"u_resolution"),c.positionLocation=n.getAttribLocation(l,"a_position"),c.backdropLocation=n.getUniformLocation(l,"u_backdrop"),c.subtypeLocation=n.getUniformLocation(l,"u_subtype");var u=n.getAttribLocation(l,"a_texCoord"),d=n.getUniformLocation(l,"u_image"),h=n.getUniformLocation(l,"u_mask"),y=n.createBuffer();n.bindBuffer(n.ARRAY_BUFFER,y),n.bufferData(n.ARRAY_BUFFER,new Float32Array([0,0,1,0,0,1,0,1,1,0,1,1]),n.STATIC_DRAW),n.enableVertexAttribArray(u),n.vertexAttribPointer(u,2,n.FLOAT,!1,0,0),n.uniform1i(d,0),n.uniform1i(h,1),g=c}function c(e,t,i){var n=e.width,a=e.height;g||l();var r=g,o=r.canvas,c=r.gl;o.width=n,o.height=a,c.viewport(0,0,c.drawingBufferWidth,c.drawingBufferHeight),c.uniform2f(r.resolutionLocation,n,a),i.backdrop?c.uniform4f(r.resolutionLocation,i.backdrop[0],i.backdrop[1],i.backdrop[2],1):c.uniform4f(r.resolutionLocation,0,0,0,0),c.uniform1i(r.subtypeLocation,"Luminosity"===i.subtype?1:0);var u=s(c,e,c.TEXTURE0),d=s(c,t,c.TEXTURE1),h=c.createBuffer();return c.bindBuffer(c.ARRAY_BUFFER,h),c.bufferData(c.ARRAY_BUFFER,new Float32Array([0,0,n,0,0,a,0,a,n,0,n,a]),c.STATIC_DRAW),c.enableVertexAttribArray(r.positionLocation),c.vertexAttribPointer(r.positionLocation,2,c.FLOAT,!1,0,0),c.clearColor(0,0,0,0),c.enable(c.BLEND),c.blendFunc(c.ONE,c.ONE_MINUS_SRC_ALPHA),c.clear(c.COLOR_BUFFER_BIT),c.drawArrays(c.TRIANGLES,0,6),c.flush(),c.deleteTexture(u),c.deleteTexture(d),c.deleteBuffer(h),o}function u(){var e,n;o(),e=p,p=null,n=f,f=null;var a=t(n,y),s=i(n,b),l=r(n,[a,s]);n.useProgram(l);var c={};c.gl=n,c.canvas=e,c.resolutionLocation=n.getUniformLocation(l,"u_resolution"),c.scaleLocation=n.getUniformLocation(l,"u_scale"),c.offsetLocation=n.getUniformLocation(l,"u_offset"),c.positionLocation=n.getAttribLocation(l,"a_position"),c.colorLocation=n.getAttribLocation(l,"a_color"),_=c}function d(e,t,i,n,a){_||u();var r=_,s=r.canvas,o=r.gl;s.width=e,s.height=t,o.viewport(0,0,o.drawingBufferWidth,o.drawingBufferHeight),o.uniform2f(r.resolutionLocation,e,t);var l,c,d,h=0;for(l=0,c=n.length;l<c;l++)switch(n[l].type){case"lattice":d=n[l].coords.length/n[l].verticesPerRow|0,h+=(d-1)*(n[l].verticesPerRow-1)*6;break;case"triangles":h+=n[l].coords.length}var f=new Float32Array(2*h),p=new Uint8Array(3*h),m=a.coords,v=a.colors,g=0,y=0;for(l=0,c=n.length;l<c;l++){var b=n[l],x=b.coords,C=b.colors;switch(b.type){case"lattice":var w=b.verticesPerRow;d=x.length/w|0;for(var S=1;S<d;S++)for(var M=S*w+1,k=1;k<w;k++,M++)f[g]=m[x[M-w-1]],f[g+1]=m[x[M-w-1]+1],f[g+2]=m[x[M-w]],f[g+3]=m[x[M-w]+1],f[g+4]=m[x[M-1]],f[g+5]=m[x[M-1]+1],p[y]=v[C[M-w-1]],p[y+1]=v[C[M-w-1]+1],p[y+2]=v[C[M-w-1]+2],p[y+3]=v[C[M-w]],p[y+4]=v[C[M-w]+1],p[y+5]=v[C[M-w]+2],p[y+6]=v[C[M-1]],p[y+7]=v[C[M-1]+1],p[y+8]=v[C[M-1]+2],f[g+6]=f[g+2],f[g+7]=f[g+3],f[g+8]=f[g+4],f[g+9]=f[g+5],f[g+10]=m[x[M]],f[g+11]=m[x[M]+1],p[y+9]=p[y+3],p[y+10]=p[y+4],p[y+11]=p[y+5],p[y+12]=p[y+6],p[y+13]=p[y+7],p[y+14]=p[y+8],p[y+15]=v[C[M]],p[y+16]=v[C[M]+1],p[y+17]=v[C[M]+2],g+=12,y+=18;break;case"triangles":for(var A=0,T=x.length;A<T;A++)f[g]=m[x[A]],f[g+1]=m[x[A]+1],p[y]=v[C[A]],p[y+1]=v[C[A]+1],p[y+2]=v[C[A]+2],g+=2,y+=3}}i?o.clearColor(i[0]/255,i[1]/255,i[2]/255,1):o.clearColor(0,0,0,0),o.clear(o.COLOR_BUFFER_BIT);var E=o.createBuffer();o.bindBuffer(o.ARRAY_BUFFER,E),o.bufferData(o.ARRAY_BUFFER,f,o.STATIC_DRAW),o.enableVertexAttribArray(r.positionLocation),o.vertexAttribPointer(r.positionLocation,2,o.FLOAT,!1,0,0);var D=o.createBuffer();return o.bindBuffer(o.ARRAY_BUFFER,D),o.bufferData(o.ARRAY_BUFFER,p,o.STATIC_DRAW),o.enableVertexAttribArray(r.colorLocation),o.vertexAttribPointer(r.colorLocation,3,o.UNSIGNED_BYTE,!1,0,0),o.uniform2f(r.scaleLocation,a.scaleX,a.scaleY),o.uniform2f(r.offsetLocation,a.offsetX,a.offsetY), o.drawArrays(o.TRIANGLES,0,h),o.flush(),o.deleteBuffer(E),o.deleteBuffer(D),s}function h(){g&&g.canvas&&(g.canvas.width=0,g.canvas.height=0),_&&_.canvas&&(_.canvas.width=0,_.canvas.height=0),g=null,_=null}var f,p,m="\t attribute vec2 a_position; \t attribute vec2 a_texCoord; \t \t uniform vec2 u_resolution; \t \t varying vec2 v_texCoord; \t \t void main() { \t vec2 clipSpace = (a_position / u_resolution) * 2.0 - 1.0; \t gl_Position = vec4(clipSpace * vec2(1, -1), 0, 1); \t \t v_texCoord = a_texCoord; \t } ",v="\t precision mediump float; \t \t uniform vec4 u_backdrop; \t uniform int u_subtype; \t uniform sampler2D u_image; \t uniform sampler2D u_mask; \t \t varying vec2 v_texCoord; \t \t void main() { \t vec4 imageColor = texture2D(u_image, v_texCoord); \t vec4 maskColor = texture2D(u_mask, v_texCoord); \t if (u_backdrop.a > 0.0) { \t maskColor.rgb = maskColor.rgb * maskColor.a + \t u_backdrop.rgb * (1.0 - maskColor.a); \t } \t float lum; \t if (u_subtype == 0) { \t lum = maskColor.a; \t } else { \t lum = maskColor.r * 0.3 + maskColor.g * 0.59 + \t maskColor.b * 0.11; \t } \t imageColor.a *= lum; \t imageColor.rgb *= imageColor.a; \t gl_FragColor = imageColor; \t } ",g=null,y="\t attribute vec2 a_position; \t attribute vec3 a_color; \t \t uniform vec2 u_resolution; \t uniform vec2 u_scale; \t uniform vec2 u_offset; \t \t varying vec4 v_color; \t \t void main() { \t vec2 position = (a_position + u_offset) * u_scale; \t vec2 clipSpace = (position / u_resolution) * 2.0 - 1.0; \t gl_Position = vec4(clipSpace * vec2(1, -1), 0, 1); \t \t v_color = vec4(a_color / 255.0, 1.0); \t } ",b="\t precision mediump float; \t \t varying vec4 v_color; \t \t void main() { \t gl_FragColor = v_color; \t } ",_=null;return{get isEnabled(){if(a("disableWebGL"))return!1;var e=!1;try{o(),e=!!f}catch(e){}return n(this,"isEnabled",e)},composeSMask:c,drawFigures:d,clear:h}}();e.WebGLUtils=r}),function(e,t){t(e.pdfjsDisplayPatternHelper={},e.pdfjsSharedUtil,e.pdfjsDisplayWebGL)}(this,function(e,t,i){function n(e){var t=c[e[0]];return t||o("Unknown IR type: "+e[0]),t.fromIR(e)}var a=t.Util,r=t.info,s=t.isArray,o=t.error,l=i.WebGLUtils,c={};c.RadialAxial={fromIR:function(e){var t=e[1],i=e[2],n=e[3],a=e[4],r=e[5],s=e[6];return{type:"Pattern",getPattern:function(e){var o;"axial"===t?o=e.createLinearGradient(n[0],n[1],a[0],a[1]):"radial"===t&&(o=e.createRadialGradient(n[0],n[1],r,a[0],a[1],s));for(var l=0,c=i.length;l<c;++l){var u=i[l];o.addColorStop(u[0],u[1])}return o}}}};var u=function(){function e(e,t,i,n,a,r,s,o){var l,c=t.coords,u=t.colors,d=e.data,h=4*e.width;c[i+1]>c[n+1]&&(l=i,i=n,n=l,l=r,r=s,s=l),c[n+1]>c[a+1]&&(l=n,n=a,a=l,l=s,s=o,o=l),c[i+1]>c[n+1]&&(l=i,i=n,n=l,l=r,r=s,s=l);var f=(c[i]+t.offsetX)*t.scaleX,p=(c[i+1]+t.offsetY)*t.scaleY,m=(c[n]+t.offsetX)*t.scaleX,v=(c[n+1]+t.offsetY)*t.scaleY,g=(c[a]+t.offsetX)*t.scaleX,y=(c[a+1]+t.offsetY)*t.scaleY;if(!(p>=y))for(var b,_,x,C,w,S,M,k,A,T=u[r],E=u[r+1],D=u[r+2],I=u[s],P=u[s+1],N=u[s+2],O=u[o],F=u[o+1],L=u[o+2],j=Math.round(p),R=Math.round(y),$=j;$<=R;$++){$<v?(A=$<p?0:p===v?1:(p-$)/(p-v),b=f-(f-m)*A,_=T-(T-I)*A,x=E-(E-P)*A,C=D-(D-N)*A):(A=$>y?1:v===y?0:(v-$)/(v-y),b=m-(m-g)*A,_=I-(I-O)*A,x=P-(P-F)*A,C=N-(N-L)*A),A=$<p?0:$>y?1:(p-$)/(p-y),w=f-(f-g)*A,S=T-(T-O)*A,M=E-(E-F)*A,k=D-(D-L)*A;for(var B=Math.round(Math.min(b,w)),H=Math.round(Math.max(b,w)),z=h*$+4*B,W=B;W<=H;W++)A=(b-W)/(b-w),A=A<0?0:A>1?1:A,d[z++]=_-(_-S)*A|0,d[z++]=x-(x-M)*A|0,d[z++]=C-(C-k)*A|0,d[z++]=255}}function t(t,i,n){var a,r,s=i.coords,l=i.colors;switch(i.type){case"lattice":var c=i.verticesPerRow,u=Math.floor(s.length/c)-1,d=c-1;for(a=0;a<u;a++)for(var h=a*c,f=0;f<d;f++,h++)e(t,n,s[h],s[h+1],s[h+c],l[h],l[h+1],l[h+c]),e(t,n,s[h+c+1],s[h+1],s[h+c],l[h+c+1],l[h+1],l[h+c]);break;case"triangles":for(a=0,r=s.length;a<r;a+=3)e(t,n,s[a],s[a+1],s[a+2],l[a],l[a+1],l[a+2]);break;default:o("illigal figure")}}function i(e,i,n,a,r,s,o){var c,u,d,h,f=1.1,p=3e3,m=2,v=Math.floor(e[0]),g=Math.floor(e[1]),y=Math.ceil(e[2])-v,b=Math.ceil(e[3])-g,_=Math.min(Math.ceil(Math.abs(y*i[0]*f)),p),x=Math.min(Math.ceil(Math.abs(b*i[1]*f)),p),C=y/_,w=b/x,S={coords:n,colors:a,offsetX:-v,offsetY:-g,scaleX:1/C,scaleY:1/w},M=_+2*m,k=x+2*m;if(l.isEnabled)c=l.drawFigures(_,x,s,r,S),u=o.getCanvas("mesh",M,k,!1),u.context.drawImage(c,m,m),c=u.canvas;else{u=o.getCanvas("mesh",M,k,!1);var A=u.context,T=A.createImageData(_,x);if(s){var E=T.data;for(d=0,h=E.length;d<h;d+=4)E[d]=s[0],E[d+1]=s[1],E[d+2]=s[2],E[d+3]=255}for(d=0;d<r.length;d++)t(T,r[d],S);A.putImageData(T,m,m),c=u.canvas}return{canvas:c,offsetX:v-m*C,offsetY:g-m*w,scaleX:C,scaleY:w}}return i}();c.Mesh={fromIR:function(e){var t=e[2],i=e[3],n=e[4],r=e[5],s=e[6],o=e[8];return{type:"Pattern",getPattern:function(e,l,c){var d;if(c)d=a.singularValueDecompose2dScale(e.mozCurrentTransform);else if(d=a.singularValueDecompose2dScale(l.baseTransform),s){var h=a.singularValueDecompose2dScale(s);d=[d[0]*h[0],d[1]*h[1]]}var f=u(r,d,t,i,n,c?null:o,l.cachedCanvases);return c||(e.setTransform.apply(e,l.baseTransform),s&&e.transform.apply(e,s)),e.translate(f.offsetX,f.offsetY),e.scale(f.scaleX,f.scaleY),e.createPattern(f.canvas,"no-repeat")}}}},c.Dummy={fromIR:function(){return{type:"Pattern",getPattern:function(){return"hotpink"}}}};var d=function(){function e(e,t,i,n,a){this.operatorList=e[2],this.matrix=e[3]||[1,0,0,1,0,0],this.bbox=e[4],this.xstep=e[5],this.ystep=e[6],this.paintType=e[7],this.tilingType=e[8],this.color=t,this.canvasGraphicsFactory=n,this.baseTransform=a,this.type="Pattern",this.ctx=i}var t={COLORED:1,UNCOLORED:2},i=3e3;return e.prototype={createPatternCanvas:function(e){var t=this.operatorList,n=this.bbox,s=this.xstep,o=this.ystep,l=this.paintType,c=this.tilingType,u=this.color,d=this.canvasGraphicsFactory;r("TilingType: "+c);var h=n[0],f=n[1],p=n[2],m=n[3],v=[h,f],g=[h+s,f+o],y=g[0]-v[0],b=g[1]-v[1],_=a.singularValueDecompose2dScale(this.matrix),x=a.singularValueDecompose2dScale(this.baseTransform),C=[_[0]*x[0],_[1]*x[1]];y=Math.min(Math.ceil(Math.abs(y*C[0])),i),b=Math.min(Math.ceil(Math.abs(b*C[1])),i);var w=e.cachedCanvases.getCanvas("pattern",y,b,!0),S=w.context,M=d.createCanvasGraphics(S);M.groupLevel=e.groupLevel,this.setFillAndStrokeStyleToContext(S,l,u),this.setScale(y,b,s,o),this.transformToScale(M);var k=[1,0,0,1,-v[0],-v[1]];return M.transform.apply(M,k),this.clipBbox(M,n,h,f,p,m),M.executeOperatorList(t),w.canvas},setScale:function(e,t,i,n){this.scale=[e/i,t/n]},transformToScale:function(e){var t=this.scale,i=[t[0],0,0,t[1],0,0];e.transform.apply(e,i)},scaleToContext:function(){var e=this.scale;this.ctx.scale(1/e[0],1/e[1])},clipBbox:function(e,t,i,n,a,r){if(t&&s(t)&&4===t.length){var o=a-i,l=r-n;e.ctx.rect(i,n,o,l),e.clip(),e.endPath()}},setFillAndStrokeStyleToContext:function(e,i,n){switch(i){case t.COLORED:var r=this.ctx;e.fillStyle=r.fillStyle,e.strokeStyle=r.strokeStyle;break;case t.UNCOLORED:var s=a.makeCssRgb(n[0],n[1],n[2]);e.fillStyle=s,e.strokeStyle=s;break;default:o("Unsupported paint type: "+i)}},getPattern:function(e,t){var i=this.createPatternCanvas(t);return e=this.ctx,e.setTransform.apply(e,this.baseTransform),e.transform.apply(e,this.matrix),this.scaleToContext(),e.createPattern(i,"repeat")}},e}();e.getShadingPatternFromIR=n,e.TilingPattern=d}),function(e,t){t(e.pdfjsDisplayCanvas={},e.pdfjsSharedUtil,e.pdfjsDisplayDOMUtils,e.pdfjsDisplayPatternHelper,e.pdfjsDisplayWebGL)}(this,function(e,t,i,n,a){function r(e,t){var i=document.createElement("canvas");return i.width=e,i.height=t,i}function s(e){e.mozCurrentTransform||(e._originalSave=e.save,e._originalRestore=e.restore,e._originalRotate=e.rotate,e._originalScale=e.scale,e._originalTranslate=e.translate,e._originalTransform=e.transform,e._originalSetTransform=e.setTransform,e._transformMatrix=e._transformMatrix||[1,0,0,1,0,0],e._transformStack=[],Object.defineProperty(e,"mozCurrentTransform",{get:function(){return this._transformMatrix}}),Object.defineProperty(e,"mozCurrentTransformInverse",{get:function(){var e=this._transformMatrix,t=e[0],i=e[1],n=e[2],a=e[3],r=e[4],s=e[5],o=t*a-i*n,l=i*n-t*a;return[a/o,i/l,n/l,t/o,(a*r-n*s)/l,(i*r-t*s)/o]}}),e.save=function(){var e=this._transformMatrix;this._transformStack.push(e),this._transformMatrix=e.slice(0,6),this._originalSave()},e.restore=function(){var e=this._transformStack.pop();e&&(this._transformMatrix=e,this._originalRestore())},e.translate=function(e,t){var i=this._transformMatrix;i[4]=i[0]*e+i[2]*t+i[4],i[5]=i[1]*e+i[3]*t+i[5],this._originalTranslate(e,t)},e.scale=function(e,t){var i=this._transformMatrix;i[0]=i[0]*e,i[1]=i[1]*e,i[2]=i[2]*t,i[3]=i[3]*t,this._originalScale(e,t)},e.transform=function(t,i,n,a,r,s){var o=this._transformMatrix;this._transformMatrix=[o[0]*t+o[2]*i,o[1]*t+o[3]*i,o[0]*n+o[2]*a,o[1]*n+o[3]*a,o[0]*r+o[2]*s+o[4],o[1]*r+o[3]*s+o[5]],e._originalTransform(t,i,n,a,r,s)},e.setTransform=function(t,i,n,a,r,s){this._transformMatrix=[t,i,n,a,r,s],e._originalSetTransform(t,i,n,a,r,s)},e.rotate=function(e){var t=Math.cos(e),i=Math.sin(e),n=this._transformMatrix;this._transformMatrix=[n[0]*t+n[2]*i,n[1]*t+n[3]*i,n[0]*-i+n[2]*t,n[1]*-i+n[3]*t,n[4],n[5]],this._originalRotate(e)})}function o(e){var t,i,n,a,r=1e3,s=e.width,o=e.height,l=s+1,c=new Uint8Array(l*(o+1)),u=new Uint8Array([0,2,4,0,1,0,5,4,8,10,0,8,0,2,1,0]),d=s+7&-8,h=e.data,f=new Uint8Array(d*o),p=0;for(t=0,a=h.length;t<a;t++)for(var m=128,v=h[t];m>0;)f[p++]=v&m?0:255,m>>=1;var g=0;for(p=0,0!==f[p]&&(c[0]=1,++g),i=1;i<s;i++)f[p]!==f[p+1]&&(c[i]=f[p]?2:1,++g),p++;for(0!==f[p]&&(c[i]=2,++g),t=1;t<o;t++){p=t*d,n=t*l,f[p-d]!==f[p]&&(c[n]=f[p]?1:8,++g);var y=(f[p]?4:0)+(f[p-d]?8:0);for(i=1;i<s;i++)y=(y>>2)+(f[p+1]?4:0)+(f[p-d+1]?8:0),u[y]&&(c[n+i]=u[y],++g),p++;if(f[p-d]!==f[p]&&(c[n+i]=f[p]?2:4,++g),g>r)return null}for(p=d*(o-1),n=t*l,0!==f[p]&&(c[n]=8,++g),i=1;i<s;i++)f[p]!==f[p+1]&&(c[n+i]=f[p]?4:8,++g),p++;if(0!==f[p]&&(c[n+i]=4,++g),g>r)return null;var b=new Int32Array([0,l,-1,0,-l,0,0,0,1]),_=[];for(t=0;g&&t<=o;t++){for(var x=t*l,C=x+s;x<C&&!c[x];)x++;if(x!==C){var w,S=[x%l,t],M=c[x],k=x;do{var A=b[M];do x+=A;while(!c[x]);w=c[x],5!==w&&10!==w?(M=w,c[x]=0):(M=w&51*M>>4,c[x]&=M>>2|M<<2),S.push(x%l),S.push(x/l|0),--g}while(k!==x);_.push(S),--t}}var T=function(e){e.save(),e.scale(1/s,-1/o),e.translate(0,-o),e.beginPath();for(var t=0,i=_.length;t<i;t++){var n=_[t];e.moveTo(n[0],n[1]);for(var a=2,r=n.length;a<r;a+=2)e.lineTo(n[a],n[a+1])}e.fill(),e.beginPath(),e.restore()};return T}var l=t.FONT_IDENTITY_MATRIX,c=t.IDENTITY_MATRIX,u=t.ImageKind,d=t.OPS,h=t.TextRenderingMode,f=t.Uint32ArrayView,p=t.Util,m=t.assert,v=t.info,g=t.isNum,y=t.isArray,b=t.isLittleEndian,_=t.error,x=t.shadow,C=t.warn,w=n.TilingPattern,S=n.getShadingPatternFromIR,M=a.WebGLUtils,k=i.hasCanvasTypedArrays,A=16,T=100,E=4096,D=.65,I=!0,P=1e3,N=16,O={get value(){return x(O,"value",k())}},F={get value(){return x(F,"value",b())}},L=function(){function e(){this.cache=Object.create(null)}return e.prototype={getCanvas:function(e,t,i,n){var a;if(void 0!==this.cache[e])a=this.cache[e],a.canvas.width=t,a.canvas.height=i,a.context.setTransform(1,0,0,1,0,0);else{var o=r(t,i),l=o.getContext("2d");n&&s(l),this.cache[e]=a={canvas:o,context:l}}return a},clear:function(){for(var e in this.cache){var t=this.cache[e];t.canvas.width=0,t.canvas.height=0,delete this.cache[e]}}},e}(),j=function(){function e(e){this.alphaIsShape=!1,this.fontSize=0,this.fontSizeScale=1,this.textMatrix=c,this.textMatrixScale=1,this.fontMatrix=l,this.leading=0,this.x=0,this.y=0,this.lineX=0,this.lineY=0,this.charSpacing=0,this.wordSpacing=0,this.textHScale=1,this.textRenderingMode=h.FILL,this.textRise=0,this.fillColor="#000000",this.strokeColor="#000000",this.patternFill=!1,this.fillAlpha=1,this.strokeAlpha=1,this.lineWidth=1,this.activeSMask=null,this.resumeSMaskCtx=null,this.old=e}return e.prototype={clone:function(){return Object.create(this)},setCurrentPoint:function(e,t){this.x=e,this.y=t}},e}(),R=function(){function e(e,t,i,n){this.ctx=e,this.current=new j,this.stateStack=[],this.pendingClip=null,this.pendingEOFill=!1,this.res=null,this.xobjs=null,this.commonObjs=t,this.objs=i,this.imageLayer=n,this.groupStack=[],this.processingType3=null,this.baseTransform=null,this.baseTransformStack=[],this.groupLevel=0,this.smaskStack=[],this.smaskCounter=0,this.tempSMask=null,this.cachedCanvases=new L,e&&s(e),this.cachedGetSinglePixelWidth=null}function t(e,t){if("undefined"!=typeof ImageData&&t instanceof ImageData)return void e.putImageData(t,0,0);var i,n,a,r,s,o=t.height,l=t.width,c=o%N,d=(o-c)/N,h=0===c?d:d+1,p=e.createImageData(l,N),m=0,v=t.data,g=p.data;if(t.kind===u.GRAYSCALE_1BPP){var y=v.byteLength,b=O.value?new Uint32Array(g.buffer):new f(g),x=b.length,C=l+7>>3,w=4294967295,S=F.value||!O.value?4278190080:255;for(n=0;n<h;n++){for(r=n<d?N:c,i=0,a=0;a<r;a++){for(var M=y-m,k=0,A=M>C?l:8*M-7,T=A&-8,E=0,D=0;k<T;k+=8)D=v[m++],b[i++]=128&D?w:S,b[i++]=64&D?w:S,b[i++]=32&D?w:S,b[i++]=16&D?w:S,b[i++]=8&D?w:S,b[i++]=4&D?w:S,b[i++]=2&D?w:S,b[i++]=1&D?w:S;for(;k<A;k++)0===E&&(D=v[m++],E=128),b[i++]=D&E?w:S,E>>=1}for(;i<x;)b[i++]=0;e.putImageData(p,0,n*N)}}else if(t.kind===u.RGBA_32BPP){for(a=0,s=l*N*4,n=0;n<d;n++)g.set(v.subarray(m,m+s)),m+=s,e.putImageData(p,0,a),a+=N;n<h&&(s=l*c*4,g.set(v.subarray(m,m+s)),e.putImageData(p,0,a))}else if(t.kind===u.RGB_24BPP)for(r=N,s=l*r,n=0;n<h;n++){for(n>=d&&(r=c,s=l*r),i=0,a=s;a--;)g[i++]=v[m++],g[i++]=v[m++],g[i++]=v[m++],g[i++]=255;e.putImageData(p,0,n*N)}else _("bad image kind: "+t.kind)}function i(e,t){for(var i=t.height,n=t.width,a=i%N,r=(i-a)/N,s=0===a?r:r+1,o=e.createImageData(n,N),l=0,c=t.data,u=o.data,d=0;d<s;d++){for(var h=d<r?N:a,f=3,p=0;p<h;p++)for(var m=0,v=0;v<n;v++){if(!m){var g=c[l++];m=128}u[f]=g&m?0:255,f+=4,m>>=1}e.putImageData(o,0,d*N)}}function n(e,t){for(var i=["strokeStyle","fillStyle","fillRule","globalAlpha","lineWidth","lineCap","lineJoin","miterLimit","globalCompositeOperation","font"],n=0,a=i.length;n<a;n++){var r=i[n];void 0!==e[r]&&(t[r]=e[r])}void 0!==e.setLineDash&&(t.setLineDash(e.getLineDash()),t.lineDashOffset=e.lineDashOffset)}function a(e,t,i,n){for(var a=e.length,r=3;r<a;r+=4){var s=e[r];if(0===s)e[r-3]=t,e[r-2]=i,e[r-1]=n;else if(s<255){var o=255-s;e[r-3]=e[r-3]*s+t*o>>8,e[r-2]=e[r-2]*s+i*o>>8,e[r-1]=e[r-1]*s+n*o>>8}}}function r(e,t,i){for(var n=e.length,a=1/255,r=3;r<n;r+=4){var s=i?i[e[r]]:e[r];t[r]=t[r]*s*a|0}}function b(e,t,i){for(var n=e.length,a=3;a<n;a+=4){var r=77*e[a-3]+152*e[a-2]+28*e[a-1];t[a]=i?t[a]*i[r>>8]>>8:t[a]*r>>16}}function k(e,t,i,n,s,o,l){var c,u=!!o,d=u?o[0]:0,h=u?o[1]:0,f=u?o[2]:0;c="Luminosity"===s?b:r;for(var p=1048576,m=Math.min(n,Math.ceil(p/i)),v=0;v<n;v+=m){var g=Math.min(m,n-v),y=e.getImageData(0,v,i,g),_=t.getImageData(0,v,i,g);u&&a(y.data,d,h,f),c(y.data,_.data,l),e.putImageData(_,0,v)}}function R(e,t,i){var n=t.canvas,a=t.context;e.setTransform(t.scaleX,0,0,t.scaleY,t.offsetX,t.offsetY);var r=t.backdrop||null;if(!t.transferMap&&M.isEnabled){var s=M.composeSMask(i.canvas,n,{subtype:t.subtype,backdrop:r});return e.setTransform(1,0,0,1,0,0),void e.drawImage(s,t.offsetX,t.offsetY)}k(a,i,n.width,n.height,t.subtype,r,t.transferMap),e.drawImage(n,0,0)}var $=15,B=10,H=["butt","round","square"],z=["miter","round","bevel"],W={},V={};e.prototype={beginDrawing:function(e,t,i){var n=this.ctx.canvas.width,a=this.ctx.canvas.height;if(this.ctx.save(),this.ctx.fillStyle="rgb(255, 255, 255)",this.ctx.fillRect(0,0,n,a),this.ctx.restore(),i){var r=this.cachedCanvases.getCanvas("transparent",n,a,!0);this.compositeCtx=this.ctx,this.transparentCanvas=r.canvas,this.ctx=r.context,this.ctx.save(),this.ctx.transform.apply(this.ctx,this.compositeCtx.mozCurrentTransform)}this.ctx.save(),e&&this.ctx.transform.apply(this.ctx,e),this.ctx.transform.apply(this.ctx,t.transform),this.baseTransform=this.ctx.mozCurrentTransform.slice(),this.imageLayer&&this.imageLayer.beginLayout()},executeOperatorList:function(e,t,i,n){var a=e.argsArray,r=e.fnArray,s=t||0,o=a.length;if(o===s)return s;for(var l,c=o-s>B&&"function"==typeof i,u=c?Date.now()+$:0,h=0,f=this.commonObjs,p=this.objs;;){if(void 0!==n&&s===n.nextBreakPoint)return n.breakIt(s,i),s;if(l=r[s],l!==d.dependency)this[l].apply(this,a[s]);else for(var m=a[s],v=0,g=m.length;v<g;v++){var y=m[v],b="g"===y[0]&&"_"===y[1],_=b?f:p;if(!_.isResolved(y))return _.get(y,i),s}if(s++,s===o)return s;if(c&&++h>B){if(Date.now()>u)return i(),s;h=0}}},endDrawing:function(){null!==this.current.activeSMask&&this.endSMaskGroup(),this.ctx.restore(),this.transparentCanvas&&(this.ctx=this.compositeCtx,this.ctx.save(),this.ctx.setTransform(1,0,0,1,0,0),this.ctx.drawImage(this.transparentCanvas,0,0),this.ctx.restore(),this.transparentCanvas=null),this.cachedCanvases.clear(),M.clear(),this.imageLayer&&this.imageLayer.endLayout()},setLineWidth:function(e){this.current.lineWidth=e,this.ctx.lineWidth=e},setLineCap:function(e){this.ctx.lineCap=H[e]},setLineJoin:function(e){this.ctx.lineJoin=z[e]},setMiterLimit:function(e){this.ctx.miterLimit=e},setDash:function(e,t){var i=this.ctx;void 0!==i.setLineDash&&(i.setLineDash(e),i.lineDashOffset=t)},setRenderingIntent:function(e){},setFlatness:function(e){},setGState:function(e){for(var t=0,i=e.length;t<i;t++){var n=e[t],a=n[0],r=n[1];switch(a){case"LW":this.setLineWidth(r);break;case"LC":this.setLineCap(r);break;case"LJ":this.setLineJoin(r);break;case"ML":this.setMiterLimit(r);break;case"D":this.setDash(r[0],r[1]);break;case"RI":this.setRenderingIntent(r);break;case"FL":this.setFlatness(r);break;case"Font":this.setFont(r[0],r[1]);break;case"CA":this.current.strokeAlpha=n[1];break;case"ca":this.current.fillAlpha=n[1],this.ctx.globalAlpha=n[1];break;case"BM":if(r&&r.name&&"Normal"!==r.name){var s=r.name.replace(/([A-Z])/g,function(e){return"-"+e.toLowerCase()}).substring(1);this.ctx.globalCompositeOperation=s,this.ctx.globalCompositeOperation!==s&&C('globalCompositeOperation "'+s+'" is not supported')}else this.ctx.globalCompositeOperation="source-over";break;case"SMask":this.current.activeSMask&&(this.stateStack.length>0&&this.stateStack[this.stateStack.length-1].activeSMask===this.current.activeSMask?this.suspendSMaskGroup():this.endSMaskGroup()),this.current.activeSMask=r?this.tempSMask:null,this.current.activeSMask&&this.beginSMaskGroup(),this.tempSMask=null}}},beginSMaskGroup:function(){var e=this.current.activeSMask,t=e.canvas.width,i=e.canvas.height,a="smaskGroupAt"+this.groupLevel,r=this.cachedCanvases.getCanvas(a,t,i,!0),s=this.ctx,o=s.mozCurrentTransform;this.ctx.save();var l=r.context;l.scale(1/e.scaleX,1/e.scaleY),l.translate(-e.offsetX,-e.offsetY),l.transform.apply(l,o),e.startTransformInverse=l.mozCurrentTransformInverse,n(s,l),this.ctx=l,this.setGState([["BM","Normal"],["ca",1],["CA",1]]),this.groupStack.push(s),this.groupLevel++},suspendSMaskGroup:function(){var e=this.ctx;this.groupLevel--,this.ctx=this.groupStack.pop(),R(this.ctx,this.current.activeSMask,e),this.ctx.restore(),this.ctx.save(),n(e,this.ctx),this.current.resumeSMaskCtx=e;var t=p.transform(this.current.activeSMask.startTransformInverse,e.mozCurrentTransform);this.ctx.transform.apply(this.ctx,t),e.save(),e.setTransform(1,0,0,1,0,0),e.clearRect(0,0,e.canvas.width,e.canvas.height),e.restore()},resumeSMaskGroup:function(){var e=this.current.resumeSMaskCtx,t=this.ctx;this.ctx=e,this.groupStack.push(t),this.groupLevel++},endSMaskGroup:function(){var e=this.ctx;this.groupLevel--,this.ctx=this.groupStack.pop(),R(this.ctx,this.current.activeSMask,e),this.ctx.restore(),n(e,this.ctx);var t=p.transform(this.current.activeSMask.startTransformInverse,e.mozCurrentTransform);this.ctx.transform.apply(this.ctx,t)},save:function(){this.ctx.save();var e=this.current;this.stateStack.push(e),this.current=e.clone(),this.current.resumeSMaskCtx=null},restore:function(){this.current.resumeSMaskCtx&&this.resumeSMaskGroup(),null===this.current.activeSMask||0!==this.stateStack.length&&this.stateStack[this.stateStack.length-1].activeSMask===this.current.activeSMask||this.endSMaskGroup(),0!==this.stateStack.length&&(this.current=this.stateStack.pop(),this.ctx.restore(),this.pendingClip=null,this.cachedGetSinglePixelWidth=null)},transform:function(e,t,i,n,a,r){this.ctx.transform(e,t,i,n,a,r),this.cachedGetSinglePixelWidth=null},constructPath:function(e,t){for(var i=this.ctx,n=this.current,a=n.x,r=n.y,s=0,o=0,l=e.length;s<l;s++)switch(0|e[s]){case d.rectangle:a=t[o++],r=t[o++];var c=t[o++],u=t[o++];0===c&&(c=this.getSinglePixelWidth()),0===u&&(u=this.getSinglePixelWidth());var h=a+c,f=r+u;this.ctx.moveTo(a,r),this.ctx.lineTo(h,r),this.ctx.lineTo(h,f),this.ctx.lineTo(a,f),this.ctx.lineTo(a,r),this.ctx.closePath();break;case d.moveTo:a=t[o++],r=t[o++],i.moveTo(a,r);break;case d.lineTo:a=t[o++],r=t[o++],i.lineTo(a,r);break;case d.curveTo:a=t[o+4],r=t[o+5],i.bezierCurveTo(t[o],t[o+1],t[o+2],t[o+3],a,r),o+=6;break;case d.curveTo2:i.bezierCurveTo(a,r,t[o],t[o+1],t[o+2],t[o+3]),a=t[o+2],r=t[o+3],o+=4;break;case d.curveTo3:a=t[o+2],r=t[o+3],i.bezierCurveTo(t[o],t[o+1],a,r,a,r),o+=4;break;case d.closePath:i.closePath()}n.setCurrentPoint(a,r)},closePath:function(){this.ctx.closePath()},stroke:function(e){e="undefined"==typeof e||e;var t=this.ctx,i=this.current.strokeColor;t.lineWidth=Math.max(this.getSinglePixelWidth()*D,this.current.lineWidth),t.globalAlpha=this.current.strokeAlpha,i&&i.hasOwnProperty("type")&&"Pattern"===i.type?(t.save(),t.strokeStyle=i.getPattern(t,this),t.stroke(),t.restore()):t.stroke(),e&&this.consumePath(),t.globalAlpha=this.current.fillAlpha},closeStroke:function(){this.closePath(),this.stroke()},fill:function(e){e="undefined"==typeof e||e;var t=this.ctx,i=this.current.fillColor,n=this.current.patternFill,a=!1;n&&(t.save(),this.baseTransform&&t.setTransform.apply(t,this.baseTransform),t.fillStyle=i.getPattern(t,this),a=!0),this.pendingEOFill?(void 0!==t.mozFillRule?(t.mozFillRule="evenodd",t.fill(),t.mozFillRule="nonzero"):t.fill("evenodd"),this.pendingEOFill=!1):t.fill(),a&&t.restore(),e&&this.consumePath()},eoFill:function(){this.pendingEOFill=!0,this.fill()},fillStroke:function(){this.fill(!1),this.stroke(!1),this.consumePath()},eoFillStroke:function(){this.pendingEOFill=!0,this.fillStroke()},closeFillStroke:function(){this.closePath(),this.fillStroke()},closeEOFillStroke:function(){this.pendingEOFill=!0,this.closePath(),this.fillStroke()},endPath:function(){this.consumePath()},clip:function(){this.pendingClip=W},eoClip:function(){this.pendingClip=V},beginText:function(){this.current.textMatrix=c,this.current.textMatrixScale=1,this.current.x=this.current.lineX=0,this.current.y=this.current.lineY=0},endText:function(){var e=this.pendingTextPaths,t=this.ctx;if(void 0===e)return void t.beginPath();t.save(),t.beginPath();for(var i=0;i<e.length;i++){var n=e[i];t.setTransform.apply(t,n.transform),t.translate(n.x,n.y),n.addToPath(t,n.fontSize)}t.restore(),t.clip(),t.beginPath(),delete this.pendingTextPaths},setCharSpacing:function(e){this.current.charSpacing=e},setWordSpacing:function(e){this.current.wordSpacing=e},setHScale:function(e){this.current.textHScale=e/100},setLeading:function(e){this.current.leading=-e},setFont:function(e,t){var i=this.commonObjs.get(e),n=this.current;if(i||_("Can't find font for "+e),n.fontMatrix=i.fontMatrix?i.fontMatrix:l,0!==n.fontMatrix[0]&&0!==n.fontMatrix[3]||C("Invalid font matrix for font "+e),t<0?(t=-t,n.fontDirection=-1):n.fontDirection=1,this.current.font=i,this.current.fontSize=t,!i.isType3Font){var a=i.loadedName||"sans-serif",r=i.black?i.bold?"900":"bold":i.bold?"bold":"normal",s=i.italic?"italic":"normal",o='"'+a+'", '+i.fallbackName,c=t<A?A:t>T?T:t;this.current.fontSizeScale=t/c;var u=s+" "+r+" "+c+"px "+o;this.ctx.font=u}},setTextRenderingMode:function(e){this.current.textRenderingMode=e},setTextRise:function(e){this.current.textRise=e},moveText:function(e,t){this.current.x=this.current.lineX+=e,this.current.y=this.current.lineY+=t},setLeadingMoveText:function(e,t){this.setLeading(-t),this.moveText(e,t)},setTextMatrix:function(e,t,i,n,a,r){this.current.textMatrix=[e,t,i,n,a,r],this.current.textMatrixScale=Math.sqrt(e*e+t*t),this.current.x=this.current.lineX=0,this.current.y=this.current.lineY=0},nextLine:function(){this.moveText(0,this.current.leading)},paintChar:function(e,t,i){var n,a=this.ctx,r=this.current,s=r.font,o=r.textRenderingMode,l=r.fontSize/r.fontSizeScale,c=o&h.FILL_STROKE_MASK,u=!!(o&h.ADD_TO_PATH_FLAG);if((s.disableFontFace||u)&&(n=s.getPathGenerator(this.commonObjs,e)),s.disableFontFace?(a.save(),a.translate(t,i),a.beginPath(),n(a,l),c!==h.FILL&&c!==h.FILL_STROKE||a.fill(),c!==h.STROKE&&c!==h.FILL_STROKE||a.stroke(),a.restore()):(c!==h.FILL&&c!==h.FILL_STROKE||a.fillText(e,t,i),c!==h.STROKE&&c!==h.FILL_STROKE||a.strokeText(e,t,i)),u){var d=this.pendingTextPaths||(this.pendingTextPaths=[]);d.push({transform:a.mozCurrentTransform,x:t,y:i,fontSize:l,addToPath:n})}},get isFontSubpixelAAEnabled(){var e=document.createElement("canvas").getContext("2d");e.scale(1.5,1),e.fillText("I",0,10);for(var t=e.getImageData(0,0,10,10).data,i=!1,n=3;n<t.length;n+=4)if(t[n]>0&&t[n]<255){i=!0;break}return x(this,"isFontSubpixelAAEnabled",i)},showText:function(e){var t=this.current,i=t.font;if(i.isType3Font)return this.showType3Text(e);var n=t.fontSize;if(0!==n){var a=this.ctx,r=t.fontSizeScale,s=t.charSpacing,o=t.wordSpacing,l=t.fontDirection,c=t.textHScale*l,u=e.length,d=i.vertical,f=d?1:-1,p=i.defaultVMetrics,m=n*t.fontMatrix[0],v=t.textRenderingMode===h.FILL&&!i.disableFontFace;a.save(),a.transform.apply(a,t.textMatrix),a.translate(t.x,t.y+t.textRise),t.patternFill&&(a.fillStyle=t.fillColor.getPattern(a,this)),l>0?a.scale(c,-1):a.scale(c,1);var y=t.lineWidth,b=t.textMatrixScale;if(0===b||0===y){var _=t.textRenderingMode&h.FILL_STROKE_MASK;_!==h.STROKE&&_!==h.FILL_STROKE||(this.cachedGetSinglePixelWidth=null,y=this.getSinglePixelWidth()*D)}else y/=b;1!==r&&(a.scale(r,r),y/=r),a.lineWidth=y;var x,C=0;for(x=0;x<u;++x){var w=e[x];if(g(w))C+=f*w*n/1e3;else{var S,M,k,A,T=!1,E=(w.isSpace?o:0)+s,I=w.fontChar,P=w.accent,N=w.width;if(d){var O,F,L;O=w.vmetric||p,F=w.vmetric?O[1]:.5*N,F=-F*m,L=O[2]*m,N=O?-O[0]:N,S=F/r,M=(C+L)/r}else S=C/r,M=0;if(i.remeasure&&N>0){var j=1e3*a.measureText(I).width/n*r;if(N<j&&this.isFontSubpixelAAEnabled){var R=N/j;T=!0,a.save(),a.scale(R,1),S/=R}else N!==j&&(S+=(N-j)/2e3*n/r)}(w.isInFont||i.missingFile)&&(v&&!P?a.fillText(I,S,M):(this.paintChar(I,S,M),P&&(k=S+P.offset.x/r,A=M-P.offset.y/r,this.paintChar(P.fontChar,k,A))));var $=N*m+E*l;C+=$,T&&a.restore()}}d?t.y-=C*c:t.x+=C*c,a.restore()}},showType3Text:function(e){var t,i,n,a,r=this.ctx,s=this.current,o=s.font,c=s.fontSize,u=s.fontDirection,d=o.vertical?1:-1,f=s.charSpacing,m=s.wordSpacing,v=s.textHScale*u,y=s.fontMatrix||l,b=e.length,_=s.textRenderingMode===h.INVISIBLE;if(!_&&0!==c){for(this.cachedGetSinglePixelWidth=null,r.save(),r.transform.apply(r,s.textMatrix),r.translate(s.x,s.y),r.scale(v,u),t=0;t<b;++t)if(i=e[t],g(i))a=d*i*c/1e3,this.ctx.translate(a,0),s.x+=a*v;else{var x=(i.isSpace?m:0)+f,w=o.charProcOperatorList[i.operatorListId];if(w){this.processingType3=i,this.save(),r.scale(c,c),r.transform.apply(r,y),this.executeOperatorList(w),this.restore();var S=p.applyTransform([i.width,0],y);n=S[0]*c+x,r.translate(n,0),s.x+=n*v}else C('Type3 character "'+i.operatorListId+'" is not available')}r.restore(),this.processingType3=null}},setCharWidth:function(e,t){},setCharWidthAndBounds:function(e,t,i,n,a,r){this.ctx.rect(i,n,a-i,r-n),this.clip(),this.endPath()},getColorN_Pattern:function(t){var i;if("TilingPattern"===t[0]){var n=t[1],a=this.baseTransform||this.ctx.mozCurrentTransform.slice(),r=this,s={createCanvasGraphics:function(t){return new e(t,r.commonObjs,r.objs)}};i=new w(t,n,this.ctx,s,a)}else i=S(t);return i},setStrokeColorN:function(){this.current.strokeColor=this.getColorN_Pattern(arguments)},setFillColorN:function(){this.current.fillColor=this.getColorN_Pattern(arguments),this.current.patternFill=!0},setStrokeRGBColor:function(e,t,i){var n=p.makeCssRgb(e,t,i);this.ctx.strokeStyle=n,this.current.strokeColor=n},setFillRGBColor:function(e,t,i){var n=p.makeCssRgb(e,t,i);this.ctx.fillStyle=n,this.current.fillColor=n,this.current.patternFill=!1},shadingFill:function(e){var t=this.ctx;this.save();var i=S(e);t.fillStyle=i.getPattern(t,this,!0);var n=t.mozCurrentTransformInverse;if(n){var a=t.canvas,r=a.width,s=a.height,o=p.applyTransform([0,0],n),l=p.applyTransform([0,s],n),c=p.applyTransform([r,0],n),u=p.applyTransform([r,s],n),d=Math.min(o[0],l[0],c[0],u[0]),h=Math.min(o[1],l[1],c[1],u[1]),f=Math.max(o[0],l[0],c[0],u[0]),m=Math.max(o[1],l[1],c[1],u[1]);this.ctx.fillRect(d,h,f-d,m-h)}else this.ctx.fillRect(-1e10,-1e10,2e10,2e10);this.restore()},beginInlineImage:function(){_("Should not call beginInlineImage")},beginImageData:function(){_("Should not call beginImageData")},paintFormXObjectBegin:function(e,t){if(this.save(),this.baseTransformStack.push(this.baseTransform),y(e)&&6===e.length&&this.transform.apply(this,e),this.baseTransform=this.ctx.mozCurrentTransform,y(t)&&4===t.length){var i=t[2]-t[0],n=t[3]-t[1];this.ctx.rect(t[0],t[1],i,n),this.clip(),this.endPath()}},paintFormXObjectEnd:function(){this.restore(),this.baseTransform=this.baseTransformStack.pop()},beginGroup:function(e){this.save();var t=this.ctx;e.isolated||v("TODO: Support non-isolated groups."),e.knockout&&C("Knockout groups not supported.");var i=t.mozCurrentTransform;e.matrix&&t.transform.apply(t,e.matrix),m(e.bbox,"Bounding box is required."); var a=p.getAxialAlignedBoundingBox(e.bbox,t.mozCurrentTransform),r=[0,0,t.canvas.width,t.canvas.height];a=p.intersect(a,r)||[0,0,0,0];var s=Math.floor(a[0]),o=Math.floor(a[1]),l=Math.max(Math.ceil(a[2])-s,1),c=Math.max(Math.ceil(a[3])-o,1),u=1,d=1;l>E&&(u=l/E,l=E),c>E&&(d=c/E,c=E);var h="groupAt"+this.groupLevel;e.smask&&(h+="_smask_"+this.smaskCounter++%2);var f=this.cachedCanvases.getCanvas(h,l,c,!0),g=f.context;g.scale(1/u,1/d),g.translate(-s,-o),g.transform.apply(g,i),e.smask?this.smaskStack.push({canvas:f.canvas,context:g,offsetX:s,offsetY:o,scaleX:u,scaleY:d,subtype:e.smask.subtype,backdrop:e.smask.backdrop,transferMap:e.smask.transferMap||null,startTransformInverse:null}):(t.setTransform(1,0,0,1,0,0),t.translate(s,o),t.scale(u,d)),n(t,g),this.ctx=g,this.setGState([["BM","Normal"],["ca",1],["CA",1]]),this.groupStack.push(t),this.groupLevel++,this.current.activeSMask=null},endGroup:function(e){this.groupLevel--;var t=this.ctx;this.ctx=this.groupStack.pop(),void 0!==this.ctx.imageSmoothingEnabled?this.ctx.imageSmoothingEnabled=!1:this.ctx.mozImageSmoothingEnabled=!1,e.smask?this.tempSMask=this.smaskStack.pop():this.ctx.drawImage(t.canvas,0,0),this.restore()},beginAnnotations:function(){this.save(),this.current=new j,this.baseTransform&&this.ctx.setTransform.apply(this.ctx,this.baseTransform)},endAnnotations:function(){this.restore()},beginAnnotation:function(e,t,i){if(this.save(),y(e)&&4===e.length){var n=e[2]-e[0],a=e[3]-e[1];this.ctx.rect(e[0],e[1],n,a),this.clip(),this.endPath()}this.transform.apply(this,t),this.transform.apply(this,i)},endAnnotation:function(){this.restore()},paintJpegXObject:function(e,t,i){var n=this.objs.get(e);if(!n)return void C("Dependent image isn't ready yet");this.save();var a=this.ctx;if(a.scale(1/t,-1/i),a.drawImage(n,0,0,n.width,n.height,0,-i,t,i),this.imageLayer){var r=a.mozCurrentTransformInverse,s=this.getCanvasPosition(0,0);this.imageLayer.appendImage({objId:e,left:s[0],top:s[1],width:t/r[0],height:i/r[3]})}this.restore()},paintImageMaskXObject:function(e){var t=this.ctx,n=e.width,a=e.height,r=this.current.fillColor,s=this.current.patternFill,l=this.processingType3;if(I&&l&&void 0===l.compiled&&(n<=P&&a<=P?l.compiled=o({data:e.data,width:n,height:a}):l.compiled=null),l&&l.compiled)return void l.compiled(t);var c=this.cachedCanvases.getCanvas("maskCanvas",n,a),u=c.context;u.save(),i(u,e),u.globalCompositeOperation="source-in",u.fillStyle=s?r.getPattern(u,this):r,u.fillRect(0,0,n,a),u.restore(),this.paintInlineImageXObject(c.canvas)},paintImageMaskXObjectRepeat:function(e,t,n,a){var r=e.width,s=e.height,o=this.current.fillColor,l=this.current.patternFill,c=this.cachedCanvases.getCanvas("maskCanvas",r,s),u=c.context;u.save(),i(u,e),u.globalCompositeOperation="source-in",u.fillStyle=l?o.getPattern(u,this):o,u.fillRect(0,0,r,s),u.restore();for(var d=this.ctx,h=0,f=a.length;h<f;h+=2)d.save(),d.transform(t,0,0,n,a[h],a[h+1]),d.scale(1,-1),d.drawImage(c.canvas,0,0,r,s,0,-1,1,1),d.restore()},paintImageMaskXObjectGroup:function(e){for(var t=this.ctx,n=this.current.fillColor,a=this.current.patternFill,r=0,s=e.length;r<s;r++){var o=e[r],l=o.width,c=o.height,u=this.cachedCanvases.getCanvas("maskCanvas",l,c),d=u.context;d.save(),i(d,o),d.globalCompositeOperation="source-in",d.fillStyle=a?n.getPattern(d,this):n,d.fillRect(0,0,l,c),d.restore(),t.save(),t.transform.apply(t,o.transform),t.scale(1,-1),t.drawImage(u.canvas,0,0,l,c,0,-1,1,1),t.restore()}},paintImageXObject:function(e){var t=this.objs.get(e);return t?void this.paintInlineImageXObject(t):void C("Dependent image isn't ready yet")},paintImageXObjectRepeat:function(e,t,i,n){var a=this.objs.get(e);if(!a)return void C("Dependent image isn't ready yet");for(var r=a.width,s=a.height,o=[],l=0,c=n.length;l<c;l+=2)o.push({transform:[t,0,0,i,n[l],n[l+1]],x:0,y:0,w:r,h:s});this.paintInlineImageXObjectGroup(a,o)},paintInlineImageXObject:function(e){var i=e.width,n=e.height,a=this.ctx;this.save(),a.scale(1/i,-1/n);var r,s,o=a.mozCurrentTransformInverse,l=o[0],c=o[1],u=Math.max(Math.sqrt(l*l+c*c),1),d=o[2],h=o[3],f=Math.max(Math.sqrt(d*d+h*h),1);if(e instanceof HTMLElement||!e.data)r=e;else{s=this.cachedCanvases.getCanvas("inlineImage",i,n);var p=s.context;t(p,e),r=s.canvas}for(var m=i,v=n,g="prescale1";u>2&&m>1||f>2&&v>1;){var y=m,b=v;u>2&&m>1&&(y=Math.ceil(m/2),u/=m/y),f>2&&v>1&&(b=Math.ceil(v/2),f/=v/b),s=this.cachedCanvases.getCanvas(g,y,b),p=s.context,p.clearRect(0,0,y,b),p.drawImage(r,0,0,m,v,0,0,y,b),r=s.canvas,m=y,v=b,g="prescale1"===g?"prescale2":"prescale1"}if(a.drawImage(r,0,0,m,v,0,-n,i,n),this.imageLayer){var _=this.getCanvasPosition(0,-n);this.imageLayer.appendImage({imgData:e,left:_[0],top:_[1],width:i/o[0],height:n/o[3]})}this.restore()},paintInlineImageXObjectGroup:function(e,i){var n=this.ctx,a=e.width,r=e.height,s=this.cachedCanvases.getCanvas("inlineImage",a,r),o=s.context;t(o,e);for(var l=0,c=i.length;l<c;l++){var u=i[l];if(n.save(),n.transform.apply(n,u.transform),n.scale(1,-1),n.drawImage(s.canvas,u.x,u.y,u.w,u.h,0,-1,1,1),this.imageLayer){var d=this.getCanvasPosition(u.x,u.y);this.imageLayer.appendImage({imgData:e,left:d[0],top:d[1],width:a,height:r})}n.restore()}},paintSolidColorImageMask:function(){this.ctx.fillRect(0,0,1,1)},paintXObject:function(){C("Unsupported 'paintXObject' command.")},markPoint:function(e){},markPointProps:function(e,t){},beginMarkedContent:function(e){},beginMarkedContentProps:function(e,t){},endMarkedContent:function(){},beginCompat:function(){},endCompat:function(){},consumePath:function(){var e=this.ctx;this.pendingClip&&(this.pendingClip===V?void 0!==e.mozFillRule?(e.mozFillRule="evenodd",e.clip(),e.mozFillRule="nonzero"):e.clip("evenodd"):e.clip(),this.pendingClip=null),e.beginPath()},getSinglePixelWidth:function(e){if(null===this.cachedGetSinglePixelWidth){this.ctx.save();var t=this.ctx.mozCurrentTransformInverse;this.ctx.restore(),this.cachedGetSinglePixelWidth=Math.sqrt(Math.max(t[0]*t[0]+t[1]*t[1],t[2]*t[2]+t[3]*t[3]))}return this.cachedGetSinglePixelWidth},getCanvasPosition:function(e,t){var i=this.ctx.mozCurrentTransform;return[i[0]*e+i[2]*t+i[4],i[1]*e+i[3]*t+i[5]]}};for(var U in d)e.prototype[d[U]]=e.prototype[U];return e}();e.CanvasGraphics=R,e.createScratchCanvas=r}),function(e,t){t(e.pdfjsDisplayAPI={},e.pdfjsSharedUtil,e.pdfjsDisplayFontLoader,e.pdfjsDisplayCanvas,e.pdfjsDisplayMetadata,e.pdfjsDisplayDOMUtils)}(this,function(e,r,s,o,l,c,u){function d(e,t,i,n){var a=new Y;arguments.length>1&&k("getDocument is called with pdfDataRangeTransport, passwordCallback or progressCallback argument"),t&&(t instanceof X||(t=Object.create(t),t.length=e.length,t.initialData=e.initialData,t.abort||(t.abort=function(){})),e=Object.create(e),e.range=t),a.onPassword=i||null,a.onProgress=n||null;var r;"string"==typeof e?r={url:e}:I(e)?r={data:e}:e instanceof X?r={range:e}:("object"!=typeof e&&M("Invalid parameter in getDocument, need either Uint8Array, string or a parameter object"),e.url||e.data||e.range||M("Invalid 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destroyed")):(t.disableAutoFetch=z("disableAutoFetch"),t.disableStream=z("disableStream"),t.chunkedViewerLoading=!!i,i&&(t.length=i.length,t.initialData=i.initialData),e.messageHandler.sendWithPromise("GetDocRequest",{docId:n,source:t,disableRange:z("disableRange"),maxImageSize:z("maxImageSize"),cMapUrl:z("cMapUrl"),cMapPacked:z("cMapPacked"),disableFontFace:z("disableFontFace"),disableCreateObjectURL:z("disableCreateObjectURL"),postMessageTransfers:z("postMessageTransfers")&&!U}).then(function(t){if(e.destroyed)throw new Error("Worker was destroyed");return t}))}var f,p=r.InvalidPDFException,m=r.MessageHandler,v=r.MissingPDFException,g=r.PageViewport,y=r.PasswordResponses,b=r.PasswordException,_=r.StatTimer,x=r.UnexpectedResponseException,C=r.UnknownErrorException,w=r.Util,S=r.createPromiseCapability,M=r.error,k=r.deprecated,A=r.getVerbosityLevel,T=r.info,E=r.isInt,D=r.isArray,I=r.isArrayBuffer,P=r.isSameOrigin,N=r.loadJpegStream,O=r.stringToBytes,F=r.globalScope,L=r.warn,j=s.FontFaceObject,R=s.FontLoader,$=o.CanvasGraphics,B=o.createScratchCanvas,H=l.Metadata,z=c.getDefaultSetting,W=65536,V=!1,U=!1,G=!1;"undefined"==typeof window&&(V=!0,G=!0),G=!0,"undefined"!=typeof requirejs&&requirejs.toUrl&&(f=requirejs.toUrl("pdfjs-dist/build/pdf.worker.js"));var J="undefined"!=typeof requirejs&&requirejs.load,q=G?function(e){i.e(1,function(){var t=i(94);e(t.WorkerMessageHandler)})}:J?function(e){requirejs(["pdfjs-dist/build/pdf.worker"],function(t){e(t.WorkerMessageHandler)})}:null,Y=function(){function e(){this._capability=S(),this._transport=null,this._worker=null,this.docId="d"+t++,this.destroyed=!1,this.onPassword=null,this.onProgress=null,this.onUnsupportedFeature=null}var t=0;return e.prototype={get promise(){return this._capability.promise},destroy:function(){this.destroyed=!0;var e=this._transport?this._transport.destroy():Promise.resolve();return e.then(function(){this._transport=null,this._worker&&(this._worker.destroy(),this._worker=null)}.bind(this))},then:function(e,t){return this.promise.then.apply(this.promise,arguments)}},e}(),X=function(){function e(e,t){this.length=e,this.initialData=t,this._rangeListeners=[],this._progressListeners=[],this._progressiveReadListeners=[],this._readyCapability=S()}return e.prototype={addRangeListener:function(e){this._rangeListeners.push(e)},addProgressListener:function(e){this._progressListeners.push(e)},addProgressiveReadListener:function(e){this._progressiveReadListeners.push(e)},onDataRange:function(e,t){for(var i=this._rangeListeners,n=0,a=i.length;n<a;++n)i[n](e,t)},onDataProgress:function(e){this._readyCapability.promise.then(function(){for(var t=this._progressListeners,i=0,n=t.length;i<n;++i)t[i](e)}.bind(this))},onDataProgressiveRead:function(e){this._readyCapability.promise.then(function(){for(var t=this._progressiveReadListeners,i=0,n=t.length;i<n;++i)t[i](e)}.bind(this))},transportReady:function(){this._readyCapability.resolve()},requestDataRange:function(e,t){throw new Error("Abstract method PDFDataRangeTransport.requestDataRange")},abort:function(){}},e}(),K=function(){function e(e,t,i){this.pdfInfo=e,this.transport=t,this.loadingTask=i}return e.prototype={get numPages(){return this.pdfInfo.numPages},get fingerprint(){return this.pdfInfo.fingerprint},getPage:function(e){return this.transport.getPage(e)},getPageIndex:function(e){return this.transport.getPageIndex(e)},getDestinations:function(){return this.transport.getDestinations()},getDestination:function(e){return this.transport.getDestination(e)},getPageLabels:function(){return this.transport.getPageLabels()},getAttachments:function(){return this.transport.getAttachments()},getJavaScript:function(){return this.transport.getJavaScript()},getOutline:function(){return this.transport.getOutline()},getMetadata:function(){return this.transport.getMetadata()},getData:function(){return this.transport.getData()},getDownloadInfo:function(){return this.transport.downloadInfoCapability.promise},getStats:function(){return this.transport.getStats()},cleanup:function(){this.transport.startCleanup()},destroy:function(){return this.loadingTask.destroy()}},e}(),Q=function(){function e(e,t,i){this.pageIndex=e,this.pageInfo=t,this.transport=i,this.stats=new _,this.stats.enabled=z("enableStats"),this.commonObjs=i.commonObjs,this.objs=new te,this.cleanupAfterRender=!1,this.pendingCleanup=!1,this.intentStates=Object.create(null),this.destroyed=!1}return e.prototype={get pageNumber(){return this.pageIndex+1},get rotate(){return this.pageInfo.rotate},get ref(){return this.pageInfo.ref},get view(){return this.pageInfo.view},getViewport:function(e,t){return arguments.length<2&&(t=this.rotate),new g(this.view,e,t,0,0)},getAnnotations:function(e){var t=e&&e.intent||null;return this.annotationsPromise&&this.annotationsIntent===t||(this.annotationsPromise=this.transport.getAnnotations(this.pageIndex,t),this.annotationsIntent=t),this.annotationsPromise},render:function(e){function t(e){var t=r.renderTasks.indexOf(s);t>=0&&r.renderTasks.splice(t,1),l.cleanupAfterRender&&(l.pendingCleanup=!0),l._tryCleanup(),e?s.capability.reject(e):s.capability.resolve(),i.timeEnd("Rendering"),i.timeEnd("Overall")}var i=this.stats;i.time("Overall"),this.pendingCleanup=!1;var n="print"===e.intent?"print":"display",a=e.renderInteractiveForms===!0;this.intentStates[n]||(this.intentStates[n]=Object.create(null));var r=this.intentStates[n];r.displayReadyCapability||(r.receivingOperatorList=!0,r.displayReadyCapability=S(),r.operatorList={fnArray:[],argsArray:[],lastChunk:!1},this.stats.time("Page Request"),this.transport.messageHandler.send("RenderPageRequest",{pageIndex:this.pageNumber-1,intent:n,renderInteractiveForms:a}));var s=new ne(t,e,this.objs,this.commonObjs,r.operatorList,this.pageNumber);s.useRequestAnimationFrame="print"!==n,r.renderTasks||(r.renderTasks=[]),r.renderTasks.push(s);var o=s.task;e.continueCallback&&(k("render is used with continueCallback parameter"),o.onContinue=e.continueCallback);var l=this;return r.displayReadyCapability.promise.then(function(e){return l.pendingCleanup?void t():(i.time("Rendering"),s.initializeGraphics(e),void s.operatorListChanged())},function(e){t(e)}),o},getOperatorList:function(){function e(){if(n.operatorList.lastChunk){n.opListReadCapability.resolve(n.operatorList);var e=n.renderTasks.indexOf(i);e>=0&&n.renderTasks.splice(e,1)}}var t="oplist";this.intentStates[t]||(this.intentStates[t]=Object.create(null));var i,n=this.intentStates[t];return n.opListReadCapability||(i={},i.operatorListChanged=e,n.receivingOperatorList=!0,n.opListReadCapability=S(),n.renderTasks=[],n.renderTasks.push(i),n.operatorList={fnArray:[],argsArray:[],lastChunk:!1},this.transport.messageHandler.send("RenderPageRequest",{pageIndex:this.pageIndex,intent:t})),n.opListReadCapability.promise},getTextContent:function(e){return this.transport.messageHandler.sendWithPromise("GetTextContent",{pageIndex:this.pageNumber-1,normalizeWhitespace:!(!e||e.normalizeWhitespace!==!0),combineTextItems:!e||e.disableCombineTextItems!==!0})},_destroy:function(){this.destroyed=!0,this.transport.pageCache[this.pageIndex]=null;var e=[];return Object.keys(this.intentStates).forEach(function(t){if("oplist"!==t){var i=this.intentStates[t];i.renderTasks.forEach(function(t){var i=t.capability.promise.catch(function(){});e.push(i),t.cancel()})}},this),this.objs.clear(),this.annotationsPromise=null,this.pendingCleanup=!1,Promise.all(e)},destroy:function(){k("page destroy method, use cleanup() instead"),this.cleanup()},cleanup:function(){this.pendingCleanup=!0,this._tryCleanup()},_tryCleanup:function(){this.pendingCleanup&&!Object.keys(this.intentStates).some(function(e){var t=this.intentStates[e];return 0!==t.renderTasks.length||t.receivingOperatorList},this)&&(Object.keys(this.intentStates).forEach(function(e){delete this.intentStates[e]},this),this.objs.clear(),this.annotationsPromise=null,this.pendingCleanup=!1)},_startRenderPage:function(e,t){var i=this.intentStates[t];i.displayReadyCapability&&i.displayReadyCapability.resolve(e)},_renderPageChunk:function(e,t){var i,n,a=this.intentStates[t];for(i=0,n=e.length;i<n;i++)a.operatorList.fnArray.push(e.fnArray[i]),a.operatorList.argsArray.push(e.argsArray[i]);for(a.operatorList.lastChunk=e.lastChunk,i=0;i<a.renderTasks.length;i++)a.renderTasks[i].operatorListChanged();e.lastChunk&&(a.receivingOperatorList=!1,this._tryCleanup())}},e}(),Z=function(){function e(){return"undefined"!=typeof f?f:z("workerSrc")?z("workerSrc"):a?a.replace(/\.js$/i,".worker.js"):void M("No PDFJS.workerSrc specified")}function t(){if(!s){s=S();var t=q||function(t){w.loadScript(e(),function(){t(window.pdfjsDistBuildPdfWorker.WorkerMessageHandler)})};t(s.resolve)}return s.promise}function i(e){this._listeners=[],this._defer=e,this._deferred=Promise.resolve(void 0)}function n(e){var t="importScripts('"+e+"');";return URL.createObjectURL(new Blob([t]))}function r(e){this.name=e,this.destroyed=!1,this._readyCapability=S(),this._port=null,this._webWorker=null,this._messageHandler=null,this._initialize()}var s,o=0;return i.prototype={postMessage:function(e,t){function i(e){if("object"!=typeof e||null===e)return e;if(n.has(e))return n.get(e);var a,r;if((r=e.buffer)&&I(r)){var s=t&&t.indexOf(r)>=0;return a=e===r?e:s?new e.constructor(r,e.byteOffset,e.byteLength):new e.constructor(e),n.set(e,a),a}a=D(e)?[]:{},n.set(e,a);for(var o in e){for(var l,c=e;!(l=Object.getOwnPropertyDescriptor(c,o));)c=Object.getPrototypeOf(c);"undefined"!=typeof l.value&&"function"!=typeof l.value&&(a[o]=i(l.value))}return a}if(!this._defer)return void this._listeners.forEach(function(t){t.call(this,{data:e})},this);var n=new WeakMap,a={data:i(e)};this._deferred.then(function(){this._listeners.forEach(function(e){e.call(this,a)},this)}.bind(this))},addEventListener:function(e,t){this._listeners.push(t)},removeEventListener:function(e,t){var i=this._listeners.indexOf(t);this._listeners.splice(i,1)},terminate:function(){this._listeners=[]}},r.prototype={get promise(){return this._readyCapability.promise},get port(){return this._port},get messageHandler(){return this._messageHandler},_initialize:function(){if(!V&&!z("disableWorker")&&"undefined"!=typeof Worker){var t=e();try{P(window.location.href,t)||(t=n(new URL(t,window.location).href));var i=new Worker(t),a=new m("main","worker",i),r=function(){i.removeEventListener("error",s),a.destroy(),i.terminate(),this.destroyed?this._readyCapability.reject(new Error("Worker was destroyed")):this._setupFakeWorker()}.bind(this),s=function(e){this._webWorker||r()}.bind(this);i.addEventListener("error",s),a.on("test",function(e){if(i.removeEventListener("error",s),this.destroyed)return void r();var t=e&&e.supportTypedArray;t?(this._messageHandler=a,this._port=i,this._webWorker=i,e.supportTransfers||(U=!0),this._readyCapability.resolve(),a.send("configure",{verbosity:A()})):(this._setupFakeWorker(),a.destroy(),i.terminate())}.bind(this)),a.on("console_log",function(e){console.log.apply(console,e)}),a.on("console_error",function(e){console.error.apply(console,e)}),a.on("ready",function(e){if(i.removeEventListener("error",s),this.destroyed)return void r();try{o()}catch(e){this._setupFakeWorker()}}.bind(this));var o=function(){var e=z("postMessageTransfers")&&!U,t=new Uint8Array([e?255:0]);try{a.send("test",t,[t.buffer])}catch(e){T("Cannot use postMessage transfers"),t[0]=0,a.send("test",t)}};return void o()}catch(e){T("The worker has been disabled.")}}this._setupFakeWorker()},_setupFakeWorker:function(){V||z("disableWorker")||(L("Setting up fake worker."),V=!0),t().then(function(e){if(this.destroyed)return void this._readyCapability.reject(new Error("Worker was destroyed"));var t=Uint8Array!==Float32Array,n=new i(t);this._port=n;var a="fake"+o++,r=new m(a+"_worker",a,n);e.setup(r,n);var s=new m(a,a+"_worker",n);this._messageHandler=s,this._readyCapability.resolve()}.bind(this))},destroy:function(){this.destroyed=!0,this._webWorker&&(this._webWorker.terminate(),this._webWorker=null),this._port=null,this._messageHandler&&(this._messageHandler.destroy(),this._messageHandler=null)}},r}(),ee=function(){function e(e,t,i){this.messageHandler=e,this.loadingTask=t,this.pdfDataRangeTransport=i,this.commonObjs=new te,this.fontLoader=new R(t.docId),this.destroyed=!1,this.destroyCapability=null,this.pageCache=[],this.pagePromises=[],this.downloadInfoCapability=S(),this.setupMessageHandler()}return e.prototype={destroy:function(){if(this.destroyCapability)return this.destroyCapability.promise;this.destroyed=!0,this.destroyCapability=S();var e=[];this.pageCache.forEach(function(t){t&&e.push(t._destroy())}),this.pageCache=[],this.pagePromises=[];var t=this,i=this.messageHandler.sendWithPromise("Terminate",null);return e.push(i),Promise.all(e).then(function(){t.fontLoader.clear(),t.pdfDataRangeTransport&&(t.pdfDataRangeTransport.abort(),t.pdfDataRangeTransport=null),t.messageHandler&&(t.messageHandler.destroy(),t.messageHandler=null),t.destroyCapability.resolve()},this.destroyCapability.reject),this.destroyCapability.promise},setupMessageHandler:function(){function e(e){t.send("UpdatePassword",e)}var t=this.messageHandler,i=this.pdfDataRangeTransport;i&&(i.addRangeListener(function(e,i){t.send("OnDataRange",{begin:e,chunk:i})}),i.addProgressListener(function(e){t.send("OnDataProgress",{loaded:e})}),i.addProgressiveReadListener(function(e){t.send("OnDataRange",{chunk:e})}),t.on("RequestDataRange",function(e){i.requestDataRange(e.begin,e.end)},this)),t.on("GetDoc",function(e){var t=e.pdfInfo;this.numPages=e.pdfInfo.numPages;var i=this.loadingTask,n=new K(t,this,i);this.pdfDocument=n,i._capability.resolve(n)},this),t.on("NeedPassword",function(t){var i=this.loadingTask;return i.onPassword?i.onPassword(e,y.NEED_PASSWORD):void i._capability.reject(new b(t.message,t.code))},this),t.on("IncorrectPassword",function(t){var i=this.loadingTask;return i.onPassword?i.onPassword(e,y.INCORRECT_PASSWORD):void i._capability.reject(new b(t.message,t.code))},this),t.on("InvalidPDF",function(e){this.loadingTask._capability.reject(new p(e.message))},this),t.on("MissingPDF",function(e){this.loadingTask._capability.reject(new v(e.message))},this),t.on("UnexpectedResponse",function(e){this.loadingTask._capability.reject(new x(e.message,e.status))},this),t.on("UnknownError",function(e){this.loadingTask._capability.reject(new C(e.message,e.details))},this),t.on("DataLoaded",function(e){this.downloadInfoCapability.resolve(e)},this),t.on("PDFManagerReady",function(e){this.pdfDataRangeTransport&&this.pdfDataRangeTransport.transportReady()},this),t.on("StartRenderPage",function(e){if(!this.destroyed){var t=this.pageCache[e.pageIndex];t.stats.timeEnd("Page Request"),t._startRenderPage(e.transparency,e.intent)}},this),t.on("RenderPageChunk",function(e){if(!this.destroyed){var t=this.pageCache[e.pageIndex];t._renderPageChunk(e.operatorList,e.intent)}},this),t.on("commonobj",function(e){if(!this.destroyed){var t=e[0],i=e[1];if(!this.commonObjs.hasData(t))switch(i){case"Font":var n=e[2];if("error"in n){var a=n.error;L("Error during font loading: "+a),this.commonObjs.resolve(t,a);break}var r=null;z("pdfBug")&&F.FontInspector&&F.FontInspector.enabled&&(r={registerFont:function(e,t){F.FontInspector.fontAdded(e,t)}});var s=new j(n,{isEvalSuported:z("isEvalSupported"),disableFontFace:z("disableFontFace"),fontRegistry:r});this.fontLoader.bind([s],function(e){this.commonObjs.resolve(t,s)}.bind(this));break;case"FontPath":this.commonObjs.resolve(t,e[2]);break;default:M("Got unknown common object type "+i)}}},this),t.on("obj",function(e){if(!this.destroyed){var t,i=e[0],n=e[1],a=e[2],r=this.pageCache[n];if(!r.objs.hasData(i))switch(a){case"JpegStream":t=e[3],N(i,t,r.objs);break;case"Image":t=e[3],r.objs.resolve(i,t);var s=8e6;t&&"data"in t&&t.data.length>s&&(r.cleanupAfterRender=!0);break;default:M("Got unknown object type "+a)}}},this),t.on("DocProgress",function(e){if(!this.destroyed){var t=this.loadingTask;t.onProgress&&t.onProgress({loaded:e.loaded,total:e.total})}},this),t.on("PageError",function(e){if(!this.destroyed){var t=this.pageCache[e.pageNum-1],i=t.intentStates[e.intent];if(i.displayReadyCapability?i.displayReadyCapability.reject(e.error):M(e.error),i.operatorList){i.operatorList.lastChunk=!0;for(var n=0;n<i.renderTasks.length;n++)i.renderTasks[n].operatorListChanged()}}},this),t.on("UnsupportedFeature",function(e){if(!this.destroyed){var t=e.featureId,i=this.loadingTask;i.onUnsupportedFeature&&i.onUnsupportedFeature(t),ae.notify(t)}},this),t.on("JpegDecode",function(e){if(this.destroyed)return Promise.reject(new Error("Worker was destroyed"));var t=e[0],i=e[1];return 3!==i&&1!==i?Promise.reject(new Error("Only 3 components or 1 component can be returned")):new Promise(function(e,n){var a=new Image;a.onload=function(){var t=a.width,n=a.height,r=t*n,s=4*r,o=new Uint8Array(r*i),l=B(t,n),c=l.getContext("2d");c.drawImage(a,0,0);var u,d,h=c.getImageData(0,0,t,n).data;if(3===i)for(u=0,d=0;u<s;u+=4,d+=3)o[d]=h[u],o[d+1]=h[u+1],o[d+2]=h[u+2];else if(1===i)for(u=0,d=0;u<s;u+=4,d++)o[d]=h[u];e({data:o,width:t,height:n})},a.onerror=function(){n(new Error("JpegDecode failed to load image"))},a.src=t})},this)},getData:function(){return this.messageHandler.sendWithPromise("GetData",null)},getPage:function(e,t){if(!E(e)||e<=0||e>this.numPages)return Promise.reject(new Error("Invalid page request"));var i=e-1;if(i in this.pagePromises)return this.pagePromises[i];var n=this.messageHandler.sendWithPromise("GetPage",{pageIndex:i}).then(function(e){if(this.destroyed)throw new Error("Transport destroyed");var t=new Q(i,e,this);return this.pageCache[i]=t,t}.bind(this));return this.pagePromises[i]=n,n},getPageIndex:function(e){return this.messageHandler.sendWithPromise("GetPageIndex",{ref:e}).catch(function(e){return Promise.reject(new Error(e))})},getAnnotations:function(e,t){return this.messageHandler.sendWithPromise("GetAnnotations",{pageIndex:e,intent:t})},getDestinations:function(){return this.messageHandler.sendWithPromise("GetDestinations",null)},getDestination:function(e){return this.messageHandler.sendWithPromise("GetDestination",{id:e})},getPageLabels:function(){return this.messageHandler.sendWithPromise("GetPageLabels",null)},getAttachments:function(){return this.messageHandler.sendWithPromise("GetAttachments",null)},getJavaScript:function(){return this.messageHandler.sendWithPromise("GetJavaScript",null)},getOutline:function(){return this.messageHandler.sendWithPromise("GetOutline",null)},getMetadata:function(){return this.messageHandler.sendWithPromise("GetMetadata",null).then(function(e){return{info:e[0],metadata:e[1]?new H(e[1]):null}})},getStats:function(){return this.messageHandler.sendWithPromise("GetStats",null)},startCleanup:function(){this.messageHandler.sendWithPromise("Cleanup",null).then(function(){for(var e=0,t=this.pageCache.length;e<t;e++){var i=this.pageCache[e];i&&i.cleanup()}this.commonObjs.clear(),this.fontLoader.clear()}.bind(this))}},e}(),te=function(){function e(){this.objs=Object.create(null)}return e.prototype={ensureObj:function(e){if(this.objs[e])return this.objs[e];var t={capability:S(),data:null,resolved:!1};return this.objs[e]=t,t},get:function(e,t){if(t)return this.ensureObj(e).capability.promise.then(t),null;var i=this.objs[e];return i&&i.resolved||M("Requesting object that isn't resolved yet "+e),i.data},resolve:function(e,t){var i=this.ensureObj(e);i.resolved=!0,i.data=t,i.capability.resolve(t)},isResolved:function(e){var t=this.objs;return!!t[e]&&t[e].resolved},hasData:function(e){return this.isResolved(e)},getData:function(e){var t=this.objs;return t[e]&&t[e].resolved?t[e].data:null},clear:function(){this.objs=Object.create(null)}},e}(),ie=function(){function e(e){this._internalRenderTask=e,this.onContinue=null}return e.prototype={get promise(){return this._internalRenderTask.capability.promise},cancel:function(){this._internalRenderTask.cancel()},then:function(e,t){return this.promise.then.apply(this.promise,arguments)}},e}(),ne=function(){function e(e,t,i,n,a,r){this.callback=e,this.params=t,this.objs=i,this.commonObjs=n,this.operatorListIdx=null,this.operatorList=a,this.pageNumber=r,this.running=!1,this.graphicsReadyCallback=null,this.graphicsReady=!1,this.useRequestAnimationFrame=!1,this.cancelled=!1,this.capability=S(),this.task=new ie(this),this._continueBound=this._continue.bind(this),this._scheduleNextBound=this._scheduleNext.bind(this),this._nextBound=this._next.bind(this)}return e.prototype={initializeGraphics:function(e){if(!this.cancelled){z("pdfBug")&&F.StepperManager&&F.StepperManager.enabled&&(this.stepper=F.StepperManager.create(this.pageNumber-1),this.stepper.init(this.operatorList),this.stepper.nextBreakPoint=this.stepper.getNextBreakPoint());var t=this.params;this.gfx=new 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project")])])}]}},function(e,t,i){i(99);var n=i(14)(i(101),i(102),"data-v-0ca0bba8",null);e.exports=n.exports},function(e,t,i){var n=i(100);"string"==typeof n&&(n=e.id,n,""),n.locals&&(e.exports=n.locals);i(12)("3d1973a8",n,!0)},function(e,t,i){t=e.exports=i(11)(),t.push([e.id,"#interlab .el-table[data-v-0ca0bba8]{display:table;margin:10px auto;text-align:center}#interlab ul[data-v-0ca0bba8]{padding-left:50px;padding-top:10px}#interlab img[data-v-0ca0bba8]{margin-top:20px;margin-left:auto;margin-right:auto;display:block}",""])},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}Object.defineProperty(t,"__esModule",{value:!0});var a=i(16),r=n(a);t.default={data:function(){return{tableData:[{name:"Negative control(BBa_R0040)"},{name:"Positive Control (BBa_I20270)"},{name:"Test Device 1 (BBa_J364000)"},{name:"Test Device 2 (BBa_J364001"},{name:"Test Device 3 (BBa_J364002"},{name:"Test Device 4 (BBa_J364003"},{name:"Test Device 5 (BBa_J364004"},{name:"Test Device 6 (BBa_J364005"}]}},components:{MyFooter:r.default}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"igem-page Notebook",attrs:{id:"interlab"}},[e._m(0),e._v(" "),i("div",{staticClass:"page-content",attrs:{id:"interlab-content"}},[e._m(1),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Materials and Methods")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("The measurement was done by carefully following the Plate Reader Protocol from https://2017.igem.org/Competition/InterLab_Study/Plate_Reader. ")]),e._v(" "),e._m(2),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Materials")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("InterLab Measurement Kit")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Eight devices to be tested:")]),e._v(" "),i("el-table",{staticStyle:{width:"30%"},attrs:{data:e.tableData}},[i("el-table-column",{attrs:{prop:"name"}})],1),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Bacteria strain: Escherichia coli DH5-alpha")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("LB medium with Chloramphenicol(25ug/mL)")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Plate reader: BioTek® Synergy H1")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Black 96 well plate with flat, transparent bottom")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Materials")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("OD600 reference point")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("OD600 reference point was obtained by measuring the Abs600 of H2O and LUDOX HS-40 from InterLab Measurement Kit, followed by data processing. ")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Fluorescein standard curve")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Fluorescein standard curve was obtained by serial dilution of the fluorescein solution followed by measurements using plate reader. ")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("Cell measurements")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Plasmids of each device was re-suspended from Distribution Kit and used to transform Escherichia coli DH5-alpha. ")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("2 colonies from each plate was picked and inoculated in 5ml LB medium with Chloramphenicol.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("The overnight cultures were each diluted to a target OD600 of 0.02 in 12ml LB medium. The diluted cultures were incubated at 37℃ and sampled at 0, 2, 4, 6 hours post incubation. The OD600 and fluorescence intensity was measured at each time point.")])],1),e._v(" "),e._m(3),e._v(" "),e._m(4),e._v(" "),e._m(5)]),e._v(" "),i("my-footer")],1)},staticRenderFns:[function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-header",attrs:{id:"interlab-header"}},[i("p",{staticClass:"page-title"},[e._v("Interlab")]),e._v(" "),i("p",{staticClass:"page-subheader"},[e._v("Our work and results for Interlab measurement")])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Introduction")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Reliable and repeatable measurement is a key component to all engineering disciplines. The same holds true for synthetic biology, which has also been called engineering biology. However, the ability to repeat measurements in different labs has been difficult. To solve this problem, the InterLab Study attempts to establish a detailed protocol and data analysis form that yields absolute units for measuring GFP in a plate reader.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Over the past three years, InterLab participants from all over the world has provided enormous amount of data, advancing the frontiers of synthetic biology. However, more data is required to improve the protocol.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("This year, members from SYSU-CHINA are excited to participate in the fourth InterLab, trying our utmost to contribute to the synthetic biology community. ")])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("p",{staticClass:"card-text"},[e._v("Our detailed protocol can be found "),i("a",{attrs:{href:"https://2017.igem.org/Team:SYSU-CHINA#/Protocols"}},[e._v("here")]),e._v(".")])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Results")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("1. Fluorescein standard curve")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("During the determination of fluorescein standard curve, we observed that the fluorescence intensity tends to saturate at high concentration, while becomes less accurate at low concentration. Considering the fact that all our cell fluorescence data did not exceed 2000, we exclude the last two data point, and use linear regression to determine the standard curve, which we believe is more accurate. The following graphs show linear regression before and after excluding the last data point.")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 1. Fluorescence Standard Curve with all data points using linear regression method. Note that the staturated data points at high concentration affect the curve’s accuracy")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 2. Fluorescence Standard Curve without data points at highest concentration using linear regression method. The curve’s accuracy is greatly improved")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("2. Cell Measurement")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("2.1 Colony PCR")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("To determine if each culture was transformed with the right plasmid, we performed a colony PCR using the overnight cultures as templates and sequencing primers VF2 and VR as primers. The gel electrophoresis result below showed that the bands were of the right size. However, since all devices but negative control differed only in their promoter and RBS, PCR reaction was not adequate to distinguish different devices, thus additional sequencing should be performed.")]),e._v(" "),i("img",{attrs:{src:"",width:"80%"}}),e._v(" "),i("figure",[e._v("Figure 3. gel analysis result of colony PCR using VF2 and VR as primers")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("2.2 OD600 measurements")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("The following graph shows the OD600 of each device at each time point. All samples grew steadily with a trend that the stronger the promoters and RBS were, the slower the cultures grew. The two cultures transformed with test device 1 grew rather slowly compared to others, possibly resulting from the heavy expression burden of the test device.")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("figure",[e._v("Figure 4. line chart of different cultures’ OD600 through the time course of measurement")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("2.3 Fluorescence measurements")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("The following graph shows the fluorescence intensity of each device at each time point. It is obvious that positive control displayed the strongest fluorescence, followed by test device 2 and device 4. Although we expected test device 1, which possessed strong promoter and RBS, to have the most intensive fluorescence, the data we obtained showed otherwise. The fact that fluorescence of device 1 was weaker than device 2, which shared the same RBS but only had a medium strength promoter J23106, shocked us. We reasoned that the low fluorescence might be resulted from low cell density. Considering the fact that the cultures differed in their cell density, it is not feasible to compare promoter or RBS strength by directly comparing the overall fluorescence.")]),e._v(" "),i("img",{attrs:{src:"",width:"80%"}}),e._v(" "),i("figure",[e._v("Figure 5. line chart of different cultures’ flurescence intensity through the time course of measurement")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("2.4 Fluorescence Intensity(FI)/OD600")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("To exclude the influence of cell density, we calculated FI/OD600, which represented average fluorescence of per OD cells in the medium. It is obvious that although device 1 displayed low overall FI, the FI/OD600 was comparable to that of positive control, device 2 and device 4. The negative control, device 3, 5 and 6 displayed a considerably lower FI/OD600. Thus, device 1 was still a strong expression device. However, the strong expression from device 1 strongly inhibited cell growth. Therefore a combination of J23101 and B0034 may not be feasible in terms of industrial application.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("In addition, Comparison between device 2 and device 5, which shared the same promoter but had different RBS, indicated that B0034 was a stronger RBS than BCD2. Comparison among device 4, 5, 6, which shared the same RBS but had different promoters, suggested that J23101 was the strongest promoter, followed by J23106 and finally J23117.")]),e._v(" "),i("img",{attrs:{src:"",width:"80%"}}),e._v(" "),i("figure",[e._v("Figure 6. histogram of different cultures’ FI/OD600 at each time point")]),e._v(" "),i("p",{staticClass:"card-subsubheader"},[e._v("2.5 Direct observation of the fluorescence")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("After the measurements, we decided to streak all of the devices on one plate, so we were able to compare fluorescence intensity by direct observation. After culturing for 18 hours, we imaged the plate under the blue light with filter glass. Positive device, test device 1 and 2 fluoresce intensively while others quite weakly. Comparison among device 1 to 3, and device 4 to 6, suggested that promoter J23101 was the strongest, followed by J23106. Comparison between device 1, 2 and device 4, 5 respectively indicated that RBS B0034 was stronger than BCD2. This observation was in agreement with the previous plate reader data.")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("In contrast to the data shown before, test device 1 glowed quite strongly, possibly resulting from a longer growth time, when all the cultures ended up having a similar OD.")]),e._v(" "),i("img",{attrs:{src:"",width:"40%"}}),e._v(" "),i("figure",[e._v("Figure 7. image result of different cultures’ fluorescence")])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Disscusion")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Aiming to contribute to the synthetic biology community, we, SYSU-CHINA, devoted ourselves to the InterLab Study. After days of hard work, we gathered enough raw data, which we submitted to the iGEM HQ. Meanwhile, we used our data to draw the following conclusions:")]),e._v(" "),i("ul",[i("li",[i("p",[e._v("The strength of promoters decreases in the order J23101, J23106 and J23117.")])]),e._v(" "),i("li",[i("p",[e._v("The RBS B0034 is stronger than BCD2.")])]),e._v(" "),i("li",[i("p",[e._v("Cultures with higher GFP expression tend to grow slower.")])])]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("We also discovered that at high concentration the fluorescence intensity of fluorescein is prone to saturation and lost linearity, while at low concentration, the intensity could vary greatly and also lost linearity, both of which lead to inaccurate standard curve. So we suggested that data points at the highest concentration (far exceed cell measurement data) be excluded and linear regression be used to minimize errors. ")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("This year, our team’s project focused on mammalian cell lines and animal models. The InterLab Study brought us a whole new experience of measuring bacteria optical density and fluorescence. Not only did we gain experiences and practice our lab skills, but we also had fun!")])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("References")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Beal, J. et al. Reproducibility of Fluorescent Expression from Engineered Biological Constructs in E. coli. PloS one 11, e0150182, doi:10.1371/journal.pone.0150182 (2016).")])])}]}},function(e,t,i){i(104);var n=i(14)(i(106),i(107),"data-v-4cf22d38",null);e.exports=n.exports},function(e,t,i){var n=i(105);"string"==typeof n&&(n=e.id,n,""),n.locals&&(e.exports=n.locals);i(12)("743eb760",n,!0)},function(e,t,i){t=e.exports=i(11)(),t.push([e.id,"#parts img[data-v-4cf22d38]{margin-top:20px;margin-left:auto;margin-right:auto;display:block}",""])},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}Object.defineProperty(t,"__esModule",{value:!0});var a=i(16),r=n(a);t.default={components:{MyFooter:r.default}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"igem-page Parts",attrs:{id:"parts"}},[e._m(0),e._v(" "),e._m(1),e._v(" "),i("my-footer")],1)},staticRenderFns:[function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-header",attrs:{id:"parts-header"}},[i("p",{staticClass:"page-title"},[e._v("Parts")]),e._v(" "),i("p",{staticClass:"page-subheader"},[e._v("General information about the new parts we submitted")])])},function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"page-content",attrs:{id:"parts-content"}},[i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-text"},[e._v("This year, SYSU-CHINA attempted to create engineered bone marrow stromal cells that can secrete various growth factors to accelerate wound healing. However, when we checked the registry, we were disappointed to find that there were few available growth factors for us to use. Aiming to benefit the iGEM community, we standardized all the growth factors in our project by cloning the sequences into the standard plasmid backbone pSB1C3, and submitted them to the iGEM registry. To ensure the parts’ quality, we sequenced the part using VF2 as primer before submitting the plasmids. Hopefully, teams in the future that are ambitious to conduct projects on wound healing will find our parts useful.")])]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("Basic Parts")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("basic fibroblast growth factor(bFGF)(BBa_K2298000, submitted as the favorite basic part）")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Fibroblast growth factors(FGFs), originally known for their capability of promoting fibroblast proliferation, are a family of growth factors that has shown great potentials on tissue repair. Human FGFs consist of 22 members. FGFs exert their roles by binding to the transmembrane tyrosine kinase receptors, FGF receptors(FGFRs), therefore triggering downstream signaling cascades including RAS/MAP Kinase pathway, PI3 Kinase/AKT pathway and PLC-gamma pathway. The signaling then stimulates a wide range of cellular responses, such as cell proliferation, cell migration, cell differentiation and angiogenesis. (see review"),i("sup",[i("a",{attrs:{href:"#Parts/#reference"}},[e._v("1")])]),e._v(")")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Due to their ability to induce fibroblast proliferation and angiogenesis, FGFs have been studied extensively in terms of tissue repair in diverse kinds of tissue, with basic fibroblast growth factor(bFGF) being the most used FGF in wound healing(see review"),i("sup",[i("a",{attrs:{href:"#Parts/#reference"}},[e._v("1")])]),e._v("). bFGF is thought to be an initiator of the wound healing process, reaching its highest concentration soon after injury and then declining to serum level"),i("sup",[i("a",{attrs:{href:"#Parts/#reference"}},[e._v("2")])]),e._v(". bFGF may also possess the anti-scarring effect during wound healing"),i("sup",[i("a",{attrs:{href:"#Parts/#reference"}},[e._v("3")])]),e._v(", which makes it an potential candidate for scar-free healing applications. ")]),e._v(" "),i("a",{attrs:{href:"http://parts.igem.org/Part:BBa_K2298000"}},[e._v("(see more details about this part) ")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Vascular endothelial growth factor A(VEGFA) 121（BBa_K2298001, submitted as improved part）")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Vascular endothelial growth factor (VEGF) represents a family of homodimer glycoproteins which plays a critical role for vasculogenesis, lymphangiogenesis as well as angiogenesis. In humans, VEGF-A exists in six different isoforms, VEGF-A121, VEGF-A145, VEGF-A165, VEGF-A183, VEGF-A189 and VEGF-A206, as a result of alternative splicing of the precursor mRNA. VEGF-A121, the smallest variant, diffuses freely due to the lack of heparin binding site while others interact with extracellular matrix and cell surface heparan sulphate proteoglycans"),i("sup",[i("a",{attrs:{href:"#Parts/#reference"}},[e._v("4")])]),e._v(".")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("VEGFs stimulate cellular responses through binding to cell surface receptor tyrosine kinases, namely VEGFR-1, VEGFR-2 and VEGFR-3, therefore triggering downstream signaling cascades. The responses include endothelial cell proliferation, migration, survival and vascular permeability alternation"),i("sup",[i("a",{attrs:{href:"#Parts/#reference"}},[e._v("4")])]),e._v(". In addition, VEGFs stimulate keratinocytes and fibroblasts to migrate towards the wounded site, which also contributes to wound healing"),i("sup",[i("a",{attrs:{href:"#Parts/#reference"}},[e._v("5")])]),e._v(".")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("In a study on VEGFs’ effect on endometrial repair in severe intrauterine adhesion, VEGF expression and MVD in patients responding to therapy were significantly higher than those in patients non-responding to therapy, indicating a critical role of VEGF in the healing process of endometrial after surgery"),i("sup",[i("a",{attrs:{href:"#Parts/#reference"}},[e._v("6")])]),e._v(".")]),e._v(" "),i("a",{attrs:{href:"http://parts.igem.org/Part:BBa_K2298001"}},[e._v("(see more details about this part) ")]),e._v(" "),i("p",{staticClass:"card-subheader"},[e._v("Platelet-derived growth factor A(BBa_K2298002)")]),e._v(" "),i("img",{attrs:{src:"",width:"60%"}}),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Platelet-derived growth factors family consists of five members of homodimeric or heterodimeric protein. By binding to PDGFR-alpha or PDGFR-beta, two tyrosine kinase receptors, PDGFs trigger signaling cascades that regulate cellular behaviors, including chemotaxis, cell proliferation, survival and differentiation. It is believed that PDGFs play essential roles in diverse stages of wound healing."),i("sup",[i("a",{attrs:{href:"#Parts/#reference"}},[e._v("7")])])]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("Prior studies show that adding Platelet-derived growth factor (PDGF) directly to experimentally designed wounds enhances wound healing"),i("sup",[i("a",{attrs:{href:"#Parts/#reference"}},[e._v("8")])]),e._v(".")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v(""),i("sup",[i("a",{attrs:{href:"#Parts/#reference"}},[e._v("")])]),e._v("")]),e._v(" "),i("a",{attrs:{href:"http://parts.igem.org/Part:BBa_K2298002"}},[e._v("(see more details about this part) ")])]),e._v(" "),i("div",{staticClass:"content-card"},[i("p",{staticClass:"card-title"},[e._v("References")]),e._v(" "),i("a",{staticStyle:{"{display":"none"},attrs:{name:"Parts/#reference",id:"Parts/#reference"}}),e._v(" "),i("p",{staticClass:"card-text"},[e._v("1\tYun, Y. R. et al. Fibroblast growth factors: biology, function, and application for tissue regeneration. Journal of tissue engineering 2010, 218142, doi:10.4061/2010/218142 (2010).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("2\tNissen, N. N. et al. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. The American journal of pathology 152, 1445-1452 (1998).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("3\tSpyrou, G. E. & Naylor, I. L. The effect of basic fibroblast growth factor on scarring. British journal of plastic surgery 55, 275-282 (2002).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("4\tHolmes, K., Roberts, O. L., Thomas, A. M. & Cross, M. J. Vascular endothelial growth factor receptor-2: structure, function, intracellular signalling and therapeutic inhibition. Cellular signalling 19, 2003-2012, doi:10.1016/j.cellsig.2007.05.013 (2007).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("5\tBao, P. et al. The role of vascular endothelial growth factor in wound healing. The Journal of surgical research 153, 347-358, doi:10.1016/j.jss.2008.04.023 (2009).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("6\tChen, Y., Chang, Y. & Yao, S. Role of angiogenesis in endometrial repair of patients with severe intrauterine adhesion. International journal of clinical and experimental pathology 6, 1343-1350 (2013).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("7 Kaltalioglu, K. & Coskun-Cevher, S. A bioactive molecule in a complex wound healing process: platelet-derived growth factor. International journal of dermatology 54, 972-977, doi:10.1111/ijd.12731 (2015).")]),e._v(" "),i("p",{staticClass:"card-text"},[e._v("8\tRoss, R., Bowen-Pope, D. F. & Raines, E. W. Platelet-derived growth factor and its role in health and disease. Philosophical transactions of the Royal Society of London. Series B, Biological sciences 327, 155-169 (1990).")])])])}]}},function(e,t,i){i(109);var n=i(14)(i(111),i(117),"data-v-5795ebd4",null);e.exports=n.exports},function(e,t,i){var n=i(110);"string"==typeof n&&(n=e.id,n,""),n.locals&&(e.exports=n.locals);i(12)("a268a424",n,!0)},function(e,t,i){t=e.exports=i(11)(),t.push([e.id,"#team-carousel[data-v-5795ebd4]{margin-top:-30px}#teammembers-content[data-v-5795ebd4]{margin-top:30px}#teammembers-content .content-card>img[data-v-5795ebd4]{width:100%}.teammembers-card-title[data-v-5795ebd4]{display:table;font-size:20pt;font-weight:700;margin-bottom:20px;margin-left:auto;margin-right:auto;font-family:CenturyGothic}.content-card[data-v-5795ebd4]{font-family:CenturyGothic}.el-carousel__mask[data-v-5795ebd4]{background-color:#f0f0f0!important}.el-carousel__item[data-v-5795ebd4]:nth-child(2n),.el-carousel__item[data-v-5795ebd4]:nth-child(odd){background-color:#f0f0f0}",""])},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}Object.defineProperty(t,"__esModule",{value:!0});var a=i(21),r=n(a),s=i(112),o=n(s),l=i(16),c=n(l);t.default={data:function(){return{instructors:[{name:"Liu Feng",intro:"Primary PI. 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i={props:{mode:"out-in"},on:{beforeEnter:function(e){e.style.opacity=.2},enter:function(e){(0,s.addClass)(e,"el-opacity-transition"),e.style.opacity=1},afterEnter:function(e){(0,s.removeClass)(e,"el-opacity-transition"),e.style.opacity=""},beforeLeave:function(e){e.dataset||(e.dataset={}),(0,s.hasClass)(e,"el-menu--collapse")&&((0,s.removeClass)(e,"el-menu--collapse"),e.dataset.oldOverflow=e.style.overflow,e.dataset.scrollWidth=e.scrollWidth,(0,s.addClass)(e,"el-menu--collapse")),e.style.width=e.scrollWidth+"px",e.style.overflow="hidden"},leave:function(e){(0,s.hasClass)(e,"el-menu--collapse")?((0,s.addClass)(e,"horizontal-collapse-transition"),e.style.width=e.dataset.scrollWidth+"px"):((0,s.addClass)(e,"horizontal-collapse-transition"),e.style.width="64px")},afterLeave:function(e){(0,s.removeClass)(e,"horizontal-collapse-transition"),(0,s.hasClass)(e,"el-menu--collapse")?e.style.width=e.dataset.scrollWidth+"px":e.style.width="64px",e.style.overflow=e.dataset.oldOverflow}}};return 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n=i(5)(i(97),i(98),null,null,null);e.exports=n.exports},function(e,t){"use strict";t.__esModule=!0,t.default={name:"ElSwitch",props:{value:{type:[Boolean,String,Number],default:!1},disabled:{type:Boolean,default:!1},width:{type:Number,default:0},onIconClass:{type:String,default:""},offIconClass:{type:String,default:""},onText:{type:String,default:"ON"},offText:{type:String,default:"OFF"},onColor:{type:String,default:""},offColor:{type:String,default:""},onValue:{type:[Boolean,String,Number],default:!0},offValue:{type:[Boolean,String,Number],default:!1},name:{type:String,default:""},allowFocus:{type:Boolean,default:!1}},data:function(){return{coreWidth:this.width}},created:function(){~[this.onValue,this.offValue].indexOf(this.value)||this.$emit("input",this.offValue)},computed:{checked:function(){return this.value===this.onValue},hasText:function(){return this.onText||this.offText},transform:function(){return this.checked?"translate("+(this.coreWidth-20)+"px, 2px)":"translate(2px, 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t=this;e?(this.handleIconShow(),this.broadcast("ElSelectDropdown","updatePopper"),this.filterable&&(this.query=this.selectedLabel,this.multiple?this.$refs.input.focus():(this.remote||(this.broadcast("ElOption","queryChange",""),this.broadcast("ElOptionGroup","queryChange")),this.broadcast("ElInput","inputSelect")))):(this.$refs.reference.$el.querySelector("input").blur(),this.handleIconHide(),this.broadcast("ElSelectDropdown","destroyPopper"),this.$refs.input&&this.$refs.input.blur(),this.query="",this.selectedLabel="",this.inputLength=20,this.resetHoverIndex(),this.$nextTick(function(){t.$refs.input&&""===t.$refs.input.value&&0===t.selected.length&&(t.currentPlaceholder=t.cachedPlaceHolder)}),this.multiple||this.selected&&(this.filterable&&this.allowCreate&&this.createdSelected&&this.createdOption?this.selectedLabel=this.createdLabel:this.selectedLabel=this.selected.currentLabel,this.filterable&&(this.query=this.selectedLabel))),this.$emit("visible-change",e)},options:function(e){if(!this.$isServer){this.optionsAllDisabled=e.length===e.filter(function(e){return 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e=this.maxHeight?{bottom:this.layout.scrollX&&this.data.length?this.layout.gutterWidth+"px":""}:{height:this.layout.viewportHeight?this.layout.viewportHeight+"px":""}}},watch:{height:function(e){this.layout.setHeight(e)},currentRowKey:function(e){this.store.setCurrentRowKey(e)},data:{immediate:!0,handler:function(e){this.store.commit("setData",e),this.$ready&&this.doLayout()}},expandRowKeys:function(e){this.store.setExpandRowKeys(e)}},destroyed:function(){this.windowResizeListener&&(0,u.removeResizeListener)(this.$el,this.windowResizeListener)},mounted:function(){var e=this;this.bindEvents(),this.doLayout(),this.store.states.columns.forEach(function(t){t.filteredValue&&t.filteredValue.length&&e.store.commit("filterChange",{column:t,values:t.filteredValue,silent:!0})}),this.$ready=!0},data:function(){var e=new p.default(this,{rowKey:this.rowKey,defaultExpandAll:this.defaultExpandAll}),t=new v.default({store:e,table:this,fit:this.fit,showHeader:this.showHeader});return{store:e,layout:t,isHidden:!1,renderExpanded:null,resizeProxyVisible:!1}}}},function(e,t){e.exports=i(162)},function(e,t){e.exports=i(156)},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(133),r=n(a),s=i(69),o=n(s),l=i(134),c=function(e,t){var i=t.sortingColumn;return i&&"string"!=typeof i.sortable?(0,l.orderBy)(e,t.sortProp,t.sortOrder,i.sortMethod):e},u=function(e,t){var i={};return(e||[]).forEach(function(e,n){i[(0,l.getRowIdentity)(e,t)]={row:e,index:n}}),i},d=function(e,t,i){var n=!1,a=e.selection,r=a.indexOf(t);return"undefined"==typeof i?r===-1?(a.push(t),n=!0):(a.splice(r,1),n=!0):i&&r===-1?(a.push(t),n=!0):!i&&r>-1&&(a.splice(r,1),n=!0),n},h=function(e){var t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:{};if(!e)throw new Error("Table is required.");this.table=e,this.states={rowKey:null,_columns:[],originColumns:[],columns:[],fixedColumns:[],rightFixedColumns:[],isComplex:!1,_data:null,filteredData:null,data:null,sortingColumn:null,sortProp:null,sortOrder:null,isAllSelected:!1,selection:[],reserveSelection:!1,selectable:null,currentRow:null,hoverRow:null,filters:{},expandRows:[],defaultExpandAll:!1};for(var i in t)t.hasOwnProperty(i)&&this.states.hasOwnProperty(i)&&(this.states[i]=t[i])};h.prototype.mutations={setData:function(e,t){var i=this,n=e._data!==t;e._data=t,e.data=c(t||[],e),this.updateCurrentRow(),e.reserveSelection?!function(){var t=e.rowKey;t?!function(){var n=e.selection,a=u(n,t);e.data.forEach(function(e){var i=(0,l.getRowIdentity)(e,t),r=a[i];r&&(n[r.index]=e)}),i.updateAllSelected()}():console.warn("WARN: rowKey is required when reserve-selection is enabled.")}():(n?this.clearSelection():this.cleanSelection(),this.updateAllSelected());var a=e.defaultExpandAll;a&&(this.states.expandRows=(e.data||[]).slice(0)),r.default.nextTick(function(){return i.table.updateScrollY()})},changeSortCondition:function(e){var t=this;e.data=c(e.filteredData||e._data||[],e),this.table.$emit("sort-change",{column:this.states.sortingColumn,prop:this.states.sortProp,order:this.states.sortOrder}),r.default.nextTick(function(){return t.table.updateScrollY()})},filterChange:function(e,t){var i=this,n=t.column,a=t.values,s=t.silent;a&&!Array.isArray(a)&&(a=[a]);var o=n.property,u={};o&&(e.filters[n.id]=a,u[n.columnKey||n.id]=a);var d=e._data;Object.keys(e.filters).forEach(function(t){var n=e.filters[t];if(n&&0!==n.length){var a=(0,l.getColumnById)(i.states,t);a&&a.filterMethod&&(d=d.filter(function(e){return n.some(function(t){return a.filterMethod.call(null,t,e)})}))}}),e.filteredData=d,e.data=c(d,e),s||this.table.$emit("filter-change",u),r.default.nextTick(function(){return i.table.updateScrollY()})},insertColumn:function(e,t,i,n){var a=e._columns;n&&(a=n.children,a||(a=n.children=[])),"undefined"!=typeof i?a.splice(i,0,t):a.push(t),"selection"===t.type&&(e.selectable=t.selectable,e.reserveSelection=t.reserveSelection),this.updateColumns(),this.scheduleLayout()},removeColumn:function(e,t){var i=e._columns;i&&i.splice(i.indexOf(t),1),this.updateColumns(),this.scheduleLayout()},setHoverRow:function(e,t){e.hoverRow=t},setCurrentRow:function(e,t){var i=e.currentRow;e.currentRow=t,i!==t&&this.table.$emit("current-change",t,i)},rowSelectedChanged:function(e,t){var i=d(e,t),n=e.selection;if(i){var a=this.table;a.$emit("selection-change",n),a.$emit("select",n,t)}this.updateAllSelected()},toggleRowExpanded:function(e,t,i){var n=e.expandRows;if("undefined"!=typeof i){var a=n.indexOf(t);i?a===-1&&n.push(t):a!==-1&&n.splice(a,1)}else{var r=n.indexOf(t);r===-1?n.push(t):n.splice(r,1)}this.table.$emit("expand",t,n.indexOf(t)!==-1)},toggleAllSelection:(0,o.default)(10,function(e){var t=e.data||[],i=!e.isAllSelected,n=this.states.selection,a=!1;t.forEach(function(t,n){e.selectable?e.selectable.call(null,t,n)&&d(e,t,i)&&(a=!0):d(e,t,i)&&(a=!0)});var r=this.table;a&&r.$emit("selection-change",n),r.$emit("select-all",n),e.isAllSelected=i})};var f=function e(t){var i=[];return t.forEach(function(t){t.children?i.push.apply(i,e(t.children)):i.push(t)}),i};h.prototype.updateColumns=function(){var e=this.states,t=e._columns||[];e.fixedColumns=t.filter(function(e){return e.fixed===!0||"left"===e.fixed}),e.rightFixedColumns=t.filter(function(e){return"right"===e.fixed}),e.fixedColumns.length>0&&t[0]&&"selection"===t[0].type&&!t[0].fixed&&(t[0].fixed=!0,e.fixedColumns.unshift(t[0])),e.originColumns=[].concat(e.fixedColumns).concat(t.filter(function(e){return!e.fixed})).concat(e.rightFixedColumns),e.columns=f(e.originColumns),e.isComplex=e.fixedColumns.length>0||e.rightFixedColumns.length>0},h.prototype.isSelected=function(e){return(this.states.selection||[]).indexOf(e)>-1},h.prototype.clearSelection=function(){var e=this.states;e.isAllSelected=!1;var t=e.selection;e.selection=[],t.length>0&&this.table.$emit("selection-change",e.selection)},h.prototype.setExpandRowKeys=function(e){var t=[],i=this.states.data,n=this.states.rowKey;if(!n)throw new Error("[Table] prop row-key should not be empty.");var a=u(i,n);e.forEach(function(e){var i=a[e];i&&t.push(i.row)}),this.states.expandRows=t},h.prototype.toggleRowSelection=function(e,t){var i=d(this.states,e,t);i&&this.table.$emit("selection-change",this.states.selection)},h.prototype.cleanSelection=function(){var e=this.states.selection||[],t=this.states.data,i=this.states.rowKey,n=void 0;if(i){n=[];var a=u(e,i),r=u(t,i);for(var s in a)a.hasOwnProperty(s)&&!r[s]&&n.push(a[s].row)}else n=e.filter(function(e){return t.indexOf(e)===-1});n.forEach(function(t){e.splice(e.indexOf(t),1)}),n.length&&this.table.$emit("selection-change",e)},h.prototype.updateAllSelected=function(){var e=this.states,t=e.selection,i=e.rowKey,n=e.selectable,a=e.data;if(!a||0===a.length)return void(e.isAllSelected=!1);var r=void 0;i&&(r=u(e.selection,i));for(var s=function(e){return r?!!r[(0,l.getRowIdentity)(e,i)]:t.indexOf(e)!==-1},o=!0,c=0,d=0,h=a.length;d<h;d++){var f=a[d];if(n){var p=n.call(null,f,d);if(p){if(!s(f)){o=!1;break}c++}}else{if(!s(f)){o=!1;break}c++}}0===c&&(o=!1),e.isAllSelected=o},h.prototype.scheduleLayout=function(){this.table.debouncedLayout()},h.prototype.setCurrentRowKey=function(e){var t=this.states,i=t.rowKey;if(!i)throw new Error("[Table] row-key should not be empty.");var n=t.data||[],a=u(n,i),r=a[e];r&&(t.currentRow=r.row)},h.prototype.updateCurrentRow=function(){var e=this.states,t=this.table,i=e.data||[],n=e.currentRow;i.indexOf(n)===-1&&(e.currentRow=null,e.currentRow!==n&&t.$emit("current-change",null,n))},h.prototype.commit=function(e){var t=this.mutations;if(!t[e])throw new Error("Action not found: "+e);for(var i=arguments.length,n=Array(i>1?i-1:0),a=1;a<i;a++)n[a-1]=arguments[a];t[e].apply(this,[this.states].concat(n))},t.default=h},function(e,t){e.exports=i(2)},function(e,t,i){"use strict";t.__esModule=!0,t.getRowIdentity=t.mousewheel=t.getColumnByCell=t.getColumnById=t.orderBy=t.getCell=void 0;var n="function"==typeof Symbol&&"symbol"==typeof Symbol.iterator?function(e){return typeof e}:function(e){return e&&"function"==typeof Symbol&&e.constructor===Symbol&&e!==Symbol.prototype?"symbol":typeof e},a=i(107),r=(t.getCell=function(e){for(var t=e.target;t&&"HTML"!==t.tagName.toUpperCase();){if("TD"===t.tagName.toUpperCase())return t;t=t.parentNode}return null},function(e){return null!==e&&"object"===("undefined"==typeof e?"undefined":n(e))}),s=(t.orderBy=function(e,t,i,n){if("string"==typeof i&&(i="descending"===i?-1:1),!t&&!n)return e;var s=i&&i<0?-1:1;return e.slice().sort(n?function(e,t){return n(e,t)?s:-s}:function(e,i){return"$key"!==t&&(r(e)&&"$value"in e&&(e=e.$value),r(i)&&"$value"in i&&(i=i.$value)),e=r(e)?(0,a.getValueByPath)(e,t):e,i=r(i)?(0,a.getValueByPath)(i,t):i,e===i?0:e>i?s:-s})},t.getColumnById=function(e,t){var i=null;return e.columns.forEach(function(e){e.id===t&&(i=e)}),i}),o=(t.getColumnByCell=function(e,t){var i=(t.className||"").match(/el-table_[^\s]+/gm);return i?s(e,i[0]):null},"undefined"!=typeof navigator&&navigator.userAgent.toLowerCase().indexOf("firefox")>-1);t.mousewheel=function(e,t){e&&e.addEventListener&&e.addEventListener(o?"DOMMouseScroll":"mousewheel",t)},t.getRowIdentity=function(e,t){if(!e)throw new Error("row is required when get row identity");if("string"==typeof t){if(t.indexOf(".")<0)return e[t];for(var i=t.split("."),n=e,a=0;a<i.length;a++)n=n[i[a]];return n}if("function"==typeof t)return t.call(null,e)}},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}function a(e,t){if(!(e instanceof t))throw new TypeError("Cannot call a class as a function")}t.__esModule=!0;var r=i(136),s=n(r),o=function(){function e(t){a(this,e),this.table=null,this.store=null,this.columns=null,this.fit=!0,this.showHeader=!0,this.height=null,this.scrollX=!1,this.scrollY=!1,this.bodyWidth=null,this.fixedWidth=null,this.rightFixedWidth=null,this.tableHeight=null,this.headerHeight=44,this.footerHeight=44,this.viewportHeight=null,this.bodyHeight=null,this.fixedBodyHeight=null,this.gutterWidth=(0,s.default)();for(var i in t)t.hasOwnProperty(i)&&(this[i]=t[i]);if(!this.table)throw new Error("table is required for Table Layout");if(!this.store)throw new Error("store is required for Table Layout")}return e.prototype.updateScrollY=function(){var e=this.height;if("string"==typeof e||"number"==typeof e){var t=this.table.bodyWrapper;if(this.table.$el&&t){var i=t.querySelector(".el-table__body");this.scrollY=i.offsetHeight>t.offsetHeight}}},e.prototype.setHeight=function(e){var t=arguments.length>1&&void 0!==arguments[1]?arguments[1]:"height",i=this.table.$el;"string"==typeof e&&/^\d+$/.test(e)&&(e=Number(e)),this.height=e,i&&("number"==typeof e?(i.style[t]=e+"px",this.updateHeight()):"string"==typeof e&&(""===e&&(i.style[t]=""),this.updateHeight()))},e.prototype.setMaxHeight=function(e){return this.setHeight(e,"max-height")},e.prototype.updateHeight=function(){var e=this.tableHeight=this.table.$el.clientHeight,t=!this.table.data||0===this.table.data.length,i=this.table.$refs,n=i.headerWrapper,a=i.footerWrapper,r=this.footerHeight=a?a.offsetHeight:0;if(!this.showHeader||n){if(this.showHeader){var s=this.headerHeight=n.offsetHeight,o=e-s-r+(a?1:0);null===this.height||isNaN(this.height)&&"string"!=typeof this.height||(this.bodyHeight=o),this.fixedBodyHeight=this.scrollX?o-this.gutterWidth:o}else this.headerHeight=0,null===this.height||isNaN(this.height)&&"string"!=typeof this.height||(this.bodyHeight=e-r+(a?1:0)),this.fixedBodyHeight=this.scrollX?e-this.gutterWidth:e;this.viewportHeight=this.scrollX?e-(t?0:this.gutterWidth):e}},e.prototype.update=function(){var e=this.fit,t=this.table.columns,i=this.table.$el.clientWidth,n=0,a=[];t.forEach(function(e){e.isColumnGroup?a.push.apply(a,e.columns):a.push(e)});var r=a.filter(function(e){return"number"!=typeof e.width});if(r.length>0&&e){if(a.forEach(function(e){n+=e.width||e.minWidth||80}),n<i-this.gutterWidth){this.scrollX=!1;var s=i-this.gutterWidth-n;1===r.length?r[0].realWidth=(r[0].minWidth||80)+s:!function(){var e=r.reduce(function(e,t){return e+(t.minWidth||80)},0),t=s/e,i=0;r.forEach(function(e,n){if(0!==n){var a=Math.floor((e.minWidth||80)*t);i+=a,e.realWidth=(e.minWidth||80)+a}}),r[0].realWidth=(r[0].minWidth||80)+s-i}()}else this.scrollX=!0,r.forEach(function(e){e.realWidth=e.minWidth});this.bodyWidth=Math.max(n,i)}else a.forEach(function(e){e.width||e.minWidth?e.realWidth=e.width||e.minWidth:e.realWidth=80,n+=e.realWidth}),this.scrollX=n>i,this.bodyWidth=n;var o=this.store.states.fixedColumns;if(o.length>0){var l=0;o.forEach(function(e){l+=e.realWidth}),this.fixedWidth=l}var c=this.store.states.rightFixedColumns;if(c.length>0){var u=0;c.forEach(function(e){u+=e.realWidth}),this.rightFixedWidth=u}},e}();t.default=o},function(e,t){e.exports=i(144)},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(134),r=i(44),s=i(130),o=n(s),l=i(138),c=n(l),u=i(69),d=n(u);t.default={components:{ElCheckbox:o.default,ElTooltip:c.default},props:{store:{required:!0},stripe:Boolean,context:{},layout:{required:!0},rowClassName:[String,Function],rowStyle:[Object,Function],fixed:String,highlight:Boolean},render:function(e){var t=this,i=this.columns.map(function(e,i){return t.isColumnHidden(i)});return e("table",{class:"el-table__body",attrs:{cellspacing:"0",cellpadding:"0",border:"0"}},[e("colgroup",null,[this._l(this.columns,function(t){return e("col",{attrs:{name:t.id,width:t.realWidth||t.width}},[])})]),e("tbody",null,[this._l(this.data,function(n,a){return[e("tr",{style:t.rowStyle?t.getRowStyle(n,a):null,key:t.table.rowKey?t.getKeyOfRow(n,a):a,on:{dblclick:function(e){return t.handleDoubleClick(e,n)},click:function(e){return t.handleClick(e,n)},contextmenu:function(e){return t.handleContextMenu(e,n)},mouseenter:function(e){return t.handleMouseEnter(a)},mouseleave:function(e){return t.handleMouseLeave()}},class:[t.getRowClass(n,a)]},[t._l(t.columns,function(r,s){return e("td",{class:[r.id,r.align,r.className||"",i[s]?"is-hidden":""],on:{mouseenter:function(e){return t.handleCellMouseEnter(e,n)},mouseleave:t.handleCellMouseLeave}},[r.renderCell.call(t._renderProxy,e,{row:n,column:r,$index:a,store:t.store,_self:t.context||t.table.$vnode.context},i[s])])}),!t.fixed&&t.layout.scrollY&&t.layout.gutterWidth?e("td",{class:"gutter"},[]):""]),t.store.states.expandRows.indexOf(n)>-1?e("tr",null,[e("td",{attrs:{colspan:t.columns.length},class:"el-table__expanded-cell"},[t.table.renderExpanded?t.table.renderExpanded(e,{row:n,$index:a,store:t.store}):""])]):""]}).concat(this._self.$parent.$slots.append).concat(e("el-tooltip",{attrs:{effect:this.table.tooltipEffect,placement:"top",content:this.tooltipContent},ref:"tooltip"},[]))])])},watch:{"store.states.hoverRow":function(e,t){if(this.store.states.isComplex){var i=this.$el;if(i){var n=i.querySelectorAll("tbody > tr.el-table__row"),a=n[t],s=n[e];a&&(0,r.removeClass)(a,"hover-row"),s&&(0,r.addClass)(s,"hover-row")}}},"store.states.currentRow":function(e,t){if(this.highlight){var i=this.$el;if(i){var n=this.store.states.data,a=i.querySelectorAll("tbody > tr.el-table__row"),s=a[n.indexOf(t)],o=a[n.indexOf(e)];s?(0,r.removeClass)(s,"current-row"):a&&[].forEach.call(a,function(e){return(0,r.removeClass)(e,"current-row")}),o&&(0,r.addClass)(o,"current-row")}}}},computed:{table:function(){return this.$parent},data:function(){return this.store.states.data},columnsCount:function(){return this.store.states.columns.length},leftFixedCount:function(){return this.store.states.fixedColumns.length},rightFixedCount:function(){return this.store.states.rightFixedColumns.length},columns:function(){return this.store.states.columns}},data:function(){return{tooltipContent:""}},created:function(){this.activateTooltip=(0,d.default)(50,function(e){return e.handleShowPopper(); })},methods:{getKeyOfRow:function(e,t){var i=this.table.rowKey;return i?(0,a.getRowIdentity)(e,i):t},isColumnHidden:function(e){return this.fixed===!0||"left"===this.fixed?e>=this.leftFixedCount:"right"===this.fixed?e<this.columnsCount-this.rightFixedCount:e<this.leftFixedCount||e>=this.columnsCount-this.rightFixedCount},getRowStyle:function(e,t){var i=this.rowStyle;return"function"==typeof i?i.call(null,e,t):i},getRowClass:function(e,t){var i=["el-table__row"];this.stripe&&t%2===1&&i.push("el-table__row--striped");var n=this.rowClassName;return"string"==typeof n?i.push(n):"function"==typeof n&&i.push(n.call(null,e,t)||""),i.join(" ")},handleCellMouseEnter:function(e,t){var i=this.table,n=(0,a.getCell)(e);if(n){var s=(0,a.getColumnByCell)(i,n),o=i.hoverState={cell:n,column:s,row:t};i.$emit("cell-mouse-enter",o.row,o.column,o.cell,e)}var l=e.target.querySelector(".cell");if((0,r.hasClass)(l,"el-tooltip")&&l.scrollWidth>l.offsetWidth){var c=this.$refs.tooltip;this.tooltipContent=n.innerText,c.referenceElm=n,c.$refs.popper&&(c.$refs.popper.style.display="none"),c.doDestroy(),c.setExpectedState(!0),this.activateTooltip(c)}},handleCellMouseLeave:function(e){var t=this.$refs.tooltip;t&&(t.setExpectedState(!1),t.handleClosePopper());var i=(0,a.getCell)(e);if(i){var n=this.table.hoverState;this.table.$emit("cell-mouse-leave",n.row,n.column,n.cell,e)}},handleMouseEnter:function(e){this.store.commit("setHoverRow",e)},handleMouseLeave:function(){this.store.commit("setHoverRow",null)},handleContextMenu:function(e,t){this.handleEvent(e,t,"contextmenu")},handleDoubleClick:function(e,t){this.handleEvent(e,t,"dblclick")},handleClick:function(e,t){this.store.commit("setCurrentRow",t),this.handleEvent(e,t,"click")},handleEvent:function(e,t,i){var n=this.table,r=(0,a.getCell)(e),s=void 0;r&&(s=(0,a.getColumnByCell)(n,r),s&&n.$emit("cell-"+i,t,s,r,e)),n.$emit("row-"+i,t,e,s)},handleExpandClick:function(e){this.store.commit("toggleRowExpanded",e)}}}},function(e,t){e.exports=i(163)},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(44),r=i(130),s=n(r),o=i(109),l=n(o),c=i(133),u=n(c),d=i(140),h=n(d),f=function e(t){var i=[];return t.forEach(function(t){t.children?(i.push(t),i.push.apply(i,e(t.children))):i.push(t)}),i},p=function(e){var t=1,i=function e(i,n){if(n&&(i.level=n.level+1,t<i.level&&(t=i.level)),i.children){var a=0;i.children.forEach(function(t){e(t,i),a+=t.colSpan}),i.colSpan=a}else i.colSpan=1};e.forEach(function(e){e.level=1,i(e)});for(var n=[],a=0;a<t;a++)n.push([]);var r=f(e);return r.forEach(function(e){e.children?e.rowSpan=1:e.rowSpan=t-e.level+1,n[e.level-1].push(e)}),n};t.default={name:"ElTableHeader",render:function(e){var t=this,i=this.store.states.originColumns,n=p(i,this.columns);return e("table",{class:"el-table__header",attrs:{cellspacing:"0",cellpadding:"0",border:"0"}},[e("colgroup",null,[this._l(this.columns,function(t){return e("col",{attrs:{name:t.id,width:t.realWidth||t.width}},[])}),!this.fixed&&this.layout.gutterWidth?e("col",{attrs:{name:"gutter",width:this.layout.scrollY?this.layout.gutterWidth:""}},[]):""]),e("thead",null,[this._l(n,function(i,n){return e("tr",null,[t._l(i,function(a,r){return e("th",{attrs:{colspan:a.colSpan,rowspan:a.rowSpan},on:{mousemove:function(e){return t.handleMouseMove(e,a)},mouseout:t.handleMouseOut,mousedown:function(e){return t.handleMouseDown(e,a)},click:function(e){return 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t.handleFilterClick(e,a)}}},[e("i",{class:["el-icon-arrow-down",a.filterOpened?"el-icon-arrow-up":""]},[])]):""])])}),!t.fixed&&t.layout.gutterWidth?e("th",{class:"gutter",style:{width:t.layout.scrollY?t.layout.gutterWidth+"px":"0"}},[]):""])})])])},props:{fixed:String,store:{required:!0},layout:{required:!0},border:Boolean,defaultSort:{type:Object,default:function(){return{prop:"",order:""}}}},components:{ElCheckbox:s.default,ElTag:l.default},computed:{isAllSelected:function(){return this.store.states.isAllSelected},columnsCount:function(){return this.store.states.columns.length},leftFixedCount:function(){return this.store.states.fixedColumns.length},rightFixedCount:function(){return this.store.states.rightFixedColumns.length},columns:function(){return this.store.states.columns}},created:function(){this.filterPanels={}},mounted:function(){var e=this;this.defaultSort.prop&&!function(){var t=e.store.states;t.sortProp=e.defaultSort.prop,t.sortOrder=e.defaultSort.order||"ascending",e.$nextTick(function(i){for(var n=0,a=e.columns.length;n<a;n++){var r=e.columns[n];if(r.property===t.sortProp){r.order=t.sortOrder,t.sortingColumn=r;break}}t.sortingColumn&&e.store.commit("changeSortCondition")})}()},beforeDestroy:function(){var e=this.filterPanels;for(var t in e)e.hasOwnProperty(t)&&e[t]&&e[t].$destroy(!0)},methods:{isCellHidden:function(e,t){if(this.fixed===!0||"left"===this.fixed)return e>=this.leftFixedCount;if("right"===this.fixed){for(var i=0,n=0;n<e;n++)i+=t[n].colSpan;return i<this.columnsCount-this.rightFixedCount}return e<this.leftFixedCount||e>=this.columnsCount-this.rightFixedCount},toggleAllSelection:function(){this.store.commit("toggleAllSelection")},handleFilterClick:function(e,t){e.stopPropagation();var i=e.target,n=i.parentNode,a=this.$parent,r=this.filterPanels[t.id];return r&&t.filterOpened?void(r.showPopper=!1):(r||(r=new 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u=n.$refs.resizeProxy;u.style.left=i.dragState.startLeft+"px",document.onselectstart=function(){return!1},document.ondragstart=function(){return!1};var d=function(e){var t=e.clientX-i.dragState.startMouseLeft,n=i.dragState.startLeft+t;u.style.left=Math.max(c,n)+"px"},h=function r(){if(i.dragging){var s=i.dragState,l=s.startColumnLeft,c=s.startLeft,h=parseInt(u.style.left,10),f=h-l;t.width=t.realWidth=f,n.$emit("header-dragend",t.width,c-l,t,e),i.store.scheduleLayout(),document.body.style.cursor="",i.dragging=!1,i.draggingColumn=null,i.dragState={},n.resizeProxyVisible=!1}document.removeEventListener("mousemove",d),document.removeEventListener("mouseup",r),document.onselectstart=null,document.ondragstart=null,setTimeout(function(){(0,a.removeClass)(o,"noclick")},0)};document.addEventListener("mousemove",d),document.addEventListener("mouseup",h)}()},handleMouseMove:function(e,t){if(!(t.children&&t.children.length>0)){for(var i=e.target;i&&"TH"!==i.tagName;)i=i.parentNode;if(t&&t.resizable&&!this.dragging&&this.border){var n=i.getBoundingClientRect(),r=document.body.style;n.width>12&&n.right-e.pageX<8?(r.cursor="col-resize",(0,a.hasClass)(i,"is-sortable")&&(i.style.cursor="col-resize"),this.draggingColumn=t):this.dragging||(r.cursor="",(0,a.hasClass)(i,"is-sortable")&&(i.style.cursor="pointer"),this.draggingColumn=null)}}},handleMouseOut:function(){this.$isServer||(document.body.style.cursor="")},toggleOrder:function(e){return e?"ascending"===e?"descending":null:"ascending"},handleSortClick:function(e,t,i){e.stopPropagation();for(var n=i||this.toggleOrder(t.order),r=e.target;r&&"TH"!==r.tagName;)r=r.parentNode;if(r&&"TH"===r.tagName&&(0,a.hasClass)(r,"noclick"))return void(0,a.removeClass)(r,"noclick");if(t.sortable){var s=this.store.states,o=s.sortProp,l=void 0,c=s.sortingColumn;c!==t&&(c&&(c.order=null),s.sortingColumn=t,o=t.property),n?l=t.order=n:(l=t.order=null,s.sortingColumn=null,o=null),s.sortProp=o,s.sortOrder=l,this.store.commit("changeSortCondition")}}},data:function(){return{draggingColumn:null,dragging:!1,dragState:{}}}}},function(e,t,i){var n=i(5)(i(141),i(144),null,null,null);e.exports=n.exports},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(24),r=n(a),s=i(14),o=i(10),l=n(o),c=i(21),u=n(c),d=i(142),h=n(d),f=i(130),p=n(f),m=i(143),v=n(m);t.default={name:"ElTableFilterPanel",mixins:[r.default,l.default],directives:{Clickoutside:u.default},components:{ElCheckbox:p.default,ElCheckboxGroup:v.default},props:{placement:{type:String,default:"bottom-end"}},customRender:function(e){return e("div",{class:"el-table-filter"},[e("div",{class:"el-table-filter__content"},[]),e("div",{class:"el-table-filter__bottom"},[e("button",{on:{click:this.handleConfirm}},[this.t("el.table.confirmFilter")]),e("button",{on:{click:this.handleReset}},[this.t("el.table.resetFilter")])])])},methods:{isActive:function(e){return e.value===this.filterValue},handleOutsideClick:function(){this.showPopper=!1},handleConfirm:function(){this.confirmFilter(this.filteredValue),this.handleOutsideClick()},handleReset:function(){this.filteredValue=[],this.confirmFilter(this.filteredValue),this.handleOutsideClick()},handleSelect:function(e){this.filterValue=e,"undefined"!=typeof e&&null!==e?this.confirmFilter(this.filteredValue):this.confirmFilter([]),this.handleOutsideClick()},confirmFilter:function(e){this.table.store.commit("filterChange",{column:this.column,values:e})}},data:function(){return{table:null,cell:null,column:null}},computed:{filters:function(){return 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0"}],ref:"footerWrapper",staticClass:"el-table__footer-wrapper"},[i("table-footer",{style:{width:e.layout.bodyWidth?e.layout.bodyWidth+"px":""},attrs:{store:e.store,layout:e.layout,border:e.border,"sum-text":e.sumText||e.t("el.table.sumText"),"summary-method":e.summaryMethod,"default-sort":e.defaultSort}})],1):e._e(),e.fixedColumns.length>0?i("div",{ref:"fixedWrapper",staticClass:"el-table__fixed",style:[{width:e.layout.fixedWidth?e.layout.fixedWidth+"px":""},e.fixedHeight]},[e.showHeader?i("div",{ref:"fixedHeaderWrapper",staticClass:"el-table__fixed-header-wrapper"},[i("table-header",{style:{width:e.layout.fixedWidth?e.layout.fixedWidth+"px":""},attrs:{fixed:"left",border:e.border,store:e.store,layout:e.layout}})],1):e._e(),i("div",{ref:"fixedBodyWrapper",staticClass:"el-table__fixed-body-wrapper",style:[{top:e.layout.headerHeight+"px"},e.fixedBodyHeight]},[i("table-body",{style:{width:e.layout.fixedWidth?e.layout.fixedWidth+"px":""},attrs:{fixed:"left",store:e.store,stripe:e.stripe,layout:e.layout,highlight:e.highlightCurrentRow,"row-class-name":e.rowClassName,"row-style":e.rowStyle}})],1),e.showSummary?i("div",{directives:[{name:"show",rawName:"v-show",value:e.data&&e.data.length>0,expression:"data && data.length > 0"}],ref:"fixedFooterWrapper",staticClass:"el-table__fixed-footer-wrapper"},[i("table-footer",{style:{width:e.layout.fixedWidth?e.layout.fixedWidth+"px":""},attrs:{fixed:"left",border:e.border,"sum-text":e.sumText||e.t("el.table.sumText"),"summary-method":e.summaryMethod,store:e.store,layout:e.layout}})],1):e._e()]):e._e(),e.rightFixedColumns.length>0?i("div",{ref:"rightFixedWrapper",staticClass:"el-table__fixed-right",style:[{width:e.layout.rightFixedWidth?e.layout.rightFixedWidth+"px":""},{right:e.layout.scrollY?(e.border?e.layout.gutterWidth:e.layout.gutterWidth||1)+"px":""},e.fixedHeight]},[e.showHeader?i("div",{ref:"rightFixedHeaderWrapper",staticClass:"el-table__fixed-header-wrapper"},[i("table-header",{style:{width:e.layout.rightFixedWidth?e.layout.rightFixedWidth+"px":""},attrs:{fixed:"right",border:e.border,store:e.store,layout:e.layout}})],1):e._e(),i("div",{ref:"rightFixedBodyWrapper",staticClass:"el-table__fixed-body-wrapper",style:[{top:e.layout.headerHeight+"px"},e.fixedBodyHeight]},[i("table-body",{style:{width:e.layout.rightFixedWidth?e.layout.rightFixedWidth+"px":""},attrs:{fixed:"right",store:e.store,stripe:e.stripe,layout:e.layout,"row-class-name":e.rowClassName,"row-style":e.rowStyle,highlight:e.highlightCurrentRow}})],1),e.showSummary?i("div",{directives:[{name:"show",rawName:"v-show",value:e.data&&e.data.length>0,expression:"data 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e&&e.__esModule?e:{default:e}}function a(e){if(null==e)throw new TypeError("Cannot destructure undefined")}t.__esModule=!0;var r=i(130),s=n(r),o=i(109),l=n(o),c=i(64),u=n(c),d=i(107),h=1,f={default:{order:""},selection:{width:48,minWidth:48,realWidth:48,order:"",className:"el-table-column--selection"},expand:{width:48,minWidth:48,realWidth:48,order:""},index:{width:48,minWidth:48,realWidth:48,order:""}},p={selection:{renderHeader:function(e){return e("el-checkbox",{nativeOn:{click:this.toggleAllSelection},attrs:{value:this.isAllSelected}},[])},renderCell:function(e,t){var i=t.row,n=t.column,a=t.store,r=t.$index;return e("el-checkbox",{attrs:{value:a.isSelected(i),disabled:!!n.selectable&&!n.selectable.call(null,i,r)},on:{input:function(){a.commit("rowSelectedChanged",i)}}},[])},sortable:!1,resizable:!1},index:{renderHeader:function(e,t){var i=t.column;return i.label||"#"},renderCell:function(e,t){var i=t.$index;return 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this.showTime},visibleTime:{get:function(){return(0,a.formatDate)(this.date,this.timeFormat)},set:function(e){if(e){var t=(0,a.parseDate)(e,this.timeFormat);t&&(t.setFullYear(this.date.getFullYear()),t.setMonth(this.date.getMonth()),t.setDate(this.date.getDate()),this.date=t,this.$refs.timepicker.value=t,this.timePickerVisible=!1)}}},visibleDate:{get:function(){return(0,a.formatDate)(this.date,this.dateFormat)},set:function(e){var t=(0,a.parseDate)(e,this.dateFormat);t&&("function"==typeof this.disabledDate&&this.disabledDate(t)||(t.setHours(this.date.getHours()),t.setMinutes(this.date.getMinutes()),t.setSeconds(this.date.getSeconds()),this.date=t,this.resetView()))}},yearLabel:function(){var e=this.year;if(!e)return"";var t=this.t("el.datepicker.year");if("year"===this.currentView){var i=10*Math.floor(e/10);return t?i+" "+t+" - "+(i+9)+" "+t:i+" - "+(i+9)}return this.year+" "+t},timeFormat:function(){return this.format&&this.format.indexOf("ss")===-1?"HH:mm":"HH:mm:ss"},dateFormat:function(){return this.format?this.format.replace("HH","").replace(":mm","").replace(":ss","").trim():"yyyy-MM-dd"}}}},function(e,t,i){var n=i(5)(i(159),i(163),null,null,null);e.exports=n.exports},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(153),r=i(10),s=n(r);t.default={mixins:[s.default],components:{TimeSpinner:i(160)},props:{pickerWidth:{},date:{default:function(){return new Date}},visible:Boolean},watch:{visible:function(e){this.currentVisible=e,e&&(this.oldHours=this.hours,this.oldMinutes=this.minutes,this.oldSeconds=this.seconds)},pickerWidth:function(e){this.width=e},value:function(e){var t=this,i=void 0;e instanceof Date?i=(0,a.limitRange)(e,this.selectableRange):e||(i=new Date),this.handleChange({hours:i.getHours(),minutes:i.getMinutes(),seconds:i.getSeconds()}),this.$nextTick(function(e){return t.ajustScrollTop()})},selectableRange:function(e){this.$refs.spinner.selectableRange=e}},data:function(){return{popperClass:"",format:"HH:mm:ss",value:"",hours:0,minutes:0,seconds:0,oldHours:0,oldMinutes:0,oldSeconds:0,selectableRange:[],currentDate:this.$options.defaultValue||this.date||new Date,currentVisible:this.visible||!1,width:this.pickerWidth||0}},computed:{showSeconds:function(){return(this.format||"").indexOf("ss")!==-1}},methods:{handleClear:function(){this.$emit("pick")},handleCancel:function(){this.currentDate.setHours(this.oldHours),this.currentDate.setMinutes(this.oldMinutes),this.currentDate.setSeconds(this.oldSeconds),this.hours=this.currentDate.getHours(),this.minutes=this.currentDate.getMinutes(),this.seconds=this.currentDate.getSeconds();var e=new Date((0,a.limitRange)(this.currentDate,this.selectableRange,"HH:mm:ss"));this.$emit("pick",e)},handleChange:function(e){void 0!==e.hours&&(this.currentDate.setHours(e.hours),this.hours=this.currentDate.getHours()),void 0!==e.minutes&&(this.currentDate.setMinutes(e.minutes),this.minutes=this.currentDate.getMinutes()),void 0!==e.seconds&&(this.currentDate.setSeconds(e.seconds),this.seconds=this.currentDate.getSeconds()),this.handleConfirm(!0)},setSelectionRange:function(e,t){this.$emit("select-range",e,t)},handleConfirm:function(){var e=arguments.length>0&&void 0!==arguments[0]&&arguments[0],t=arguments[1];if(!t){var i=new Date((0,a.limitRange)(this.currentDate,this.selectableRange,"HH:mm:ss"));this.$emit("pick",i,e,t)}},ajustScrollTop:function(){return this.$refs.spinner.ajustScrollTop()}},created:function(){this.hours=this.currentDate.getHours(),this.minutes=this.currentDate.getMinutes(),this.seconds=this.currentDate.getSeconds()},mounted:function(){var e=this;this.$nextTick(function(){return e.handleConfirm(!0,!0)}),this.$emit("mounted")}}},function(e,t,i){var n=i(5)(i(161),i(162),null,null,null);e.exports=n.exports},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(153),r=i(25),s=n(r),o=i(69),l=n(o);t.default={components:{ElScrollbar:s.default},props:{hours:{type:Number,default:0},minutes:{type:Number,default:0},seconds:{type:Number,default:0},showSeconds:{type:Boolean,default:!0}},watch:{hoursPrivate:function(e,t){e>=0&&e<=23||(this.hoursPrivate=t),this.ajustElTop("hour",e),this.$emit("change",{hours:e})},minutesPrivate:function(e,t){e>=0&&e<=59||(this.minutesPrivate=t),this.ajustElTop("minute",e),this.$emit("change",{minutes:e})},secondsPrivate:function(e,t){e>=0&&e<=59||(this.secondsPrivate=t),this.ajustElTop("second",e),this.$emit("change",{seconds:e})}},computed:{hoursList:function(){return(0,a.getRangeHours)(this.selectableRange)},hourEl:function(){return this.$refs.hour.wrap},minuteEl:function(){return this.$refs.minute.wrap},secondEl:function(){return this.$refs.second.wrap}},data:function(){return{hoursPrivate:0,minutesPrivate:0,secondsPrivate:0,selectableRange:[]}},created:function(){var e=this;this.debounceAjustElTop=(0,l.default)(100,function(t){return e.ajustElTop(t,e[t+"s"])})},mounted:function(){var e=this;this.$nextTick(function(){e.bindScrollEvent()})},methods:{handleClick:function(e,t,i){t.disabled||(this[e+"Private"]=t.value>=0?t.value:t,this.emitSelectRange(e))},emitSelectRange:function(e){"hours"===e?this.$emit("select-range",0,2):"minutes"===e?this.$emit("select-range",3,5):"seconds"===e&&this.$emit("select-range",6,8)},bindScrollEvent:function(){var e=this,t=function(t){e[t+"El"].onscroll=function(i){return e.handleScroll(t,i)}};t("hour"),t("minute"),t("second")},handleScroll:function(e){var t={};t[e+"s"]=Math.min(Math.floor((this[e+"El"].scrollTop-80)/32+3),""+e=="hour"?23:59),this.debounceAjustElTop(e),this.$emit("change",t)},ajustScrollTop:function(){this.ajustElTop("hour",this.hours),this.ajustElTop("minute",this.minutes),this.ajustElTop("second",this.seconds)},ajustElTop:function(e,t){this[e+"El"].scrollTop=Math.max(0,32*(t-2.5)+80)}}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"el-time-spinner",class:{"has-seconds":e.showSeconds}},[i("el-scrollbar",{ref:"hour",staticClass:"el-time-spinner__wrapper",attrs:{"wrap-style":"max-height: inherit;","view-class":"el-time-spinner__list",noresize:"",tag:"ul"},nativeOn:{mouseenter:function(t){e.emitSelectRange("hours")}}},e._l(e.hoursList,function(t,n){return i("li",{staticClass:"el-time-spinner__item",class:{active:n===e.hours,disabled:t},attrs:{"track-by":"hour"},domProps:{textContent:e._s(n)},on:{click:function(i){e.handleClick("hours",{value:n,disabled:t},!0)}}})})),i("el-scrollbar",{ref:"minute",staticClass:"el-time-spinner__wrapper",attrs:{"wrap-style":"max-height: inherit;","view-class":"el-time-spinner__list",noresize:"",tag:"ul"},nativeOn:{mouseenter:function(t){e.emitSelectRange("minutes")}}},e._l(60,function(t,n){return i("li",{staticClass:"el-time-spinner__item",class:{active:n===e.minutes},domProps:{textContent:e._s(n)},on:{click:function(t){e.handleClick("minutes",n,!0)}}})})),i("el-scrollbar",{directives:[{name:"show",rawName:"v-show",value:e.showSeconds,expression:"showSeconds"}],ref:"second",staticClass:"el-time-spinner__wrapper",attrs:{"wrap-style":"max-height: inherit;","view-class":"el-time-spinner__list",noresize:"",tag:"ul"},nativeOn:{mouseenter:function(t){e.emitSelectRange("seconds")}}},e._l(60,function(t,n){return i("li",{staticClass:"el-time-spinner__item",class:{active:n===e.seconds},domProps:{textContent:e._s(n)},on:{click:function(t){e.handleClick("seconds",n,!0)}}})}))],1)},staticRenderFns:[]}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("transition",{attrs:{name:"el-zoom-in-top"},on:{"after-leave":function(t){e.$emit("dodestroy")}}},[i("div",{directives:[{name:"show",rawName:"v-show",value:e.currentVisible,expression:"currentVisible"}],staticClass:"el-time-panel",class:e.popperClass,style:{width:e.width+"px"}},[i("div",{staticClass:"el-time-panel__content",class:{"has-seconds":e.showSeconds}},[i("time-spinner",{ref:"spinner",attrs:{"show-seconds":e.showSeconds,hours:e.hours,minutes:e.minutes,seconds:e.seconds},on:{change:e.handleChange,"select-range":e.setSelectionRange}})],1),i("div",{staticClass:"el-time-panel__footer"},[i("button",{staticClass:"el-time-panel__btn cancel",attrs:{type:"button"},on:{click:e.handleCancel}},[e._v(e._s(e.t("el.datepicker.cancel")))]),i("button",{staticClass:"el-time-panel__btn confirm",attrs:{type:"button"},on:{click:function(t){e.handleConfirm()}}},[e._v(e._s(e.t("el.datepicker.confirm")))])])])])},staticRenderFns:[]}},function(e,t,i){var n=i(5)(i(165),i(166),null,null,null);e.exports=n.exports},function(e,t,i){"use strict";t.__esModule=!0;var n=i(44);t.default={props:{disabledDate:{},date:{},year:{}},computed:{startYear:function(){return 10*Math.floor(this.year/10)}},methods:{getCellStyle:function(e){var t={},i=new Date(e,0,1,0),n=new Date(i);n.setFullYear(e+1);var a=!1;if("function"==typeof this.disabledDate){for(;i<n&&this.disabledDate(i);)i=new Date(i.getTime()+864e5);i-n===0&&(a=!0)}return t.disabled=a,t.current=Number(this.year)===e,t},nextTenYear:function(){this.$emit("pick",Number(this.year)+10,!1)},prevTenYear:function(){this.$emit("pick",Number(this.year)-10,!1)},handleYearTableClick:function(e){var t=e.target;if("A"===t.tagName){if((0,n.hasClass)(t.parentNode,"disabled"))return;var i=t.textContent||t.innerText;this.$emit("pick",Number(i))}}}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("table",{staticClass:"el-year-table",on:{click:e.handleYearTableClick}},[i("tbody",[i("tr",[i("td",{staticClass:"available",class:e.getCellStyle(e.startYear+0)},[i("a",{staticClass:"cell"},[e._v(e._s(e.startYear))])]),i("td",{staticClass:"available",class:e.getCellStyle(e.startYear+1)},[i("a",{staticClass:"cell"},[e._v(e._s(e.startYear+1))])]),i("td",{staticClass:"available",class:e.getCellStyle(e.startYear+2)},[i("a",{staticClass:"cell"},[e._v(e._s(e.startYear+2))])]),i("td",{staticClass:"available",class:e.getCellStyle(e.startYear+3)},[i("a",{staticClass:"cell"},[e._v(e._s(e.startYear+3))])])]),i("tr",[i("td",{staticClass:"available",class:e.getCellStyle(e.startYear+4)},[i("a",{staticClass:"cell"},[e._v(e._s(e.startYear+4))])]),i("td",{staticClass:"available",class:e.getCellStyle(e.startYear+5)},[i("a",{staticClass:"cell"},[e._v(e._s(e.startYear+5))])]),i("td",{staticClass:"available",class:e.getCellStyle(e.startYear+6)},[i("a",{staticClass:"cell"},[e._v(e._s(e.startYear+6))])]),i("td",{staticClass:"available",class:e.getCellStyle(e.startYear+7)},[i("a",{staticClass:"cell"},[e._v(e._s(e.startYear+7))])])]),i("tr",[i("td",{staticClass:"available",class:e.getCellStyle(e.startYear+8)},[i("a",{staticClass:"cell"},[e._v(e._s(e.startYear+8))])]),i("td",{staticClass:"available",class:e.getCellStyle(e.startYear+9)},[i("a",{staticClass:"cell"},[e._v(e._s(e.startYear+9))])]),i("td"),i("td")])])])},staticRenderFns:[]}},function(e,t,i){var n=i(5)(i(168),i(169),null,null,null);e.exports=n.exports},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(10),r=n(a),s=i(44);t.default={props:{disabledDate:{},date:{},month:{type:Number}},mixins:[r.default],methods:{getCellStyle:function(e){var t={},i=this.date.getFullYear(),n=new Date(0);n.setFullYear(i),n.setMonth(e,1),n.setHours(0);var a=new Date(n);a.setMonth(e+1);var r=!1;if("function"==typeof this.disabledDate)for(;n<a;){if(!this.disabledDate(n)){r=!1;break}n=new Date(n.getTime()+864e5),r=!0}return t.disabled=r,t.current=this.month===e,t},handleMonthTableClick:function(e){var t=e.target;if("A"===t.tagName&&!(0,s.hasClass)(t.parentNode,"disabled")){var i=t.parentNode.cellIndex,n=t.parentNode.parentNode.rowIndex,a=4*n+i;this.$emit("pick",a)}}}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("table",{staticClass:"el-month-table",on:{click:e.handleMonthTableClick}},[i("tbody",[i("tr",[i("td",{class:e.getCellStyle(0)},[i("a",{staticClass:"cell"},[e._v(e._s(e.t("el.datepicker.months.jan")))])]),i("td",{class:e.getCellStyle(1)},[i("a",{staticClass:"cell"},[e._v(e._s(e.t("el.datepicker.months.feb")))])]),i("td",{class:e.getCellStyle(2)},[i("a",{staticClass:"cell"},[e._v(e._s(e.t("el.datepicker.months.mar")))])]),i("td",{class:e.getCellStyle(3)},[i("a",{staticClass:"cell"},[e._v(e._s(e.t("el.datepicker.months.apr")))])])]),i("tr",[i("td",{class:e.getCellStyle(4)},[i("a",{staticClass:"cell"},[e._v(e._s(e.t("el.datepicker.months.may")))])]),i("td",{class:e.getCellStyle(5)},[i("a",{staticClass:"cell"},[e._v(e._s(e.t("el.datepicker.months.jun")))])]),i("td",{class:e.getCellStyle(6)},[i("a",{staticClass:"cell"},[e._v(e._s(e.t("el.datepicker.months.jul")))])]),i("td",{class:e.getCellStyle(7)},[i("a",{staticClass:"cell"},[e._v(e._s(e.t("el.datepicker.months.aug")))])])]),i("tr",[i("td",{class:e.getCellStyle(8)},[i("a",{staticClass:"cell"},[e._v(e._s(e.t("el.datepicker.months.sep")))])]),i("td",{class:e.getCellStyle(9)},[i("a",{staticClass:"cell"},[e._v(e._s(e.t("el.datepicker.months.oct")))])]),i("td",{class:e.getCellStyle(10)},[i("a",{staticClass:"cell"},[e._v(e._s(e.t("el.datepicker.months.nov")))])]),i("td",{class:e.getCellStyle(11)},[i("a",{staticClass:"cell"},[e._v(e._s(e.t("el.datepicker.months.dec")))])])])])])},staticRenderFns:[]}},function(e,t,i){var n=i(5)(i(171),i(172),null,null,null);e.exports=n.exports},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(153),r=i(44),s=i(10),o=n(s),l=["sun","mon","tue","wed","thu","fri","sat"],c=function(e){var t=new Date(e);return t.setHours(0,0,0,0),t.getTime()};t.default={mixins:[o.default],props:{firstDayOfWeek:{default:7,type:Number,validator:function(e){return e>=1&&e<=7}},date:{},year:{},month:{},week:{},selectionMode:{default:"day"},showWeekNumber:{type:Boolean,default:!1},disabledDate:{},minDate:{},maxDate:{},rangeState:{default:function(){return{endDate:null,selecting:!1,row:null,column:null}}}},computed:{offsetDay:function(){var e=this.firstDayOfWeek;return e>3?7-e:-e},WEEKS:function(){var e=this.firstDayOfWeek;return l.concat(l).slice(e,e+7)},monthDate:function(){return this.date.getDate()},startDate:function(){return(0,a.getStartDateOfMonth)(this.year,this.month)},rows:function e(){var t=new Date(this.year,this.month,1),i=(0,a.getFirstDayOfMonth)(t),n=(0,a.getDayCountOfMonth)(t.getFullYear(),t.getMonth()),r=(0,a.getDayCountOfMonth)(t.getFullYear(),0===t.getMonth()?11:t.getMonth()-1);i=0===i?7:i;for(var s=this.offsetDay,e=this.tableRows,o=1,l=void 0,u=this.startDate,d=this.disabledDate,h=c(new Date),f=0;f<6;f++){var p=e[f];this.showWeekNumber&&(p[0]||(p[0]={type:"week",text:(0,a.getWeekNumber)(new Date(u.getTime()+a.DAY_DURATION*(7*f+1)))}));for(var m=0;m<7;m++){var v=p[this.showWeekNumber?m+1:m];v||(v={row:f,column:m,type:"normal",inRange:!1,start:!1,end:!1}),v.type="normal";var g=7*f+m,y=u.getTime()+a.DAY_DURATION*(g-s);v.inRange=y>=c(this.minDate)&&y<=c(this.maxDate),v.start=this.minDate&&y===c(this.minDate),v.end=this.maxDate&&y===c(this.maxDate);var b=y===h;b&&(v.type="today"),f>=0&&f<=1?m+7*f>=i+s?(v.text=o++,2===o&&(l=7*f+m)):(v.text=r-(i+s-m%7)+1+7*f,v.type="prev-month"):o<=n?(v.text=o++,2===o&&(l=7*f+m)):(v.text=o++-n,v.type="next-month"),v.disabled="function"==typeof d&&d(new Date(y)),this.$set(p,this.showWeekNumber?m+1:m,v)}if("week"===this.selectionMode){var _=this.showWeekNumber?1:0,x=this.showWeekNumber?7:6,C=this.isWeekActive(p[_+1]);p[_].inRange=C,p[_].start=C,p[x].inRange=C,p[x].end=C}}return e.firstDayPosition=l,e}},watch:{"rangeState.endDate":function(e){this.markRange(e)},minDate:function(e,t){e&&!t?(this.rangeState.selecting=!0,this.markRange(e)):e?this.markRange():(this.rangeState.selecting=!1,this.markRange(e))},maxDate:function(e,t){e&&!t&&(this.rangeState.selecting=!1,this.markRange(e),this.$emit("pick",{minDate:this.minDate,maxDate:this.maxDate}))}},data:function(){return{tableRows:[[],[],[],[],[],[]]}},methods:{getCellClasses:function(e){var t=this.selectionMode,i=this.monthDate,n=[];return"normal"!==e.type&&"today"!==e.type||e.disabled?n.push(e.type):(n.push("available"),"today"===e.type&&n.push("today")),"day"!==t||"normal"!==e.type&&"today"!==e.type||Number(this.year)!==this.date.getFullYear()||this.month!==this.date.getMonth()||i!==Number(e.text)||n.push("current"),!e.inRange||"normal"!==e.type&&"today"!==e.type&&"week"!==this.selectionMode||(n.push("in-range"),e.start&&n.push("start-date"),e.end&&n.push("end-date")),e.disabled&&n.push("disabled"),n.join(" ")},getDateOfCell:function(e,t){var i=this.startDate;return new Date(i.getTime()+(7*e+(t-(this.showWeekNumber?1:0))-this.offsetDay)*a.DAY_DURATION)},getCellByDate:function(e){var t=this.startDate,i=this.rows,n=(e-t)/a.DAY_DURATION,r=i[Math.floor(n/7)];return this.showWeekNumber?r[n%7+1]:r[n%7]},isWeekActive:function(e){if("week"!==this.selectionMode)return!1;var t=new Date(this.year,this.month,1),i=t.getFullYear(),n=t.getMonth();return"prev-month"===e.type&&(t.setMonth(0===n?11:n-1),t.setFullYear(0===n?i-1:i)),"next-month"===e.type&&(t.setMonth(11===n?0:n+1),t.setFullYear(11===n?i+1:i)),t.setDate(parseInt(e.text,10)),(0,a.getWeekNumber)(t)===this.week},markRange:function(e){var t=this.startDate;e||(e=this.maxDate);for(var i=this.rows,n=this.minDate,r=0,s=i.length;r<s;r++)for(var o=i[r],l=0,u=o.length;l<u;l++)if(!this.showWeekNumber||0!==l){var d=o[l],h=7*r+l+(this.showWeekNumber?-1:0),f=t.getTime()+a.DAY_DURATION*(h-this.offsetDay);d.inRange=n&&f>=c(n)&&f<=c(e),d.start=n&&f===c(n.getTime()),d.end=e&&f===c(e.getTime())}},handleMouseMove:function(e){if(this.rangeState.selecting){this.$emit("changerange",{minDate:this.minDate,maxDate:this.maxDate,rangeState:this.rangeState});var t=e.target;if("TD"===t.tagName){var i=t.cellIndex,n=t.parentNode.rowIndex-1,a=this.rangeState,r=a.row,s=a.column;r===n&&s===i||(this.rangeState.row=n,this.rangeState.column=i,this.rangeState.endDate=this.getDateOfCell(n,i))}}},handleClick:function(e){var t=e.target;if("TD"===t.tagName&&!(0,r.hasClass)(t,"disabled")&&!(0,r.hasClass)(t,"week")){var i=this.selectionMode;"week"===i&&(t=t.parentNode.cells[1]);var n=Number(this.year),s=Number(this.month),o=t.cellIndex,l=t.parentNode.rowIndex,c=this.rows[l-1][o],u=c.text,d=t.className,h=new Date(n,s,1);if(d.indexOf("prev")!==-1?(0===s?(n-=1,s=11):s-=1,h.setFullYear(n),h.setMonth(s)):d.indexOf("next")!==-1&&(11===s?(n+=1,s=0):s+=1,h.setFullYear(n),h.setMonth(s)),h.setDate(parseInt(u,10)),"range"===this.selectionMode){if(this.minDate&&this.maxDate){var f=new Date(h.getTime()),p=null;this.$emit("pick",{minDate:f,maxDate:p},!1),this.rangeState.selecting=!0,this.markRange(this.minDate)}else if(this.minDate&&!this.maxDate)if(h>=this.minDate){var m=new Date(h.getTime());this.rangeState.selecting=!1,this.$emit("pick",{minDate:this.minDate,maxDate:m})}else{var v=new Date(h.getTime());this.$emit("pick",{minDate:v,maxDate:this.maxDate},!1)}else if(!this.minDate){var g=new Date(h.getTime());this.$emit("pick",{minDate:g,maxDate:this.maxDate},!1),this.rangeState.selecting=!0,this.markRange(this.minDate)}}else if("day"===i)this.$emit("pick",h);else if("week"===i){var y=(0,a.getWeekNumber)(h),b=h.getFullYear()+"w"+y;this.$emit("pick",{year:h.getFullYear(),week:y,value:b,date:h})}}}}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("table",{staticClass:"el-date-table",class:{"is-week-mode":"week"===e.selectionMode},attrs:{cellspacing:"0",cellpadding:"0"},on:{click:e.handleClick,mousemove:e.handleMouseMove}},[i("tbody",[i("tr",[e.showWeekNumber?i("th",[e._v(e._s(e.t("el.datepicker.week")))]):e._e(),e._l(e.WEEKS,function(t){return i("th",[e._v(e._s(e.t("el.datepicker.weeks."+t)))])})],2),e._l(e.rows,function(t){return i("tr",{staticClass:"el-date-table__row",class:{current:e.isWeekActive(t[1])}},e._l(t,function(t){return i("td",{class:e.getCellClasses(t),domProps:{textContent:e._s("today"===t.type?e.t("el.datepicker.today"):t.text)}})}))})],2)])},staticRenderFns:[]}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("transition",{attrs:{name:"el-zoom-in-top"},on:{"after-leave":function(t){e.$emit("dodestroy")}}},[i("div",{directives:[{name:"show",rawName:"v-show",value:e.visible,expression:"visible"}],staticClass:"el-picker-panel el-date-picker",class:[{"has-sidebar":e.$slots.sidebar||e.shortcuts,"has-time":e.showTime},e.popperClass],style:{width:e.width+"px"}},[i("div",{staticClass:"el-picker-panel__body-wrapper"},[e._t("sidebar"),e.shortcuts?i("div",{staticClass:"el-picker-panel__sidebar"},e._l(e.shortcuts,function(t){return 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mounted:function(t){e.$refs.timepicker.format=e.timeFormat}}})],1)]):e._e(),i("div",{directives:[{name:"show",rawName:"v-show",value:"time"!==e.currentView,expression:"currentView !== 'time'"}],staticClass:"el-date-picker__header"},[i("button",{staticClass:"el-picker-panel__icon-btn el-date-picker__prev-btn el-icon-d-arrow-left",attrs:{type:"button"},on:{click:e.prevYear}}),i("button",{directives:[{name:"show",rawName:"v-show",value:"date"===e.currentView,expression:"currentView === 'date'"}],staticClass:"el-picker-panel__icon-btn el-date-picker__prev-btn el-icon-arrow-left",attrs:{type:"button"},on:{click:e.prevMonth}}),i("span",{staticClass:"el-date-picker__header-label",on:{click:e.showYearPicker}},[e._v(e._s(e.yearLabel))]),i("span",{directives:[{name:"show",rawName:"v-show",value:"date"===e.currentView,expression:"currentView === 'date'"}],staticClass:"el-date-picker__header-label",class:{active:"month"===e.currentView},on:{click:e.showMonthPicker}},[e._v(e._s(e.t("el.datepicker.month"+(e.month+1))))]),i("button",{staticClass:"el-picker-panel__icon-btn el-date-picker__next-btn el-icon-d-arrow-right",attrs:{type:"button"},on:{click:e.nextYear}}),i("button",{directives:[{name:"show",rawName:"v-show",value:"date"===e.currentView,expression:"currentView === 'date'"}],staticClass:"el-picker-panel__icon-btn el-date-picker__next-btn el-icon-arrow-right",attrs:{type:"button"},on:{click:e.nextMonth}})]),i("div",{staticClass:"el-picker-panel__content"},[i("date-table",{directives:[{name:"show",rawName:"v-show",value:"date"===e.currentView,expression:"currentView === 'date'"}],attrs:{year:e.year,month:e.month,date:e.date,week:e.week,"selection-mode":e.selectionMode,"first-day-of-week":e.firstDayOfWeek,"disabled-date":e.disabledDate},on:{pick:e.handleDatePick}}),i("year-table",{directives:[{name:"show",rawName:"v-show",value:"year"===e.currentView,expression:"currentView === 'year'"}],ref:"yearTable",attrs:{year:e.year,date:e.date,"disabled-date":e.disabledDate},on:{pick:e.handleYearPick}}),i("month-table",{directives:[{name:"show",rawName:"v-show",value:"month"===e.currentView,expression:"currentView === 'month'"}],attrs:{month:e.month,date:e.date,"disabled-date":e.disabledDate},on:{pick:e.handleMonthPick}})],1)])],2),i("div",{directives:[{name:"show",rawName:"v-show",value:e.footerVisible&&"date"===e.currentView,expression:"footerVisible && currentView === 'date'"}],staticClass:"el-picker-panel__footer"},[i("a",{staticClass:"el-picker-panel__link-btn",attrs:{href:"JavaScript:"},on:{click:e.changeToNow}},[e._v(e._s(e.t("el.datepicker.now")))]),i("button",{staticClass:"el-picker-panel__btn",attrs:{type:"button"},on:{click:e.confirm}},[e._v(e._s(e.t("el.datepicker.confirm")))])])])])},staticRenderFns:[]}},function(e,t,i){var n=i(5)(i(175),i(176),null,null,null);e.exports=n.exports},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(153),r=i(10),s=n(r),o=i(158),l=n(o),c=i(170),u=n(c),d=i(20),h=n(d),f=function(e){return Array.isArray(e)?e[0]?new Date(e[0]):new Date:new Date(e)};t.default={mixins:[s.default],computed:{btnDisabled:function(){return!(this.minDate&&this.maxDate&&!this.selecting)},leftLabel:function(){return this.date.getFullYear()+" "+this.t("el.datepicker.year")+" "+this.t("el.datepicker.month"+(this.date.getMonth()+1))},rightLabel:function(){return this.rightDate.getFullYear()+" "+this.t("el.datepicker.year")+" "+this.t("el.datepicker.month"+(this.rightDate.getMonth()+1))},leftYear:function(){return this.date.getFullYear()},leftMonth:function(){return this.date.getMonth()},rightYear:function(){return this.rightDate.getFullYear()},rightMonth:function(){return this.rightDate.getMonth()},minVisibleDate:function(){return this.minDate?(0,a.formatDate)(this.minDate):""},maxVisibleDate:function(){return this.maxDate||this.minDate?(0,a.formatDate)(this.maxDate||this.minDate):""},minVisibleTime:function(){return this.minDate?(0,a.formatDate)(this.minDate,"HH:mm:ss"):""},maxVisibleTime:function(){return this.maxDate||this.minDate?(0,a.formatDate)(this.maxDate||this.minDate,"HH:mm:ss"):""},rightDate:function(){var e=new Date(this.date),t=e.getMonth();return e.setDate(1),11===t?(e.setFullYear(e.getFullYear()+1),e.setMonth(0)):e.setMonth(t+1),e}},data:function(){return{popperClass:"",minPickerWidth:0,maxPickerWidth:0,date:this.$options.defaultValue?f(this.$options.defaultValue):new Date,minDate:"",maxDate:"",rangeState:{endDate:null,selecting:!1,row:null,column:null},showTime:!1,shortcuts:"",value:"",visible:"",disabledDate:"",firstDayOfWeek:7,minTimePickerVisible:!1,maxTimePickerVisible:!1,width:0}},watch:{showTime:function(e){var t=this;e&&this.$nextTick(function(e){var i=t.$refs.minInput.$el,n=t.$refs.maxInput.$el;i&&(t.minPickerWidth=i.getBoundingClientRect().width+10),n&&(t.maxPickerWidth=n.getBoundingClientRect().width+10)})},minDate:function(){var e=this;this.$nextTick(function(){if(e.maxDate&&e.maxDate<e.minDate){var t="HH:mm:ss";e.$refs.maxTimePicker.selectableRange=(0,a.parseDate)((0,a.formatDate)(e.minDate,t),t),(0,a.parseDate)("23:59:59",t)}})},minTimePickerVisible:function(e){var t=this;e&&this.$nextTick(function(){return t.$refs.minTimePicker.ajustScrollTop()})},maxTimePickerVisible:function(e){var t=this;e&&this.$nextTick(function(){return t.$refs.maxTimePicker.ajustScrollTop()})},value:function(e){e?Array.isArray(e)&&(this.minDate=e[0]?(0,a.toDate)(e[0]):null,this.maxDate=e[1]?(0,a.toDate)(e[1]):null,this.minDate&&(this.date=new Date(this.minDate)),this.handleConfirm(!0)):(this.minDate=null,this.maxDate=null)}},methods:{handleClear:function(){this.minDate=null,this.maxDate=null,this.date=this.$options.defaultValue?f(this.$options.defaultValue):new Date,this.handleConfirm(!1)},handleDateInput:function(e,t){var i=e.target.value,n=(0,a.parseDate)(i,"yyyy-MM-dd");if(n){if("function"==typeof this.disabledDate&&this.disabledDate(new Date(n)))return;var r=new Date("min"===t?this.minDate:this.maxDate);r&&(r.setFullYear(n.getFullYear()),r.setMonth(n.getMonth(),n.getDate()))}},handleChangeRange:function(e){this.minDate=e.minDate,this.maxDate=e.maxDate,this.rangeState=e.rangeState},handleDateChange:function(e,t){var i=e.target.value,n=(0,a.parseDate)(i,"yyyy-MM-dd");if(n){var r=new Date("min"===t?this.minDate:this.maxDate);r&&(r.setFullYear(n.getFullYear()),r.setMonth(n.getMonth(),n.getDate())),"min"===t?r<this.maxDate&&(this.minDate=new Date(r.getTime())):r>this.minDate&&(this.maxDate=new Date(r.getTime()),this.minDate&&this.minDate>this.maxDate&&(this.minDate=null))}},handleTimeChange:function(e,t){var i=e.target.value,n=(0,a.parseDate)(i,"HH:mm:ss");if(n){var r=new Date("min"===t?this.minDate:this.maxDate);r&&(r.setHours(n.getHours()),r.setMinutes(n.getMinutes()),r.setSeconds(n.getSeconds())),"min"===t?r<this.maxDate&&(this.minDate=new Date(r.getTime())):r>this.minDate&&(this.maxDate=new Date(r.getTime())),this.$refs[t+"TimePicker"].value=r,this[t+"TimePickerVisible"]=!1}},handleRangePick:function(e){var t=!(arguments.length>1&&void 0!==arguments[1])||arguments[1];this.maxDate===e.maxDate&&this.minDate===e.minDate||(this.onPick&&this.onPick(e),this.maxDate=e.maxDate,this.minDate=e.minDate,t&&!this.showTime&&this.handleConfirm())},changeToToday:function(){this.date=new Date},handleShortcutClick:function(e){e.onClick&&e.onClick(this)},resetView:function(){this.minTimePickerVisible=!1,this.maxTimePickerVisible=!1},setTime:function(e,t){var i=new Date(e.getTime()),n=t.getHours(),a=t.getMinutes(),r=t.getSeconds();return i.setHours(n),i.setMinutes(a),i.setSeconds(r),new Date(i.getTime())},handleMinTimePick:function(e,t,i){this.minDate=this.minDate||new Date,e&&(this.minDate=this.setTime(this.minDate,e)),i||(this.minTimePickerVisible=t)},handleMaxTimePick:function(e,t,i){if(!this.maxDate){var n=new Date;n>=this.minDate&&(this.maxDate=new 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t=this;e=e||[],this.defaultExpandedKeys=e,e.forEach(function(e){var i=t.getNode(e);i&&i.expand(null,t.autoExpandParent)})},e.prototype.setChecked=function(e,t,i){var n=this.getNode(e);n&&n.setChecked(!!t,i)},e.prototype.getCurrentNode=function(){return this.currentNode},e.prototype.setCurrentNode=function(e){this.currentNode=e},e.prototype.setCurrentNodeKey=function(e){var t=this.getNode(e);t&&(this.currentNode=t)},e}();t.default=c},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}function a(e,t){if(!(e instanceof t))throw new TypeError("Cannot call a class as a function")}t.__esModule=!0,t.getChildState=void 0;var r=function(){function e(e,t){for(var i=0;i<t.length;i++){var n=t[i];n.enumerable=n.enumerable||!1,n.configurable=!0,"value"in n&&(n.writable=!0),Object.defineProperty(e,n.key,n)}}return function(t,i,n){return i&&e(t.prototype,i),n&&e(t,n),t}}(),s=i(64),o=n(s),l=i(238),c=t.getChildState=function(e){for(var 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t)t.hasOwnProperty(i)&&(this[i]=t[i]);this.level=0,this.loaded=!1,this.childNodes=[],this.loading=!1,this.parent&&(this.level=this.parent.level+1);var n=this.store;if(!n)throw new Error("[Node]store is required!");n.registerNode(this);var r=n.props;if(r&&"undefined"!=typeof r.isLeaf){var s=h(this,"isLeaf");"boolean"==typeof s&&(this.isLeafByUser=s)}if(n.lazy!==!0&&this.data?(this.setData(this.data),n.defaultExpandAll&&(this.expanded=!0)):this.level>0&&n.lazy&&n.defaultExpandAll&&this.expand(),this.data){var o=n.defaultExpandedKeys,l=n.key;l&&o&&o.indexOf(this.key)!==-1&&this.expand(null,n.autoExpandParent),l&&void 0!==n.currentNodeKey&&this.key===n.currentNodeKey&&(n.currentNode=this),n.lazy&&n._initDefaultCheckedNode(this),this.updateLeafState()}}return e.prototype.setData=function(e){Array.isArray(e)||(0,l.markNodeData)(this,e),this.data=e,this.childNodes=[];var t=void 0;t=0===this.level&&this.data instanceof Array?this.data:h(this,"children")||[];for(var i=0,n=t.length;i<n;i++)this.insertChild({data:t[i]})},e.prototype.insertChild=function(t,i){if(!t)throw new Error("insertChild error: child is required.");t instanceof e||((0,o.default)(t,{parent:this,store:this.store}),t=new e(t)),t.level=this.level+1,"undefined"==typeof i||i<0?this.childNodes.push(t):this.childNodes.splice(i,0,t),this.updateLeafState()},e.prototype.insertBefore=function(e,t){var i=void 0;t&&(i=this.childNodes.indexOf(t)),this.insertChild(e,i)},e.prototype.insertAfter=function(e,t){var i=void 0;t&&(i=this.childNodes.indexOf(t),i!==-1&&(i+=1)), this.insertChild(e,i)},e.prototype.removeChild=function(e){var t=this.childNodes.indexOf(e);t>-1&&(this.store&&this.store.deregisterNode(e),e.parent=null,this.childNodes.splice(t,1)),this.updateLeafState()},e.prototype.removeChildByData=function(e){var t=null;this.childNodes.forEach(function(i){i.data===e&&(t=i)}),t&&this.removeChild(t)},e.prototype.expand=function(e,t){var i=this,n=function(){if(t)for(var n=i.parent;n.level>0;)n.expanded=!0,n=n.parent;i.expanded=!0,e&&e()};this.shouldLoadData()?this.loadData(function(e){e instanceof Array&&(d(i),n())}):n()},e.prototype.doCreateChildren=function(e){var t=this,i=arguments.length>1&&void 0!==arguments[1]?arguments[1]:{};e.forEach(function(e){t.insertChild((0,o.default)({data:e},i))})},e.prototype.collapse=function(){this.expanded=!1},e.prototype.shouldLoadData=function(){return this.store.lazy===!0&&this.store.load&&!this.loaded},e.prototype.updateLeafState=function(){if(this.store.lazy===!0&&this.loaded!==!0&&"undefined"!=typeof this.isLeafByUser)return void(this.isLeaf=this.isLeafByUser);var e=this.childNodes;return!this.store.lazy||this.store.lazy===!0&&this.loaded===!0?void(this.isLeaf=!e||0===e.length):void(this.isLeaf=!1)},e.prototype.setChecked=function(e,t,i,n){var a=this;this.indeterminate="half"===e,this.checked=e===!0;var r=c(this.childNodes),s=r.all,o=r.allWithoutDisable;this.childNodes.length&&!s&&o&&(this.checked=!1,e=!1);var l=function(i){if(t&&!i){for(var r=a.childNodes,s=0,o=r.length;s<o;s++){var l=r[s];n=n||e!==!1;var u=l.disabled?l.checked:n;l.setChecked(u,t,!0,n)}var d=c(r),h=d.half,f=d.all;f||(a.checked=f,a.indeterminate=h)}};!this.store.checkStrictly&&this.shouldLoadData()?this.loadData(function(){l(!0)},{checked:e!==!1}):l();var d=this.parent;d&&0!==d.level&&(this.store.checkStrictly||i||u(d))},e.prototype.getChildren=function(){var e=this.data;if(!e)return null;var t=this.store.props,i="children";return t&&(i=t.children||"children"),void 0===e[i]&&(e[i]=null),e[i]},e.prototype.updateChildren=function(){var e=this,t=this.getChildren()||[],i=this.childNodes.map(function(e){return e.data}),n={},a=[];t.forEach(function(e,t){e[l.NODE_KEY]?n[e[l.NODE_KEY]]={index:t,data:e}:a.push({index:t,data:e})}),i.forEach(function(t){n[t[l.NODE_KEY]]||e.removeChildByData(t)}),a.forEach(function(t){var i=t.index,n=t.data;e.insertChild({data:n},i)}),this.updateLeafState()},e.prototype.loadData=function(e){var t=this,i=arguments.length>1&&void 0!==arguments[1]?arguments[1]:{};if(this.store.lazy!==!0||!this.store.load||this.loaded||this.loading&&!Object.keys(i).length)e&&e.call(this);else{this.loading=!0;var n=function(n){t.loaded=!0,t.loading=!1,t.childNodes=[],t.doCreateChildren(n,i),t.updateLeafState(),e&&e.call(t,n)};this.store.load(this,n)}},r(e,[{key:"label",get:function(){return h(this,"label")}},{key:"icon",get:function(){return h(this,"icon")}},{key:"key",get:function(){var e=this.store.key;return this.data?this.data[e]:null}},{key:"disabled",get:function(){return h(this,"disabled")}}]),e}();t.default=p},function(e,t){"use strict";t.__esModule=!0;var i=t.NODE_KEY="$treeNodeId";t.markNodeData=function(e,t){t[i]||Object.defineProperty(t,i,{value:e.id,enumerable:!1,configurable:!1,writable:!1})},t.getNodeKey=function(e,t){return e?t[e]:t[i]}},function(e,t,i){var n=i(5)(i(240),i(241),null,null,null);e.exports=n.exports},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(49),r=n(a),s=i(130),o=n(s),l=i(15),c=n(l);t.default={name:"ElTreeNode",componentName:"ElTreeNode",mixins:[c.default],props:{node:{default:function(){return{}}},props:{},renderContent:Function},components:{ElCollapseTransition:r.default,ElCheckbox:o.default,NodeContent:{props:{node:{required:!0}},render:function(e){var t=this.$parent,i=this.node,n=i.data,a=i.store;return t.renderContent?t.renderContent.call(t._renderProxy,e,{_self:t.tree.$vnode.context,node:i,data:n,store:a}):e("span",{class:"el-tree-node__label"},[this.node.label])}}},data:function(){return{tree:null,expanded:!1,childNodeRendered:!1,showCheckbox:!1,oldChecked:null,oldIndeterminate:null}},watch:{"node.indeterminate":function(e){this.handleSelectChange(this.node.checked,e)},"node.checked":function(e){this.handleSelectChange(e,this.node.indeterminate)},"node.expanded":function(e){this.expanded=e,e&&(this.childNodeRendered=!0)}},methods:{getNodeKey:function(e,t){var i=this.tree.nodeKey;return i&&e?e.data[i]:t},handleSelectChange:function(e,t){this.oldChecked!==e&&this.oldIndeterminate!==t&&this.tree.$emit("check-change",this.node.data,e,t),this.oldChecked=e,this.indeterminate=t},handleClick:function(){var e=this.tree.store;e.setCurrentNode(this.node),this.tree.$emit("current-change",e.currentNode?e.currentNode.data:null,e.currentNode),this.tree.currentNode=this,this.tree.expandOnClickNode&&this.handleExpandIconClick(),this.tree.$emit("node-click",this.node.data,this.node,this)},handleExpandIconClick:function(){this.node.isLeaf||(this.expanded?(this.tree.$emit("node-collapse",this.node.data,this.node,this),this.node.collapse()):(this.node.expand(),this.$emit("node-expand",this.node.data,this.node,this)))},handleCheckChange:function(e){this.node.setChecked(e.target.checked,!this.tree.checkStrictly)},handleChildNodeExpand:function(e,t,i){this.broadcast("ElTreeNode","tree-node-expand",t),this.tree.$emit("node-expand",e,t,i)}},created:function(){var e=this,t=this.$parent;t.isTree?this.tree=t:this.tree=t.tree;var i=this.tree;i||console.warn("Can not find node's tree.");var n=i.props||{},a=n.children||"children";this.$watch("node.data."+a,function(){e.node.updateChildren()}),this.showCheckbox=i.showCheckbox,this.node.expanded&&(this.expanded=!0,this.childNodeRendered=!0),this.tree.accordion&&this.$on("tree-node-expand",function(t){e.node!==t&&e.node.collapse()})}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{directives:[{name:"show",rawName:"v-show",value:e.node.visible,expression:"node.visible"}],staticClass:"el-tree-node",class:{"is-expanded":e.childNodeRendered&&e.expanded,"is-current":e.tree.store.currentNode===e.node,"is-hidden":!e.node.visible},on:{click:function(t){t.stopPropagation(),e.handleClick(t)}}},[i("div",{staticClass:"el-tree-node__content",style:{"padding-left":(e.node.level-1)*e.tree.indent+"px"}},[i("span",{staticClass:"el-tree-node__expand-icon",class:{"is-leaf":e.node.isLeaf,expanded:!e.node.isLeaf&&e.expanded},on:{click:function(t){t.stopPropagation(),e.handleExpandIconClick(t)}}}),e.showCheckbox?i("el-checkbox",{attrs:{indeterminate:e.node.indeterminate,disabled:!!e.node.disabled},on:{change:e.handleCheckChange},nativeOn:{click:function(e){e.stopPropagation()}},model:{value:e.node.checked,callback:function(t){e.node.checked=t},expression:"node.checked"}}):e._e(),e.node.loading?i("span",{staticClass:"el-tree-node__loading-icon 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i("el-tree-node",{key:e.getNodeKey(t),attrs:{node:t,props:e.props,"render-content":e.renderContent},on:{"node-expand":e.handleNodeExpand}})}),e.root.childNodes&&0!==e.root.childNodes.length?e._e():i("div",{staticClass:"el-tree__empty-block"},[i("span",{staticClass:"el-tree__empty-text"},[e._v(e._s(e.emptyText))])])],2)},staticRenderFns:[]}},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(244),r=n(a);r.default.install=function(e){e.component(r.default.name,r.default)},t.default=r.default},function(e,t,i){var n=i(5)(i(245),i(246),null,null,null);e.exports=n.exports},function(e,t){"use strict";t.__esModule=!0;var 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e=this.disabled?this.textTemplate.replace(/\{\s*value\s*\}/,this.value):this.texts[Math.ceil(this.currentValue)-1]},decimalStyle:function(){var e="";return this.disabled&&(e=(this.valueDecimal<50?0:50)+"%"),this.allowHalf&&(e="50%"),{color:this.activeColor,width:e}},valueDecimal:function(){return 100*this.value-100*Math.floor(this.value)},decimalIconClass:function(){return this.getValueFromMap(this.value,this.classMap)},voidClass:function(){return this.disabled?this.classMap.disabledVoidClass:this.classMap.voidClass},activeClass:function(){return this.getValueFromMap(this.currentValue,this.classMap)},colorMap:function(){return{lowColor:this.colors[0],mediumColor:this.colors[1],highColor:this.colors[2],voidColor:this.voidColor,disabledVoidColor:this.disabledVoidColor}},activeColor:function(){return this.getValueFromMap(this.currentValue,this.colorMap)},classes:function(){var e=[],t=0,i=this.currentValue;for(this.allowHalf&&this.currentValue!==Math.floor(this.currentValue)&&i--;t<i;t++)e.push(this.activeClass);for(;t<this.max;t++)e.push(this.voidClass);return e}},watch:{value:function(e){this.$emit("change",e),this.currentValue=e,this.pointerAtLeftHalf=this.value!==Math.floor(this.value)}},methods:{getValueFromMap:function(e,t){var i="";return i=e<=this.lowThreshold?t.lowColor||t.lowClass:e>=this.highThreshold?t.highColor||t.highClass:t.mediumColor||t.mediumClass},showDecimalIcon:function(e){var t=this.disabled&&this.valueDecimal>0&&e-1<this.value&&e>this.value,i=this.allowHalf&&this.pointerAtLeftHalf&&e-.5<=this.currentValue&&e>this.currentValue;return t||i},getIconStyle:function(e){var t=this.disabled?this.colorMap.disabledVoidColor:this.colorMap.voidColor;return{color:e<=this.currentValue?this.activeColor:t}},selectValue:function(e){this.disabled||(this.allowHalf&&this.pointerAtLeftHalf?this.$emit("input",this.currentValue):this.$emit("input",e))},setCurrentValue:function(e,t){if(!this.disabled){if(this.allowHalf){var i=t.target;(0,n.hasClass)(i,"el-rate__item")&&(i=i.querySelector(".el-rate__icon")),(0,n.hasClass)(i,"el-rate__decimal")&&(i=i.parentNode),this.pointerAtLeftHalf=2*t.offsetX<=i.clientWidth,this.currentValue=this.pointerAtLeftHalf?e-.5:e}else this.currentValue=e;this.hoverIndex=e}},resetCurrentValue:function(){this.disabled||(this.allowHalf&&(this.pointerAtLeftHalf=this.value!==Math.floor(this.value)),this.currentValue=this.value,this.hoverIndex=-1)}},created:function(){this.value||this.$emit("input",0),this.classMap={lowClass:this.iconClasses[0],mediumClass:this.iconClasses[1],highClass:this.iconClasses[2],voidClass:this.voidIconClass,disabledVoidClass:this.disabledVoidIconClass}}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"el-rate"},[e._l(e.max,function(t){return i("span",{staticClass:"el-rate__item",style:{cursor:e.disabled?"auto":"pointer"},on:{mousemove:function(i){e.setCurrentValue(t,i)},mouseleave:e.resetCurrentValue,click:function(i){e.selectValue(t)}}},[i("i",{staticClass:"el-rate__icon",class:[e.classes[t-1],{hover:e.hoverIndex===t}],style:e.getIconStyle(t)},[e.showDecimalIcon(t)?i("i",{staticClass:"el-rate__decimal",class:e.decimalIconClass,style:e.decimalStyle}):e._e()])])}),e.showText?i("span",{staticClass:"el-rate__text",style:{color:e.textColor}},[e._v(e._s(e.text))]):e._e()],2)},staticRenderFns:[]}},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(321),r=n(a);r.default.install=function(e){e.component(r.default.name,r.default)},t.default=r.default},function(e,t,i){var n=i(5)(i(322),i(323),null,null,null);e.exports=n.exports},function(e,t){"use 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a=i(325),r=n(a);r.default.install=function(e){e.component(r.default.name,r.default)},t.default=r.default},function(e,t,i){var n=i(5)(i(326),i(327),null,null,null);e.exports=n.exports},function(e,t){"use strict";t.__esModule=!0,t.default={name:"ElStep",props:{title:String,icon:String,description:String,status:String},data:function(){return{index:-1,lineStyle:{},mainOffset:0,internalStatus:""}},beforeCreate:function(){this.$parent.steps.push(this)},beforeDestroy:function(){var e=this.$parent.steps,t=e.indexOf(this);t>=0&&e.splice(t,1)},computed:{currentStatus:function(){return this.status||this.internalStatus},prevStatus:function(){var e=this.$parent.steps[this.index-1];return e?e.currentStatus:"wait"},isLast:function(){var e=this.$parent;return e.steps[e.steps.length-1]===this},style:function(){var e=this.$parent,t=e.center,i=e.steps.length;if(t&&this.isLast)return{};var n="number"==typeof e.space?e.space+"px":e.space?e.space:100/(t?i-1:i)+"%";return"horizontal"===e.direction?{width:n}:this.isLast?void 0:{height:n}}},methods:{updateStatus:function(e){var t=this.$parent.$children[this.index-1];e>this.index?this.internalStatus=this.$parent.finishStatus:e===this.index&&"error"!==this.prevStatus?this.internalStatus=this.$parent.processStatus:this.internalStatus="wait",t&&t.calcProgress(this.internalStatus)},calcProgress:function(e){var t=100,i={};i.transitionDelay=150*this.index+"ms",e===this.$parent.processStatus?t="error"!==this.currentStatus?50:0:"wait"===e&&(t=0,i.transitionDelay=-150*this.index+"ms"),i.borderWidth=t?"1px":0,"vertical"===this.$parent.direction?i.height=t+"%":i.width=t+"%",this.lineStyle=i}},mounted:function(){var e=this,t=this.$parent;"horizontal"===t.direction&&t.alignCenter&&(this.mainOffset=-this.$refs.title.getBoundingClientRect().width/2+16+"px");var i=this.$watch("index",function(t){e.$watch("$parent.active",e.updateStatus,{immediate:!0}),i()})}}},function(e,t){e.exports={render:function(){var e=this,t=e.$createElement,i=e._self._c||t;return i("div",{staticClass:"el-step",class:["is-"+e.$parent.direction],style:[e.style,e.isLast?"":{marginRight:-e.$parent.stepOffset+"px"}]},[i("div",{staticClass:"el-step__head",class:["is-"+e.currentStatus,{"is-text":!e.icon}]},[i("div",{staticClass:"el-step__line",class:["is-"+e.$parent.direction,{"is-icon":e.icon}],style:e.isLast?"":{marginRight:e.$parent.stepOffset+"px"}},[i("i",{staticClass:"el-step__line-inner",style:e.lineStyle})]),i("span",{staticClass:"el-step__icon"},["success"!==e.currentStatus&&"error"!==e.currentStatus?e._t("icon",[e.icon?i("i",{class:["el-icon-"+e.icon]}):i("div",[e._v(e._s(e.index+1))])]):i("i",{class:["el-icon-"+("success"===e.currentStatus?"check":"close")]})],2)]),i("div",{staticClass:"el-step__main",style:{marginLeft:e.mainOffset}},[i("div",{ref:"title",staticClass:"el-step__title",class:["is-"+e.currentStatus]},[e._t("title",[e._v(e._s(e.title))])],2),i("div",{staticClass:"el-step__description",class:["is-"+e.currentStatus]},[e._t("description",[e._v(e._s(e.description))])],2)])])},staticRenderFns:[]}},function(e,t,i){"use 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t=this;this.items.forEach(function(i,n){i.translateItem(n,t.activeIndex,e)})},playSlides:function(){this.activeIndex<this.items.length-1?this.activeIndex++:this.activeIndex=0},pauseTimer:function(){clearInterval(this.timer)},startTimer:function(){this.interval<=0||!this.autoplay||(this.timer=setInterval(this.playSlides,this.interval))},setActiveItem:function(e){if("string"==typeof e){var t=this.items.filter(function(t){return t.name===e});t.length>0&&(e=this.items.indexOf(t[0]))}if(e=Number(e),!isNaN(e)&&e===Math.floor(e)){var i=this.items.length;e<0?this.activeIndex=i-1:e>=i?this.activeIndex=0:this.activeIndex=e}},prev:function(){this.setActiveItem(this.activeIndex-1)},next:function(){this.setActiveItem(this.activeIndex+1)},handleIndicatorClick:function(e){this.activeIndex=e},handleIndicatorHover:function(e){"hover"===this.trigger&&e!==this.activeIndex&&(this.activeIndex=e)}},created:function(){var 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e("div",{class:["el-scrollbar__bar","is-"+n.key],on:{mousedown:this.clickTrackHandler}},[e("div",{ref:"thumb",class:"el-scrollbar__thumb",on:{mousedown:this.clickThumbHandler},style:(0,a.renderThumbStyle)({size:t,move:i,bar:n})},[])])},methods:{clickThumbHandler:function(e){this.startDrag(e),this[this.bar.axis]=e.currentTarget[this.bar.offset]-(e[this.bar.client]-e.currentTarget.getBoundingClientRect()[this.bar.direction])},clickTrackHandler:function(e){var t=Math.abs(e.target.getBoundingClientRect()[this.bar.direction]-e[this.bar.client]),i=this.$refs.thumb[this.bar.offset]/2,n=100*(t-i)/this.$el[this.bar.offset];this.wrap[this.bar.scroll]=n*this.wrap[this.bar.scrollSize]/100},startDrag:function(e){e.stopImmediatePropagation(),this.cursorDown=!0,(0,n.on)(document,"mousemove",this.mouseMoveDocumentHandler),(0,n.on)(document,"mouseup",this.mouseUpDocumentHandler),document.onselectstart=function(){return!1}},mouseMoveDocumentHandler:function(e){if(this.cursorDown!==!1){var t=this[this.bar.axis];if(t){var i=(this.$el.getBoundingClientRect()[this.bar.direction]-e[this.bar.client])*-1,n=this.$refs.thumb[this.bar.offset]-t,a=100*(i-n)/this.$el[this.bar.offset];this.wrap[this.bar.scroll]=a*this.wrap[this.bar.scrollSize]/100}}},mouseUpDocumentHandler:function(e){this.cursorDown=!1,this[this.bar.axis]=0,(0,n.off)(document,"mousemove",this.mouseMoveDocumentHandler),document.onselectstart=null}},destroyed:function(){(0,n.off)(document,"mouseup",this.mouseUpDocumentHandler)}}},function(e,t){"use strict";function i(e){var t=e.move,i=e.size,n=e.bar,a={},r="translate"+n.axis+"("+t+"%)";return 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function(){}}}},data:function(){return{currentValue:this.value||[],menu:null,debouncedInputChange:function(){},menuVisible:!1,inputHover:!1,inputValue:"",flatOptions:null}},computed:{labelKey:function(){return this.props.label||"label"},valueKey:function(){return this.props.value||"value"},childrenKey:function(){return this.props.children||"children"},currentLabels:function(){var e=this,t=this.options,i=[];return this.currentValue.forEach(function(n){var a=t&&t.filter(function(t){return t[e.valueKey]===n})[0];a&&(i.push(a[e.labelKey]),t=a[e.childrenKey])}),i}},watch:{menuVisible:function(e){e?this.showMenu():this.hideMenu()},value:function(e){this.currentValue=e},currentValue:function(e){this.dispatch("ElFormItem","el.form.change",[e])},options:{deep:!0,handler:function(e){this.menu||this.initMenu(),this.flatOptions=this.flattenOptions(this.options),this.menu.options=e}}},methods:{initMenu:function(){this.menu=new r.default(o.default).$mount(),this.menu.options=this.options,this.menu.props=this.props,this.menu.expandTrigger=this.expandTrigger,this.menu.changeOnSelect=this.changeOnSelect,this.menu.popperClass=this.popperClass,this.popperElm=this.menu.$el,this.menu.$on("pick",this.handlePick),this.menu.$on("activeItemChange",this.handleActiveItemChange),this.menu.$on("menuLeave",this.doDestroy)},showMenu:function(){var e=this;this.menu||this.initMenu(),this.menu.value=this.currentValue.slice(0),this.menu.visible=!0,this.menu.options=this.options,this.$nextTick(function(t){e.updatePopper(),e.menu.inputWidth=e.$refs.input.$el.offsetWidth-2})},hideMenu:function(){this.inputValue="",this.menu.visible=!1},handleActiveItemChange:function(e){var t=this;this.$nextTick(function(e){t.updatePopper()}),this.$emit("active-item-change",e)},handlePick:function(e){var t=!(arguments.length>1&&void 0!==arguments[1])||arguments[1];this.currentValue=e,this.$emit("input",e),this.$emit("change",e),t?this.menuVisible=!1:this.$nextTick(this.updatePopper)},handleInputChange:function(e){var t=this;if(this.menuVisible){var i=this.flatOptions;if(!e)return this.menu.options=this.options,void this.$nextTick(this.updatePopper);var n=i.filter(function(i){return i.some(function(i){return new RegExp(e,"i").test(i[t.labelKey])})});n=n.length>0?n.map(function(i){return{__IS__FLAT__OPTIONS:!0,value:i.map(function(e){return e[t.valueKey]}),label:t.renderFilteredOptionLabel(e,i)}}):[{__IS__FLAT__OPTIONS:!0,label:this.t("el.cascader.noMatch"),value:"",disabled:!0}],this.menu.options=n,this.$nextTick(this.updatePopper)}},renderFilteredOptionLabel:function(e,t){var i=this;return t.map(function(t,n){var a=t[i.labelKey],r=a.toLowerCase().indexOf(e.toLowerCase()),s=a.slice(r,e.length+r),o=r>-1?i.highlightKeyword(a,s):a;return 0===n?o:[" / ",o]})},highlightKeyword:function(e,t){var i=this,n=this._c;return 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i=e.beforeFilter(t);i&&i.then?(e.menu.options=[{__IS__FLAT__OPTIONS:!0,label:e.t("el.cascader.loading"),value:"",disabled:!0}],i.then(function(){e.$nextTick(function(){e.handleInputChange(t)})})):i!==!1&&e.$nextTick(function(){e.handleInputChange(t)})})},mounted:function(){this.flatOptions=this.flattenOptions(this.options)}}},function(e,t,i){var n=i(5)(i(352),null,null,null,null);e.exports=n.exports},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(353),r=n(a),s=i(354),o=i(112),l=n(o),c=function e(t,i){if(!t||!Array.isArray(t)||!i)return t;var n=[],a=["__IS__FLAT__OPTIONS","label","value","disabled"],r=i.children||"children";return t.forEach(function(t){var s={};a.forEach(function(e){var n=i[e],a=t[n];void 0===a&&(n=e,a=t[n]),void 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i("div",{staticClass:"el-color-svpanel",style:{backgroundColor:e.background}},[i("div",{staticClass:"el-color-svpanel__white"}),i("div",{staticClass:"el-color-svpanel__black"}),i("div",{staticClass:"el-color-svpanel__cursor",style:{top:e.cursorTop+"px",left:e.cursorLeft+"px"}},[i("div")])])},staticRenderFns:[]}},function(e,t,i){var n=i(5)(i(367),i(368),null,null,null);e.exports=n.exports},function(e,t,i){"use strict";function n(e){return e&&e.__esModule?e:{default:e}}t.__esModule=!0;var a=i(364),r=n(a);t.default={name:"el-color-hue-slider",props:{color:{required:!0},vertical:Boolean},data:function(){return{thumbLeft:0,thumbTop:0}},computed:{hueValue:function(){var e=this.color.get("hue");return e}},watch:{hueValue:function(){this.update()}},methods:{handleClick:function(e){var t=this.$refs.thumb,i=e.target;i!==t&&this.handleDrag(e)},handleDrag:function(e){var t=this.$el.getBoundingClientRect(),i=this.$refs.thumb,n=void 0;if(this.vertical){var 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