PMC:1214551 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/1214551","sourcedb":"PMC","sourceid":"1214551","source_url":"https://www.ncbi.nlm.nih.gov/pmc/1214551","text":"Transcriptional repression of human cad gene by hypoxia inducible factor-1α \n\nAbstract\nDe novo biosynthesis of pyrimidine nucleotides provides essential precursors for DNA synthesis and cell proliferation. The first three steps of de novo pyrimidine biosynthesis are catalyzed by a multifunctional enzyme known as CAD (carbamoyl phosphate synthetase-aspartate carbamoyltransferase-dihydroorotase). In this work, a decrease in CAD expression is detected in numerous cell lines and primary culture human stromal cells incubated under hypoxia or desferrioxamine (DFO)-induced HIF-1α accumulation. A putative hypoxia response element (HRE) binding matrix is identified by analyzing human cad-gene promoter using a bioinformatic approach. Promoter activity assays, using constructs harboring the cad promoter (−710/+122) and the −67/HRE fragment (25-bases), respectively, demonstrate the suppression of reporter-gene expression under hypoxia. Suppression of cad-promoter activity is substantiated by forced expression of wild-type HIF-1α but abolished by overexpression of dominant-negative HIF-1α. A chromatin immunoprecipitation assay provides further evidence that HIF-1α binds to the cad promoter in vivo. These data demonstrate that the cad-gene expression is repressed by HIF-1α, which represents a functional link between hypoxia and cell-cycle arrest.\n\nINTRODUCTION\nHypoxia is an environmental stress that trigger with important implications in the pathogenesis of major causes of mortality including cancer, cerebral and myocardial ischemia, preeclampsia, and chronic heart and lung diseases. In recent years, many studies have shown that hypoxia can inhibit or even completely abolish cell proliferation (1–8), which is directly involved in the chemoresistance and radioresistance of hypoxic tumors because, chemo- and radiotherapy are efficient only against rapidly dividing cells. Thus, understanding the mechanisms responsible for cell-cycle arrest under hypoxic stress might help to circumvent these two forms of resistance.\nThe expression of hypoxia-responsive genes is regulated primarily by the transcription factor hypoxia-inducible factor (HIF). HIF consists of an inducible α subunit and a constitutively expressed β subunit. Three variants of HIF-α (HIF-1α, -2α and -3α) have been identified (9); all of them dimerize with HIF-1β (also known as aryl hydrocarbon nuclear translocator, ARNT) to form a heterodimeric functional unit. HIF-1α is expressed in most, if not all, human tissues (10), while HIF-2α and HIF-3α are expressed in more restricted tissues and developing stages such as the fetal lung and vascular endothelium (11–13). In addition, HIF-1α appears to play a general role in the transcriptional regulation of all cells in response to hypoxia, whereas HIF-2α and HIF-3α play more limited or specialized roles in oxygen homeostasis.\nRecent studies (1–3) have demonstrated that hypoxia may lead to apoptosis of some transformed cell lines, while non-transformed cells are viable under hypoxic condition but are arrested in the G1/S-phase. Upregulation of HIF-1α caused by hypoxia inhibits cell-cycle progression in most normal and cancer cells (4–8). However, the mechanism of HIF-1α-induced cell-cycle arrest has not been uniformly resolved. Hypoxia-induced cell-cycle arrest causes the elevation of checkpoint proteins such as p53, p21 and p27 in direct relation to the expression level of HIF-1α (3,14). In contrast, a recent study demonstrated that embryonic fibroblast cells without p21 and p27 are capable of hypoxia-induced S-phase arrest, but that re-entry into the cell-cycle after reoxygenation is delayed (8). Most importantly, direct evidence of the transcriptional regulation of these checkpoint proteins by HIF-1α has never been demonstrated. Therefore, it is hypothesized that the elevation of checkpoint proteins under hypoxia is the secondary barrier of cell-cycle arrest and that a nucleotide shortage is the primary cause of the arrest (1).\nThe de novo biosynthesis of pyrimidine nucleotides provides essential precursors for DNA synthesis and cell proliferation. Pyrimidine biosynthesis is not only a prerequisite for cells to enter the S-phase, but also it plays a dominant role in regulating cell-cycle progression due to the increased demand for nucleotides for DNA synthesis in rapidly proliferating cells. The first three steps of de novo pyrimidine biosynthesis are catalyzed by a multifunctional cytoplasmic enzyme known as CAD (carbamoyl phosphate synthetase-aspartate carbamoyltransferase-dihydroorotase) (15,16).\nOver the past decade, extensive advances have been made in elucidating the mechanisms of the de novo biosynthesis of pyrimidine nucleotide in mammalian cells. The cloning of the human cad gene and the characterization of its properties provided the major breakthrough for our understanding of the principles and regulation of pyrimidine biosynthesis in cancerous and non-cancerous cells. It is clear that CAD catalyzes the rate-limiting step in the de novo pyrimidine synthetic pathway (17), and that it therefore controls the rate of DNA synthesis. Transcriptional upregulation of cad promoter by growth factors and steroids that ultimately leads to an increase in cell proliferation has been reported. Mitogen-activated protein kinase (MAPK) and the transcription factor c-Myc mediates the growth-factor-induced CAD overexpression, and estrogen upregulates cad-promoter activity via the binding of ER and SP1 to the GC box of cad promoter (18,19).\nThe biosynthesis of pyrimidine nucleotides is inhibited by hypoxia, which ultimately leads to reduced DNA synthesis, hence inhibiting cell-cycle progression (7,20,21). Addition of exogenous pyrimidine nucleotides causes re-entry into the S-phase and initiates replication in hypoxic cells (7). Because CAD controls the first three enzymatic activities of pyrimidine nucleotide biosynthesis, reducing pyrimidine nucleotide production in hypoxic cells may be mediated by inhibiting CAD expression. Furthermore, HIF-1α is the master transcription factor in regulating hypoxia-responsive gene expression; thus, we hypothesize that HIF-1α may directly inhibit cad under hypoxia condition. This study aims to investigate regulation of CAD by HIF-1α using both in vitro and in vivo approaches.\n\nMATERIALS AND METHODS\n\nCell culture and hypoxia treatment\nCell lines were maintained in specific culture media recommended by the American Type Culture Collection (ATCC), and were supplemented with 10% fetal bovine serum (FBS). The human endometrial stromal cells were purified and cultured in DMEM/F12 medium with 10% FBS, as previously described (22,23). Between 18–24 h before undergoing hypoxia, cells were plated at a density of 5 × 105 cells per 30 mm glass dish. The medium was changed ∼1 h before treatment to assure an adequate amount of nutrient and growth factor. Hypoxic treatment was carried out in an incubator with 1% O2, 5% CO2 and 94% N2, or with desferrioxamine (DFO), as indicated. Oxygen concentration was monitored using an oxygen electrode (OS1000; Oxygen Sensors, Inc, Frazer, PA).\n\nRNA isolation and real-time RT–PCR\nTotal RNA was isolated from cells using a kit (RNeasy Mini Kit; Qiagen, Valencia, CA) according to the manufacturer's instructions. RNA concentrations were determined using UV-absorption at 260 nm, and then subjected to reverse-transcription at 42°C for 60 min, denaturing, and PCR amplification using a thermal cycler (ABI 7900; Applied Biosystems, Foster City, CA). To determine the amounts of CAD transcript, real-time RT–PCR was conducted. In this reaction, SYBR Green I was added to the PCR master mix and served as a fluorescence source for laser detection. The cycling conditions were 95°C for 10 min, 40 cycles at 95°C for 15 s and 60°C for 1 min. The reaction data were expressed as copies/µg of RNA, after converting the number of cycle thresholds (Ct)-the PCR cycle number at which the fluorescent signal in each reaction reaches a preset threshold above background-to absolute value according to the standard curve. A dissociation curve was created using the built-in melting-curve program to confirm the presence of a single PCR product. 18S rRNA was used as an internal control, for which the primer sequences were previously reported (24).\n\nPlasmids, transfection, and promoter-activity assays\nHuman HIF-1α CEP4/HIF-1α (ATCC Cat no.: MBA-2) and dominant-negative form HIF-α pCEP4/HIF-1αDN (ATCC Cat no.: MBA-7) plasmids were purchased from the American Type Culture Collection (ATCC, The Johns Hopkins University, Baltimore, MD). Human cad promoter (−710/+122) was cloned to pGL3 basic vector (Promega Corp., Madison, WI) using PCR with a pair of primers: (forward: 5′-ctagctagctagAAAGGAGAGCCACAAGACCA-3′; reverse: 5′-ccgctcgagcggGGAAGGACTGCAAACTCCAC-3′), which contained NheI and XhoI restriction sites (underlined), respectively. Alternatively, two 25-base oligonucleotides: (forward: 5′-ctagCCGCCCCTTACGTGCCCGGCCCCGC-3′, reverse: 5′-tcgaGCGGGGCCGGGCACGTAAGGGGCGG-3′) corresponding to human cad HRE matrix (−76/−52) were synthesized and cloned into SV40-driven pGL3 plasmid after annealing. Mutation of the putative HRE sequence was achieved by replacing the bases ACGTG with ATTAG.\nCells were placed on 24-well plates for luciferase assays. Commercial plasmids containing a CMV-driven β-galactosidase reporter system (Promega, Madison, WI) were transfected into the cells using Lipofectamine 2000 (Invitrogen Life Technologies, Carlsbad, CA). After transfection, the cells were allowed to rise and incubated in serum-free DMEM/F12 medium for 6 h. The medium was then changed, and cells were subjected to hypoxic treatment for the indicated time. Luciferase assays were done using a kit (Dual Luciferase Reporter Assay System, Promega) according to the manufacturer's instructions. Briefly, 100 µl of luciferase substrates were added to 20 µl of lysate, and luciferase activity was measured using a 20/20 luminometer (Turner Designs, Sunnyvale, CA). Each luciferase assay experiment was performed in duplicate and repeated as indicated in the figure legends.\n\nSiRNA\nShort interference RNA (siRNA) against human HIF-1α was synthesized by Qiagen. Sequences for siHIF-1α are: 5′-r(CUGAUGACCAGCAACUUGA)d(TT)-3′ and 5′-r(UCAAGUUGCUGGUCAUCAUCAG)d(TT)-3′. For negative control, two ribonucleotides with scrambled sequences 5′-r(AGUUCAACGACCAGUAGUC)d(TT)-3′ and 5′-r(GACUACUGGUCGUUGAACU)d(TT)-3′ were also synthesized. The ribonucleotides were dissolved in the siRNA suspension buffer (Qiagen), heated to 90°C for 1 min, and incubated at 37°C for 60 min. The annealed siRNA (5 µg) was used to transfect cells according to manufacturer's instruction (Qiagen). After transfection, cells were incubated with or without 10 mM DFO for 8 h and subjected to RNA isolation and real-time RT–PCR quantification as described above.\n\nChromatin immunoprecipitation (ChIP)-PCR assay\nThe protocol used was as described before (24) with modifications. In brief, proteins (HIF-1α) and DNA in normoxia, hypoxia, or DFO-treated cells (1 × 106 cells) were cross-linked by incubation for 10 min at 37°C with a final concentration of 1% formaldehyde. After aspiration of the formaldehyde, the cells were washed twice with ice-cold phosphate-buffered saline (PBS) containing protease inhibitors (1 mM phenylmethylsulfonyl fluoride and 1 µg/ml each of aprotinin, and pepstatin A) and scraped into a conical tube. The lysate was then centrifuged in a desktop centrifuge (Model 5415R, Eppendorf, Hamburg, Germany) for 5 min at 500 g at 4°C, resuspended in 400 µl of lysis buffer [1% SDS, 10 mM EDTA, and 50 mM Tris–HCl (pH 8.1)], and placed on ice for 10 min. Genomic DNA was sheared to lengths of 0.5–1 kb by sonicating the cell lysate, then debris was removed by centrifugation, and the supernatant diluted with 1 ml of ChIP dilution buffer [0.01% SDS, 1.1% Triton X-100, 1.2 mM EDTA, 16.7 mM Tris–HCl, 16.7 mM NaCl and proteinase inhibitors (pH 8.0)]. Two percent of the diluted lysate was kept for input control. The chromatin solution was pre-cleared with mixtures containing BSA, salmon sperm DNA and protein A Sepharose. Anti-HIF-1α antibody or rabbit IgG (for negative control) was added to the supernatant fraction and the mixture was incubated overnight at 4°C with rotation. Then, 60 µl of salmon sperm DNA/Protein A agarose slurry was added to the mixture and incubated for 1 h at 4°C with rotation. The protein A agarose/antibody/HIF-1α complex was pelleted by gentle centrifugation (400 g at 4°C for 1 min) in a desktop centrifuge (Eppendorf, Model 5415R). The pellet was washed sequentially (5 min per wash) on a rotating platform with 1 ml each of low salt washing buffer [0.1% SDS, 1% Triton X-100, 2 mM EDTA, 20 mM Tris–HCl and 150 mM NaCl (pH 8.0)], high salt washing buffer [0.1% SDS, 1% Triton X-100, 2 mM EDTA, 20 mM Tris–HCl and 500 mM NaCl (pH 8.0)], LiCl washing buffer [0.25 M LiCl, 1% NP-40, 1% sodium deoxycholate, 1 mM EDTA and 10 mM Tris–HCl (pH 8.0)] and 1× TE buffer [10 mM Tris–HCl and 1 mM EDTA (pH 8.0)]. After the final wash, the pellet was eluted by resuspension in freshly made elution buffer (1% SDS and 50 mM NaHCO3), followed by centrifugation. Twenty microliters of 5 M NaCl was added to the supernatant and the mixture incubated for 4 h at 65°C to reverse the protein–DNA crosslinking, and then the DNA was amplified using PCR. The cycling conditions were 95°C for 10 min, followed by 30 cycles of 95°C for 30 s, 60°C for 30 s and 72°C for 30 s.\n\nStatistical analysis\nThe data were expressed as mean ± standard error of the mean (SEM). Differences between groups were analyzed using one-way ANOVA in commercial statistical software (GraphPad Prism 4.02; GraphPad Software, San Diego, CA). Tukey's procedure was used to test differences between groups found significant using the F-test. Student's t-test was used to compare differences between normoxic and hypoxic groups. Statistical significance was set at P \u003c 0.05.\n\nRESULTS\n\nExpression of CAD is cell-cycle-dependent\nThe expression of CAD provides a functional enzyme for the biosynthesis of pyrimidine nucleotides, the critical constituent for DNA synthesis and cell-cycle progression. To determine the expression levels of CAD in different cell types, mRNA encoding for CAD was quantified using real-time RT–PCR. The expression level of CAD was associated with the proliferation speed of each cancer cell line. Expression levels for the colo320DM and IMR32 lines (doubling time: ≤ 24 h) were significantly higher than for the primary cultured endometrial stromal cells (doubling time: \u003e 48 h) (Figure 1). In addition, expression of CAD was cell-cycle-dependent. In colo320DM cells, CAD transcripts increased 4 h after serum stimulation, reached peak value at 8 h, returned to basal level at 16 h, and rose again at 24 h (Figure 1). Levels of CAD mRNA in IMR32 did not increase until 8 h after serum stimulation, maintained at the high value at 16 h, and returned to basal level at 24 h (Figure 1). In stromal cells, which showed no measurable proliferation within 24 h after serum stimulation, the CAD level predictably did not change (Figure 1).\n\nHypoxia inhibits the expression of CAD mRNA\nIn order to investigate whether the expression of CAD is regulated by hypoxia, we compared the mRNA levels of CAD in cells cultured under normoxic (21% O2) or hypoxic (1% O2) conditions. In colo320DM cells exposed to hypoxia, CAD mRNA expression was significantly reduced at all time points (Figure 2A). To test whether hypoxia-induced suppression of CAD mRNA expression is a common effect, three other cell lines (A293T, IMR32 and HeLa) and human endometrial stromal cells were exposed to normoxia or hypoxia for 16 h, and their levels of mRNA were analyzed. Hypoxia treatment significantly inhibited CAD mRNA expression in all cells tested (Figure 2B), which indicated that it is a common phenomenon. It has been reported that hypoxia may induce apoptosis in p53+/+ cells (2). To test whether the decrease in CAD mRNA expression under hypoxia condition is due to hypoxia-induced cell death, cell numbers were calculated 16 h after hypoxia treatment. No significant decreases in cell numbers were observed in any of the cell lines used (data not shown). In addition, expression of another hypoxia-regulated gene, VEGF, was examined using simple RT–PCR as an internal control because hypoxia induces VEGF expression in many cell types and solid tumors. In fact, VEGF expression increased in cells exposed to hypoxia for 24 h even though CAD mRNA expression decreased (Figure 2C). Together, these data demonstrate that hypoxia specifically suppressed CAD mRNA expression.\n\nSuppression of CAD expression under chemical hypoxia\nHypoxia-regulated gene expression is either HIF-1-dependent or HIF-1-independent. To determine whether suppression of CAD expression under hypoxia is mediated by HIF-1, cells were treated with DFO, an iron chelator that causes HIF-1α to accumulate. DFO treatment caused a dose-dependent increase in nuclear HIF-1α (Figure 3A). A time-course experiment demonstrated that accumulation of HIF-1α had discernibly accumulated in the nucleus 4 h after treatment in colo320DM cells, peaked at 8 h, and remained for at least 24 h (Figure 3A, D4, D8, D16, D24). Similarly, the expression of CAD was time-dependently suppressed after treatment with DFO under normoxic conditions (Figure 3B). Although the suppression pattern was somewhat different in different cell types, it seems clear that DFO reduced CAD expression in all four cell lines (colo320DM, HeLa, A293T and IMR32) as well as in the primary cultured stromal cells (Figure 3B). Again, the cell number did not decrease (data not shown) and DFO upregulated the expression of VEGF mRNA (Figure 3C and data not shown), which indicated DFO did not induce apoptosis in these cells within 24 h.\n\nIdentification of functional HRE in human cad-gene promoter\nBased on these data, we investigated whether repression of CAD by hypoxia could be regulated by HIF-1 at the transcriptional level. The sequence of cad promoter, available in the human genome database (Ensembl), was retrieved and analyzed for putative HRE sites using a hidden Markov model (HMM). An HRE matrix-containing the core sequence (5′-RCGTG-3′) was identified at the −67/−54 of cad promoter (Figure 4A). To test whether this HRE matrix is functional, the 5′-flanking sequence of human cad (−710/+122) was cloned to a pGL3 basic luciferase reporter plasmid. Exposing cells transiently transfected with plasmid containing cad promoter to 1% oxygen significantly reduced reporter-gene expression (Figure 4B); the reduction was inversely correlated with the elevation of HIF-1α in the nucleus (Figure 4C). This result was indisputably replicated in primary culture cells and three other cell lines (Figure 4D and data not shown) indicating, again, that it is a common event. Because DFO treatment also reduced CAD expression, we tested whether DFO suppressed cad-promoter activity. As expected, treatment with DFO dose-dependently reduced reporter-gene expression in cells transfected with plasmids containing cad promoter (Figure 4E).\nOne study reported that the core HRE (5′-RCGTG-3′) is necessary but not sufficient for HIF-mediated promoter activity (25). To test whether this HRE matrix is indeed a functional HIF-1-regulated region, two 25 bp oligonucleotides corresponding to the −76/−52 segment of the human cad-gene promoter region were synthesized and cloned to an SV40 promoter containing pGL3 plasmid (Figure 5A). Insertion of the HRE matrix into pGL3-SV40 plasmid caused a 2-fold increase in promoter activity when cells were cultured in normoxic conditions (Figure 5B). When exposed to hypoxia, reporter-gene expression decreased in cells transfected with this HRE-containing plasmid (Figure 5B).\nTo examine whether the effect of cad HRE was due to alteration of intact SV40 promoter, a 47 bp VEGF HRE (26) was cloned to the same position in the pGL3-SV40 plasmid, and luciferase activity was measured. The VEGF HRE did not alter promoter activity under normoxic conditions but it did induce reporter-gene expression under hypoxic conditions (Figure 5B). Similarly, cells transfected with plasmid containing the HRE matrix of the cad gene showed reduced promoter activity after being treated with 10 mM DFO (Figure 5C). In contrast, DFO treatment did not inhibit reporter-gene expression in cells transfected with plasmids containing mutated HRE matrix (Figure 5C). Forced expression of wild-type HIF-1α significantly inhibited cad-promoter activity and this effect was further substantiated by DFO treatment (Figure 5D). Inversely, transfection with dominant-negative HIF-1α plasmid dose-dependently restored cad-promoter activity inhibited by DFO treatment (Figure 5E). DFO treatment induced reporter-gene activity in cells co-transfected with pVEGF-SV40 and control plasmid, but this effect was abolished by overexpression of dominant-negative HIF-1α (Figure 5F). Taken together, these data provide further evidence that supports the functional role of HIF-1α in transcriptional repression of cad-gene activity in a gene-specific manner.\n\nSuppression of cad-gene expression under hypoxia is HIF-1α dependent\nTo determine the crucial role of HIF-1α in hypoxia-mediated down-regulation of cad-gene expression, specific siRNA against HIF-1α was used to knock down HIF-1α and expression of CAD transcripts were determined under chemical hypoxia. Transfection of HIF-1α siRNA (siHIF) significantly inhibited DFO-induced HIF-1α protein accumulation while transfection of siRNA with scrambled sequence (sr-HIF) did not have similar effect (Figure 6A). Levels of endogenous CAD transcripts were significantly decreased in mock transfected cells treated with DFO (Figure 6B). The suppressive effect was reversed by prior transfection with siHIF-1α but not sr-HIF (Figure 6B) indicating suppression of CAD expression by DFO is HIF-1α dependent.\n\nBinding of HIF-1α to the cad-promoter HRE\nSo far, we have identified that HIF-1α transcriptionally inhibits cad-gene expression. To demonstrate that HIF-1α physically binds to the cad-promoter HRE matrix and regulates cad-gene activity, colo320DM cells were exposed to normoxia or hypoxia for different periods of time, and the binding of HIF-1α to cad promoter was analyzed using a ChIP assay. HIF-1α bound significantly to the cad promoter by 16 h after hypoxia treatment (Figure 7A). In contrast, non-specific binding was unaffected by hypoxia treatment, as demonstrated by results using rabbit IgG as the primary antibody for immunoprecipitation (Figure 7A). Similar results were obtained when cells were treated with 1 mM DFO (Figure 7B). The binding of HIF-1α to cad promoter was significantly increased by DFO treatment by as early as 4 h, and it remained so for up to 24 h (Figure 7B). In IMR32 neuroblastoma cells, basal binding of HIF-1α to cad promoter under normoxia was greater, but DFO treatment also increased the binding (Figure 7B).\n\nDISCUSSION\nHypoxic stress inhibits de novo biosynthesis of pyrimidine nucleotides, thus leading to cell-cycle arrest due to an insufficient supply of building materials for DNA synthesis (7). Nevertheless, how hypoxia causes reduction in pyrimidine biosynthesis remains enigmatic. The present study provides evidence demonstrating that HIF-1α transcriptionally inhibits the cad gene, which encodes a multifunctional enzyme that controls the rate-limiting step of pyrimidine biosynthesis (15,16). This conclusion is based on results obtained in experiments in which CAD expression declined in response to an increase in cellular levels of HIF-1α. A functional HRE was identified in human cad promoter, which was bound by HIF-1α as demonstrated by the ChIP assay. The use of dominant-negative form HIF-1α totally abolished the hypoxic effect provided further evidence to show the pivotal role of HIF-1α in suppressing cad-promoter activity. Furthermore, increasing HIF-1α levels in colo320DM, HeLa, A293T, IMR32 and primary endometrial stromal cells significantly inhibited cad expression, which unequivocally proved that repression of cad-promoter activity by HIF-1α is common in hypoxic cells. Taken together, our current data provide evidence to support that hypoxia-induced cell-cycle arrest might be the result of the inhibition of CAD expression by HIF-1α.\nDNA synthesis diminishes when oxygen is reduced from cell culture (27), which ultimately leads to cell-cycle arrest at the G1/S-phase. Previous studies focused on two oxygen-dependent enzymes, ribonucleotide reductase and dihydroorotate dehydrogenase. They concluded by hypothesizing that inactivation of these enzymes under hypoxia is the primary cause of a shortage of deoxynucleotide precursors for DNA replication and a consequent arrest of cell-cycle progression (28,29). However, these two enzymes work downstream of CAD, and other studies (15,16) suggest that the rate-limiting reaction of the entire pyrimidine synthesis is actually controlled at the step of converting glutamine to dihydroorotate, which involves three enzymatic activities possessed by CAD. In agreement with these reports, our results demonstrated that the expression of CAD is highly associated with the cell-cycle progression and the expression level of CAD truly reflects the proliferation rate of cells. The highest level of CAD expression in colo320DM cells occurred between 4 and 8 h after serum stimulation, which demonstrates CAD's functional role of providing nucleotides for DNA replication. Furthermore, we found that oxygen deprivation or increased cellular HIF-1α levels induced by DFO treatment significantly reduced the levels of CAD transcripts in colo320DM, HeLa, A293T, IMR32 and human endometrial stromal cells. These results not only demonstrate hypoxia-down-regulated CAD expression is a common phenomenon but also provide evidence to support the notion that hypoxia-induced cell-cycle arrest is directly related to the shortage of deoxynucleotide precursors for DNA synthesis (1).\nThe expression of hypoxia-responsive genes is primarily regulated by HIF-1α/HIF-1β transcription factor. The HIF heterodimer binds to a specific DNA-binding element, the HRE matrix, which contains a core sequence (5′-RCGTG-3′)and uncharacterized flanking sequences in the promoter region or other untranslated regions (30,31). Owing to the shortness of the sequence, the core HREs were observed frequently in the target-gene promoter, but only a few of them are effective for hypoxia-regulated gene expression. Cumulative data have demonstrated that the core HRE is necessary but not sufficient to regulate hypoxia-responsive genes (25,32,33). By using bioinformatic methodology, we identified one such HRE matrix in the proximal region of human cad promoter (−67/−54) and confirmed that this HRE matrix is important in HIF-1α-regulated cad-promoter activity by providing several lines of evidence. First, the promoter activity of the intact human cad promoter (−710/+122) was down-regulated under hypoxic condition or an increase in nuclear HIF-1α concentrations caused by DFO treatment. Second, the 25 bps human cad HRE matrix-containing plasmid responded to hypoxic stress exactly as that of intact cad promoter. Third, effect of hypoxia on cad-promoter activity was abrogated when the 25 bp HRE was mutated or by forced overexpression of dominant-negative HIF-1α. Fourth, physical binding of HIF-1α to the cad promoter was demonstrated by ChIP assay and the amounts of cad promoter-bound HIF-1α was significantly increased under hypoxic conditions.\nThe repression of cad-promoter activity by HIF-1α concurs with the notion that hypoxia causes a halt of pyrimidine nucleotide biosynthesis and that HIF-1α is indispensable for hypoxia-induced cell-cycle arrest (4). However, the in-depth mechanism responsible for inhibiting HIF-1-mediated cad-gene expression is not completely elucidated. The proximal cad promoter contains an E-box essential for c-Myc-induced CAD expression (34). It has been reported that HIF-1α can counteract c-Myc's function independent of HIF-1α's transcriptional activity and DNA-binding ability (35). In the current study, by showing that dominant-negative HIF-1α blocked the effects of hypoxia, we found that the binding of HIF-1α to the HRE matrix and retention of transcriptional capability are necessary for suppression of cad-promoter activity. Alternatively, it was reported that ATP-dependent hSWI/SNF chromatin remodeling complex containing mSin3A/histone deacetylase 2 (HDAC2) co-repressor might also be involved in the transcriptional repression of the cad gene (36). It is possible that the binding of HIF-1α to the HRE matrix recruits histone modification complex or other co-repressors to cad promoter and thus suppresses gene transcription. Further investigations on the nature of the partners of HIF-1 involved in cad down-regulation are crucial to elucidate the mechanisms involved in the repression of HIF-1-dependent hypoxia down-regulated genes.\nIn summary, we have demonstrated for the first time that HIF-1α transcriptionally suppressed cad-gene expression under hypoxia. This effect was unequivocally observed in four cancerous and non-cancerous cell lines and one primary culture cell type, which demonstrated that it is a common phenomenon. Given the critical role of CAD in nucleotides biosynthesis and consequent DNA replication, our data provide a functional link between hypoxia and cell-cycle arrest. Further investigation is warranted to explore effects of CAD suppression on the upregulation of checkpoint proteins and cell-cycle arrest when cells are under hypoxic stress, which may provide valuable information in designing novel regimens for treating hypoxia-related diseases. ","divisions":[{"label":"Title","span":{"begin":0,"end":76}},{"label":"Abstract","span":{"begin":87,"end":1355}},{"label":"Body","span":{"begin":1356,"end":29839}},{"label":"Section","span":{"begin":1356,"end":6307}},{"label":"Title","span":{"begin":1356,"end":1368}},{"label":"Section","span":{"begin":6309,"end":13995}},{"label":"Title","span":{"begin":6309,"end":6330}},{"label":"Section","span":{"begin":6332,"end":7113}},{"label":"Title","span":{"begin":6332,"end":6366}},{"label":"Section","span":{"begin":7115,"end":8304}},{"label":"Title","span":{"begin":7115,"end":7149}},{"label":"Section","span":{"begin":8306,"end":10125}},{"label":"Title","span":{"begin":8306,"end":8358}},{"label":"Section","span":{"begin":10127,"end":10879}},{"label":"Title","span":{"begin":10127,"end":10132}},{"label":"Section","span":{"begin":10881,"end":13521}},{"label":"Title","span":{"begin":10881,"end":10927}},{"label":"Section","span":{"begin":13523,"end":13994}},{"label":"Title","span":{"begin":13523,"end":13543}},{"label":"Section","span":{"begin":13996,"end":23058}},{"label":"Title","span":{"begin":13996,"end":14003}},{"label":"Section","span":{"begin":14005,"end":15178}},{"label":"Title","span":{"begin":14005,"end":14046}},{"label":"Section","span":{"begin":15180,"end":16694}},{"label":"Title","span":{"begin":15180,"end":15223}},{"label":"Section","span":{"begin":16696,"end":17888}},{"label":"Title","span":{"begin":16696,"end":16748}},{"label":"Section","span":{"begin":17890,"end":21209}},{"label":"Title","span":{"begin":17890,"end":17949}},{"label":"Section","span":{"begin":21211,"end":22006}},{"label":"Title","span":{"begin":21211,"end":21279}},{"label":"Section","span":{"begin":22008,"end":23057}},{"label":"Title","span":{"begin":22008,"end":22049}},{"label":"Section","span":{"begin":23059,"end":29838}},{"label":"Title","span":{"begin":23059,"end":23069}}],"tracks":[{"project":"Biotea","denotations":[{"id":"T8","span":{"begin":496,"end":501},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T5","span":{"begin":496,"end":501},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C14225"},{"id":"T6","span":{"begin":678,"end":683},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C14225"},{"id":"T9","span":{"begin":678,"end":683},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T11","span":{"begin":496,"end":501},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T12","span":{"begin":678,"end":683},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T14","span":{"begin":496,"end":501},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T15","span":{"begin":678,"end":683},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T17","span":{"begin":496,"end":501},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T18","span":{"begin":678,"end":683},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T20","span":{"begin":496,"end":501},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T21","span":{"begin":678,"end":683},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T23","span":{"begin":496,"end":501},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T24","span":{"begin":678,"end":683},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T26","span":{"begin":496,"end":501},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T27","span":{"begin":678,"end":683},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T29","span":{"begin":496,"end":501},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T30","span":{"begin":678,"end":683},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T32","span":{"begin":496,"end":501},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T33","span":{"begin":678,"end":683},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T35","span":{"begin":496,"end":501},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},{"id":"T36","span":{"begin":678,"end":683},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},{"id":"T38","span":{"begin":496,"end":501},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},{"id":"T39","span":{"begin":678,"end":683},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},{"id":"T42","span":{"begin":314,"end":317},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C38926"},{"id":"T43","span":{"begin":426,"end":429},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C38926"},{"id":"T44","span":{"begin":684,"end":687},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C38926"},{"id":"T45","span":{"begin":791,"end":794},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C38926"},{"id":"T46","span":{"begin":953,"end":956},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C38926"},{"id":"T47","span":{"begin":1183,"end":1186},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C38926"},{"id":"T48","span":{"begin":1237,"end":1240},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C38926"},{"id":"T50","span":{"begin":314,"end":317},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C10271"},{"id":"T51","span":{"begin":426,"end":429},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C10271"},{"id":"T52","span":{"begin":684,"end":687},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C10271"},{"id":"T53","span":{"begin":791,"end":794},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C10271"},{"id":"T54","span":{"begin":953,"end":956},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C10271"},{"id":"T55","span":{"begin":1183,"end":1186},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C10271"},{"id":"T56","span":{"begin":1237,"end":1240},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C10271"},{"id":"T58","span":{"begin":314,"end":317},"obj":"http://purl.obolibrary.org/obo/PR_O54788"},{"id":"T59","span":{"begin":426,"end":429},"obj":"http://purl.obolibrary.org/obo/PR_O54788"},{"id":"T60","span":{"begin":684,"end":687},"obj":"http://purl.obolibrary.org/obo/PR_O54788"},{"id":"T61","span":{"begin":791,"end":794},"obj":"http://purl.obolibrary.org/obo/PR_O54788"},{"id":"T62","span":{"begin":953,"end":956},"obj":"http://purl.obolibrary.org/obo/PR_O54788"},{"id":"T63","span":{"begin":1183,"end":1186},"obj":"http://purl.obolibrary.org/obo/PR_O54788"},{"id":"T64","span":{"begin":1237,"end":1240},"obj":"http://purl.obolibrary.org/obo/PR_O54788"},{"id":"T66","span":{"begin":314,"end":317},"obj":"http://purl.obolibrary.org/obo/PR_P12957"},{"id":"T67","span":{"begin":426,"end":429},"obj":"http://purl.obolibrary.org/obo/PR_P12957"},{"id":"T68","span":{"begin":684,"end":687},"obj":"http://purl.obolibrary.org/obo/PR_P12957"},{"id":"T69","span":{"begin":791,"end":794},"obj":"http://purl.obolibrary.org/obo/PR_P12957"},{"id":"T70","span":{"begin":953,"end":956},"obj":"http://purl.obolibrary.org/obo/PR_P12957"},{"id":"T71","span":{"begin":1183,"end":1186},"obj":"http://purl.obolibrary.org/obo/PR_P12957"},{"id":"T72","span":{"begin":1237,"end":1240},"obj":"http://purl.obolibrary.org/obo/PR_P12957"},{"id":"T74","span":{"begin":314,"end":317},"obj":"http://purl.obolibrary.org/obo/PR_000004974"},{"id":"T75","span":{"begin":426,"end":429},"obj":"http://purl.obolibrary.org/obo/PR_000004974"},{"id":"T76","span":{"begin":684,"end":687},"obj":"http://purl.obolibrary.org/obo/PR_000004974"},{"id":"T77","span":{"begin":791,"end":794},"obj":"http://purl.obolibrary.org/obo/PR_000004974"},{"id":"T78","span":{"begin":953,"end":956},"obj":"http://purl.obolibrary.org/obo/PR_000004974"},{"id":"T79","span":{"begin":1183,"end":1186},"obj":"http://purl.obolibrary.org/obo/PR_000004974"},{"id":"T80","span":{"begin":1237,"end":1240},"obj":"http://purl.obolibrary.org/obo/PR_000004974"},{"id":"T82","span":{"begin":314,"end":317},"obj":"http://purl.obolibrary.org/obo/PR_P48523"},{"id":"T83","span":{"begin":426,"end":429},"obj":"http://purl.obolibrary.org/obo/PR_P48523"},{"id":"T84","span":{"begin":684,"end":687},"obj":"http://purl.obolibrary.org/obo/PR_P48523"},{"id":"T85","span":{"begin":791,"end":794},"obj":"http://purl.obolibrary.org/obo/PR_P48523"},{"id":"T86","span":{"begin":953,"end":956},"obj":"http://purl.obolibrary.org/obo/PR_P48523"},{"id":"T87","span":{"begin":1183,"end":1186},"obj":"http://purl.obolibrary.org/obo/PR_P48523"},{"id":"T88","span":{"begin":1237,"end":1240},"obj":"http://purl.obolibrary.org/obo/PR_P48523"},{"id":"T90","span":{"begin":314,"end":317},"obj":"http://purl.obolibrary.org/obo/PR_P54987"},{"id":"T91","span":{"begin":426,"end":429},"obj":"http://purl.obolibrary.org/obo/PR_P54987"},{"id":"T92","span":{"begin":684,"end":687},"obj":"http://purl.obolibrary.org/obo/PR_P54987"},{"id":"T93","span":{"begin":791,"end":794},"obj":"http://purl.obolibrary.org/obo/PR_P54987"},{"id":"T94","span":{"begin":953,"end":956},"obj":"http://purl.obolibrary.org/obo/PR_P54987"},{"id":"T95","span":{"begin":1183,"end":1186},"obj":"http://purl.obolibrary.org/obo/PR_P54987"},{"id":"T96","span":{"begin":1237,"end":1240},"obj":"http://purl.obolibrary.org/obo/PR_P54987"},{"id":"T98","span":{"begin":314,"end":317},"obj":"http://purl.bioontology.org/ontology/MEDLINEPLUS/C1956346"},{"id":"T99","span":{"begin":426,"end":429},"obj":"http://purl.bioontology.org/ontology/MEDLINEPLUS/C1956346"},{"id":"T100","span":{"begin":684,"end":687},"obj":"http://purl.bioontology.org/ontology/MEDLINEPLUS/C1956346"},{"id":"T101","span":{"begin":791,"end":794},"obj":"http://purl.bioontology.org/ontology/MEDLINEPLUS/C1956346"},{"id":"T102","span":{"begin":953,"end":956},"obj":"http://purl.bioontology.org/ontology/MEDLINEPLUS/C1956346"},{"id":"T103","span":{"begin":1183,"end":1186},"obj":"http://purl.bioontology.org/ontology/MEDLINEPLUS/C1956346"},{"id":"T104","span":{"begin":1237,"end":1240},"obj":"http://purl.bioontology.org/ontology/MEDLINEPLUS/C1956346"},{"id":"T106","span":{"begin":314,"end":317},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C26732"},{"id":"T107","span":{"begin":426,"end":429},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C26732"},{"id":"T108","span":{"begin":684,"end":687},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C26732"},{"id":"T109","span":{"begin":791,"end":794},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C26732"},{"id":"T110","span":{"begin":953,"end":956},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C26732"},{"id":"T111","span":{"begin":1183,"end":1186},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C26732"},{"id":"T112","span":{"begin":1237,"end":1240},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C26732"},{"id":"T114","span":{"begin":314,"end":317},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113325"},{"id":"T115","span":{"begin":426,"end":429},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113325"},{"id":"T116","span":{"begin":684,"end":687},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113325"},{"id":"T117","span":{"begin":791,"end":794},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113325"},{"id":"T118","span":{"begin":953,"end":956},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113325"},{"id":"T119","span":{"begin":1183,"end":1186},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113325"},{"id":"T120","span":{"begin":1237,"end":1240},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113325"},{"id":"T122","span":{"begin":314,"end":317},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C153871"},{"id":"T123","span":{"begin":426,"end":429},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C153871"},{"id":"T124","span":{"begin":684,"end":687},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C153871"},{"id":"T125","span":{"begin":791,"end":794},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C153871"},{"id":"T126","span":{"begin":953,"end":956},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C153871"},{"id":"T127","span":{"begin":1183,"end":1186},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C153871"},{"id":"T128","span":{"begin":1237,"end":1240},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C153871"},{"id":"T130","span":{"begin":314,"end":317},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126527"},{"id":"T131","span":{"begin":426,"end":429},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126527"},{"id":"T132","span":{"begin":684,"end":687},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126527"},{"id":"T133","span":{"begin":791,"end":794},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126527"},{"id":"T134","span":{"begin":953,"end":956},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126527"},{"id":"T135","span":{"begin":1183,"end":1186},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126527"},{"id":"T136","span":{"begin":1237,"end":1240},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126527"},{"id":"T138","span":{"begin":314,"end":317},"obj":"http://purl.obolibrary.org/obo/PR_Q99N34"},{"id":"T139","span":{"begin":426,"end":429},"obj":"http://purl.obolibrary.org/obo/PR_Q99N34"},{"id":"T140","span":{"begin":684,"end":687},"obj":"http://purl.obolibrary.org/obo/PR_Q99N34"},{"id":"T141","span":{"begin":791,"end":794},"obj":"http://purl.obolibrary.org/obo/PR_Q99N34"},{"id":"T142","span":{"begin":953,"end":956},"obj":"http://purl.obolibrary.org/obo/PR_Q99N34"},{"id":"T143","span":{"begin":1183,"end":1186},"obj":"http://purl.obolibrary.org/obo/PR_Q99N34"},{"id":"T144","span":{"begin":1237,"end":1240},"obj":"http://purl.obolibrary.org/obo/PR_Q99N34"},{"id":"T146","span":{"begin":314,"end":317},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C63604"},{"id":"T147","span":{"begin":426,"end":429},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C63604"},{"id":"T148","span":{"begin":684,"end":687},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C63604"},{"id":"T149","span":{"begin":791,"end":794},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C63604"},{"id":"T150","span":{"begin":953,"end":956},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C63604"},{"id":"T151","span":{"begin":1183,"end":1186},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C63604"},{"id":"T152","span":{"begin":1237,"end":1240},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C63604"},{"id":"T154","span":{"begin":314,"end":317},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C9697"},{"id":"T155","span":{"begin":426,"end":429},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C9697"},{"id":"T156","span":{"begin":684,"end":687},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C9697"},{"id":"T157","span":{"begin":791,"end":794},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C9697"},{"id":"T158","span":{"begin":953,"end":956},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C9697"},{"id":"T159","span":{"begin":1183,"end":1186},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C9697"},{"id":"T160","span":{"begin":1237,"end":1240},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C9697"},{"id":"T162","span":{"begin":314,"end":317},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126526"},{"id":"T163","span":{"begin":426,"end":429},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126526"},{"id":"T164","span":{"begin":684,"end":687},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126526"},{"id":"T165","span":{"begin":791,"end":794},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126526"},{"id":"T166","span":{"begin":953,"end":956},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126526"},{"id":"T167","span":{"begin":1183,"end":1186},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126526"},{"id":"T168","span":{"begin":1237,"end":1240},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126526"},{"id":"T170","span":{"begin":314,"end":317},"obj":"http://purl.obolibrary.org/obo/PR_000004959"},{"id":"T171","span":{"begin":426,"end":429},"obj":"http://purl.obolibrary.org/obo/PR_000004959"},{"id":"T172","span":{"begin":684,"end":687},"obj":"http://purl.obolibrary.org/obo/PR_000004959"},{"id":"T173","span":{"begin":791,"end":794},"obj":"http://purl.obolibrary.org/obo/PR_000004959"},{"id":"T174","span":{"begin":953,"end":956},"obj":"http://purl.obolibrary.org/obo/PR_000004959"},{"id":"T175","span":{"begin":1183,"end":1186},"obj":"http://purl.obolibrary.org/obo/PR_000004959"},{"id":"T176","span":{"begin":1237,"end":1240},"obj":"http://purl.obolibrary.org/obo/PR_000004959"},{"id":"T178","span":{"begin":314,"end":317},"obj":"http://purl.obolibrary.org/obo/PR_000006430"},{"id":"T179","span":{"begin":426,"end":429},"obj":"http://purl.obolibrary.org/obo/PR_000006430"},{"id":"T180","span":{"begin":684,"end":687},"obj":"http://purl.obolibrary.org/obo/PR_000006430"},{"id":"T181","span":{"begin":791,"end":794},"obj":"http://purl.obolibrary.org/obo/PR_000006430"},{"id":"T182","span":{"begin":953,"end":956},"obj":"http://purl.obolibrary.org/obo/PR_000006430"},{"id":"T183","span":{"begin":1183,"end":1186},"obj":"http://purl.obolibrary.org/obo/PR_000006430"},{"id":"T184","span":{"begin":1237,"end":1240},"obj":"http://purl.obolibrary.org/obo/PR_000006430"},{"id":"T186","span":{"begin":688,"end":692},"obj":"http://purl.org/sig/ont/fma/fma74402"},{"id":"T187","span":{"begin":907,"end":911},"obj":"http://purl.org/sig/ont/fma/fma74402"},{"id":"T188","span":{"begin":1241,"end":1245},"obj":"http://purl.org/sig/ont/fma/fma74402"},{"id":"T190","span":{"begin":688,"end":692},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/67271001"},{"id":"T191","span":{"begin":907,"end":911},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/67271001"},{"id":"T192","span":{"begin":1241,"end":1245},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/67271001"},{"id":"T194","span":{"begin":688,"end":692},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C45520"},{"id":"T195","span":{"begin":907,"end":911},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C45520"},{"id":"T196","span":{"begin":1241,"end":1245},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C45520"},{"id":"T198","span":{"begin":688,"end":692},"obj":"http://purl.obolibrary.org/obo/SO_0000704"},{"id":"T199","span":{"begin":907,"end":911},"obj":"http://purl.obolibrary.org/obo/SO_0000704"},{"id":"T200","span":{"begin":1241,"end":1245},"obj":"http://purl.obolibrary.org/obo/SO_0000704"},{"id":"T202","span":{"begin":688,"end":692},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16612"},{"id":"T203","span":{"begin":907,"end":911},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16612"},{"id":"T204","span":{"begin":1241,"end":1245},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16612"},{"id":"T206","span":{"begin":573,"end":576},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113839"},{"id":"T207","span":{"begin":1026,"end":1029},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113839"},{"id":"T208","span":{"begin":1086,"end":1089},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113839"},{"id":"T209","span":{"begin":1163,"end":1166},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113839"},{"id":"T210","span":{"begin":1273,"end":1276},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113839"},{"id":"T212","span":{"begin":532,"end":539},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C3890"},{"id":"T213","span":{"begin":605,"end":612},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C3890"},{"id":"T214","span":{"begin":929,"end":936},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C3890"},{"id":"T215","span":{"begin":1324,"end":1331},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C3890"},{"id":"T217","span":{"begin":532,"end":539},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/389086002"},{"id":"T218","span":{"begin":605,"end":612},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/389086002"},{"id":"T219","span":{"begin":929,"end":936},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/389086002"},{"id":"T220","span":{"begin":1324,"end":1331},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/389086002"},{"id":"T222","span":{"begin":532,"end":539},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C58188"},{"id":"T223","span":{"begin":605,"end":612},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C58188"},{"id":"T224","span":{"begin":929,"end":936},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C58188"},{"id":"T225","span":{"begin":1324,"end":1331},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C58188"},{"id":"T227","span":{"begin":532,"end":539},"obj":"http://purl.bioontology.org/ontology/NDFRT/N0000000426"},{"id":"T228","span":{"begin":605,"end":612},"obj":"http://purl.bioontology.org/ontology/NDFRT/N0000000426"},{"id":"T229","span":{"begin":929,"end":936},"obj":"http://purl.bioontology.org/ontology/NDFRT/N0000000426"},{"id":"T230","span":{"begin":1324,"end":1331},"obj":"http://purl.bioontology.org/ontology/NDFRT/N0000000426"},{"id":"T232","span":{"begin":532,"end":539},"obj":"http://purl.bioontology.org/ontology/OMIM/MTHU016005"},{"id":"T233","span":{"begin":605,"end":612},"obj":"http://purl.bioontology.org/ontology/OMIM/MTHU016005"},{"id":"T234","span":{"begin":929,"end":936},"obj":"http://purl.bioontology.org/ontology/OMIM/MTHU016005"},{"id":"T235","span":{"begin":1324,"end":1331},"obj":"http://purl.bioontology.org/ontology/OMIM/MTHU016005"},{"id":"T237","span":{"begin":532,"end":539},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10021143"},{"id":"T238","span":{"begin":605,"end":612},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10021143"},{"id":"T239","span":{"begin":929,"end":936},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10021143"},{"id":"T240","span":{"begin":1324,"end":1331},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10021143"},{"id":"T242","span":{"begin":532,"end":539},"obj":"http://purl.bioontology.org/ontology/MESH/D000860"},{"id":"T243","span":{"begin":605,"end":612},"obj":"http://purl.bioontology.org/ontology/MESH/D000860"},{"id":"T244","span":{"begin":929,"end":936},"obj":"http://purl.bioontology.org/ontology/MESH/D000860"},{"id":"T245","span":{"begin":1324,"end":1331},"obj":"http://purl.bioontology.org/ontology/MESH/D000860"},{"id":"T247","span":{"begin":565,"end":572},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C61367"},{"id":"T250","span":{"begin":87,"end":94},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C28354"},{"id":"T251","span":{"begin":231,"end":238},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C28354"},{"id":"T252","span":{"begin":95,"end":107},"obj":"http://purl.bioontology.org/ontology/MESH/Q000096"},{"id":"T253","span":{"begin":250,"end":262},"obj":"http://purl.bioontology.org/ontology/MESH/Q000096"},{"id":"T254","span":{"begin":95,"end":107},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C17702"},{"id":"T255","span":{"begin":250,"end":262},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C17702"},{"id":"T256","span":{"begin":95,"end":107},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T257","span":{"begin":172,"end":181},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T258","span":{"begin":250,"end":262},"obj":"http://purl.obolibrary.org/obo/GO_0009058"},{"id":"T259","span":{"begin":111,"end":133},"obj":"http://purl.bioontology.org/ontology/NDFRT/N0000170767"},{"id":"T260","span":{"begin":111,"end":133},"obj":"http://purl.bioontology.org/ontology/MESH/D011742"},{"id":"T261","span":{"begin":111,"end":121},"obj":"http://purl.bioontology.org/ontology/MESH/C030986"},{"id":"T262","span":{"begin":239,"end":249},"obj":"http://purl.bioontology.org/ontology/MESH/C030986"},{"id":"T263","span":{"begin":111,"end":121},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/7321000"},{"id":"T264","span":{"begin":239,"end":249},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/7321000"},{"id":"T265","span":{"begin":111,"end":121},"obj":"http://purl.org/sig/ont/fma/fma82773"},{"id":"T266","span":{"begin":239,"end":249},"obj":"http://purl.org/sig/ont/fma/fma82773"},{"id":"T267","span":{"begin":111,"end":121},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C789"},{"id":"T268","span":{"begin":239,"end":249},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C789"},{"id":"T269","span":{"begin":122,"end":133},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C709"},{"id":"T270","span":{"begin":122,"end":133},"obj":"http://purl.bioontology.org/ontology/MESH/D009711"},{"id":"T271","span":{"begin":122,"end":133},"obj":"http://purl.bioontology.org/ontology/NDFRT/N0000008236"},{"id":"T272","span":{"begin":143,"end":152},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C71578"},{"id":"T273","span":{"begin":143,"end":152},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/34325006"},{"id":"T274","span":{"begin":168,"end":181},"obj":"http://purl.obolibrary.org/obo/GO_0071897"},{"id":"T275","span":{"begin":168,"end":181},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C18125"},{"id":"T276","span":{"begin":168,"end":171},"obj":"http://purl.org/sig/ont/fma/fma74412"},{"id":"T277","span":{"begin":168,"end":171},"obj":"http://purl.obolibrary.org/obo/GO_0005574"},{"id":"T278","span":{"begin":168,"end":171},"obj":"http://purl.bioontology.org/ontology/MESH/D004247"},{"id":"T279","span":{"begin":168,"end":171},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C135409"},{"id":"T280","span":{"begin":168,"end":171},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C449"},{"id":"T281","span":{"begin":172,"end":181},"obj":"http://purl.obolibrary.org/obo/OBI_0600040"},{"id":"T282","span":{"begin":172,"end":181},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C61408"},{"id":"T283","span":{"begin":186,"end":204},"obj":"http://purl.bioontology.org/ontology/MESH/D049109"},{"id":"T284","span":{"begin":186,"end":204},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C18081"},{"id":"T285","span":{"begin":186,"end":204},"obj":"http://purl.obolibrary.org/obo/GO_0008283"},{"id":"T286","span":{"begin":186,"end":204},"obj":"http://purl.obolibrary.org/obo/GO_0008283"},{"id":"T287","span":{"begin":186,"end":204},"obj":"http://purl.obolibrary.org/obo/GO_0008283"},{"id":"T288","span":{"begin":186,"end":190},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T289","span":{"begin":465,"end":469},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T290","span":{"begin":1336,"end":1340},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T291","span":{"begin":186,"end":190},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T292","span":{"begin":465,"end":469},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T293","span":{"begin":1336,"end":1340},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T294","span":{"begin":186,"end":190},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T295","span":{"begin":465,"end":469},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T296","span":{"begin":1336,"end":1340},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T297","span":{"begin":186,"end":190},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T298","span":{"begin":465,"end":469},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T299","span":{"begin":1336,"end":1340},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T300","span":{"begin":186,"end":190},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T301","span":{"begin":465,"end":469},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T302","span":{"begin":1336,"end":1340},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T303","span":{"begin":186,"end":190},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T304","span":{"begin":465,"end":469},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T305","span":{"begin":1336,"end":1340},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T306","span":{"begin":186,"end":190},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T307","span":{"begin":465,"end":469},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T308","span":{"begin":1336,"end":1340},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T309","span":{"begin":186,"end":190},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T310","span":{"begin":465,"end":469},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T311","span":{"begin":1336,"end":1340},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T312","span":{"begin":186,"end":190},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T313","span":{"begin":465,"end":469},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T314","span":{"begin":1336,"end":1340},"obj":"http://purl.bioontology.org/ontology/STY/T025"},{"id":"T315","span":{"begin":186,"end":190},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C49867"},{"id":"T316","span":{"begin":465,"end":469},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C49867"},{"id":"T317","span":{"begin":1336,"end":1340},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C49867"},{"id":"T318","span":{"begin":186,"end":190},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T319","span":{"begin":465,"end":469},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T320","span":{"begin":1336,"end":1340},"obj":"http://purl.obolibrary.org/obo/GO_0005623"},{"id":"T321","span":{"begin":186,"end":190},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C12508"},{"id":"T322","span":{"begin":465,"end":469},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C12508"},{"id":"T323","span":{"begin":510,"end":515},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C12508"},{"id":"T324","span":{"begin":1336,"end":1340},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C12508"},{"id":"T325","span":{"begin":186,"end":190},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C23442"},{"id":"T326","span":{"begin":465,"end":469},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C23442"},{"id":"T327","span":{"begin":1336,"end":1340},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C23442"},{"id":"T328","span":{"begin":186,"end":190},"obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"T329","span":{"begin":465,"end":469},"obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"T330","span":{"begin":1336,"end":1340},"obj":"http://purl.org/sig/ont/fma/fma68646"},{"id":"T331","span":{"begin":186,"end":190},"obj":"http://purl.obolibrary.org/obo/CL_0000000"},{"id":"T332","span":{"begin":465,"end":469},"obj":"http://purl.obolibrary.org/obo/CL_0000000"},{"id":"T333","span":{"begin":1336,"end":1340},"obj":"http://purl.obolibrary.org/obo/CL_0000000"},{"id":"T334","span":{"begin":186,"end":190},"obj":"http://purl.obolibrary.org/obo/CL_0000000"},{"id":"T335","span":{"begin":465,"end":469},"obj":"http://purl.obolibrary.org/obo/CL_0000000"},{"id":"T336","span":{"begin":1336,"end":1340},"obj":"http://purl.obolibrary.org/obo/CL_0000000"},{"id":"T337","span":{"begin":186,"end":190},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C60787"},{"id":"T338","span":{"begin":465,"end":469},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C60787"},{"id":"T339","span":{"begin":1336,"end":1340},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C60787"},{"id":"T340","span":{"begin":186,"end":190},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C48694"},{"id":"T341","span":{"begin":465,"end":469},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C48694"},{"id":"T342","span":{"begin":1336,"end":1340},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C48694"},{"id":"T343","span":{"begin":186,"end":190},"obj":"http://purl.bioontology.org/ontology/MESH/D002477"},{"id":"T344","span":{"begin":465,"end":469},"obj":"http://purl.bioontology.org/ontology/MESH/D002477"},{"id":"T345","span":{"begin":510,"end":515},"obj":"http://purl.bioontology.org/ontology/MESH/D002477"},{"id":"T346","span":{"begin":1336,"end":1340},"obj":"http://purl.bioontology.org/ontology/MESH/D002477"},{"id":"T347","span":{"begin":191,"end":204},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C37897"},{"id":"T348","span":{"begin":191,"end":204},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C28378"},{"id":"T349","span":{"begin":191,"end":204},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/30217000"},{"id":"T350","span":{"begin":216,"end":221},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C66834"},{"id":"T351","span":{"begin":216,"end":221},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/79605009"},{"id":"T352","span":{"begin":222,"end":227},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C156404"},{"id":"T353","span":{"begin":222,"end":227},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C111318"},{"id":"T354","span":{"begin":298,"end":304},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16554"},{"id":"T355","span":{"begin":298,"end":304},"obj":"http://purl.obolibrary.org/obo/OBI_0000427"},{"id":"T356","span":{"begin":298,"end":304},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/90668006"},{"id":"T357","span":{"begin":298,"end":304},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/734543001"},{"id":"T358","span":{"begin":298,"end":304},"obj":"http://purl.bioontology.org/ontology/STY/T126"},{"id":"T359","span":{"begin":298,"end":304},"obj":"http://purl.bioontology.org/ontology/STY/T126"},{"id":"T360","span":{"begin":298,"end":304},"obj":"http://purl.bioontology.org/ontology/STY/T126"},{"id":"T361","span":{"begin":298,"end":304},"obj":"http://purl.bioontology.org/ontology/STY/T126"},{"id":"T362","span":{"begin":298,"end":304},"obj":"http://purl.bioontology.org/ontology/STY/T126"},{"id":"T363","span":{"begin":298,"end":304},"obj":"http://purl.bioontology.org/ontology/STY/T126"},{"id":"T364","span":{"begin":298,"end":304},"obj":"http://purl.bioontology.org/ontology/STY/T126"},{"id":"T365","span":{"begin":298,"end":304},"obj":"http://purl.bioontology.org/ontology/STY/T126"},{"id":"T366","span":{"begin":298,"end":304},"obj":"http://purl.bioontology.org/ontology/STY/T126"},{"id":"T367","span":{"begin":329,"end":338},"obj":"http://purl.bioontology.org/ontology/NDFRT/N0000022459"},{"id":"T368","span":{"begin":329,"end":338},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10034928"},{"id":"T369","span":{"begin":329,"end":338},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C64857"},{"id":"T370","span":{"begin":329,"end":338},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/259296007"},{"id":"T371","span":{"begin":329,"end":338},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C94713"},{"id":"T372","span":{"begin":339,"end":349},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/736223009"},{"id":"T373","span":{"begin":350,"end":380},"obj":"http://purl.bioontology.org/ontology/MESH/D001221"},{"id":"T374","span":{"begin":350,"end":380},"obj":"http://purl.bioontology.org/ontology/NDFRT/N0000168168"},{"id":"T375","span":{"begin":350,"end":380},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/18786009"},{"id":"T376","span":{"begin":350,"end":359},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C122097"},{"id":"T377","span":{"begin":350,"end":359},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/430504000"},{"id":"T378","span":{"begin":381,"end":395},"obj":"http://purl.obolibrary.org/obo/PR_000044418"},{"id":"T379","span":{"begin":381,"end":395},"obj":"http://purl.bioontology.org/ontology/MESH/D004080"},{"id":"T380","span":{"begin":381,"end":395},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/78556003"},{"id":"T381","span":{"begin":406,"end":410},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C74299"},{"id":"T382","span":{"begin":406,"end":410},"obj":"http://purl.bioontology.org/ontology/MESH/D014937"},{"id":"T383","span":{"begin":414,"end":422},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C25640"},{"id":"T384","span":{"begin":414,"end":422},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/260370003"},{"id":"T385","span":{"begin":430,"end":440},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C80488"},{"id":"T386","span":{"begin":912,"end":922},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C80488"},{"id":"T387","span":{"begin":1002,"end":1012},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C80488"},{"id":"T388","span":{"begin":1246,"end":1256},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C80488"},{"id":"T389","span":{"begin":430,"end":440},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/706999006"},{"id":"T390","span":{"begin":912,"end":922},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/706999006"},{"id":"T391","span":{"begin":1002,"end":1012},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/706999006"},{"id":"T392","span":{"begin":1246,"end":1256},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/706999006"},{"id":"T393","span":{"begin":430,"end":440},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16608"},{"id":"T394","span":{"begin":907,"end":922},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16608"},{"id":"T395","span":{"begin":912,"end":922},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16608"},{"id":"T396","span":{"begin":1002,"end":1012},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16608"},{"id":"T397","span":{"begin":1241,"end":1256},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16608"},{"id":"T398","span":{"begin":1246,"end":1256},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16608"},{"id":"T399","span":{"begin":430,"end":440},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/10012005"},{"id":"T400","span":{"begin":912,"end":922},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/10012005"},{"id":"T401","span":{"begin":1002,"end":1012},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/10012005"},{"id":"T402","span":{"begin":1246,"end":1256},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/10012005"},{"id":"T403","span":{"begin":444,"end":452},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C25481"},{"id":"T404","span":{"begin":444,"end":452},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16210"},{"id":"T405","span":{"begin":444,"end":452},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/260373001"},{"id":"T406","span":{"begin":456,"end":464},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/260396001"},{"id":"T407","span":{"begin":465,"end":475},"obj":"http://purl.bioontology.org/ontology/MESH/D002460"},{"id":"T408","span":{"begin":470,"end":475},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C13803"},{"id":"T409","span":{"begin":480,"end":487},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C25251"},{"id":"T410","span":{"begin":488,"end":495},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C45415"},{"id":"T411","span":{"begin":488,"end":495},"obj":"http://purl.bioontology.org/ontology/MESH/D003469"},{"id":"T412","span":{"begin":488,"end":495},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/703725008"},{"id":"T413","span":{"begin":488,"end":495},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16478"},{"id":"T414","span":{"begin":488,"end":495},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10061447"},{"id":"T415","span":{"begin":488,"end":495},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C25300"},{"id":"T416","span":{"begin":488,"end":495},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/61594008"},{"id":"T417","span":{"begin":502,"end":515},"obj":"http://purl.bioontology.org/ontology/MESH/D017154"},{"id":"T418","span":{"begin":502,"end":515},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C12571"},{"id":"T419","span":{"begin":502,"end":515},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C23505"},{"id":"T420","span":{"begin":510,"end":515},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C48938"},{"id":"T421","span":{"begin":510,"end":515},"obj":"http://purl.bioontology.org/ontology/NDFRT/N0000184307"},{"id":"T422","span":{"begin":516,"end":525},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C15685"},{"id":"T423","span":{"begin":543,"end":558},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C416"},{"id":"T424","span":{"begin":543,"end":558},"obj":"http://purl.bioontology.org/ontology/NDFRT/N0000007065"},{"id":"T425","span":{"begin":543,"end":558},"obj":"http://purl.bioontology.org/ontology/MESH/D003676"},{"id":"T426","span":{"begin":543,"end":558},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/372825006"},{"id":"T427","span":{"begin":565,"end":572},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/16404004"},{"id":"T428","span":{"begin":580,"end":592},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C120860"},{"id":"T429","span":{"begin":613,"end":629},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C13372"},{"id":"T430","span":{"begin":613,"end":621},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C25755"},{"id":"T431","span":{"begin":613,"end":621},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C50995"},{"id":"T432","span":{"begin":613,"end":621},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C49149"},{"id":"T433","span":{"begin":613,"end":621},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C82658"},{"id":"T434","span":{"begin":622,"end":629},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C105752"},{"id":"T435","span":{"begin":622,"end":629},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C48792"},{"id":"T436","span":{"begin":622,"end":629},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C1940"},{"id":"T437","span":{"begin":622,"end":629},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/57795002"},{"id":"T438","span":{"begin":636,"end":643},"obj":"http://purl.obolibrary.org/obo/GO_0005488"},{"id":"T439","span":{"begin":636,"end":643},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/257768005"},{"id":"T440","span":{"begin":636,"end":643},"obj":"http://purl.obolibrary.org/obo/OBI_0001588"},{"id":"T441","span":{"begin":636,"end":643},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C82888"},{"id":"T442","span":{"begin":636,"end":643},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C18219"},{"id":"T443","span":{"begin":644,"end":650},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/733002003"},{"id":"T444","span":{"begin":644,"end":650},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C140106"},{"id":"T445","span":{"begin":644,"end":650},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C45802"},{"id":"T446","span":{"begin":644,"end":650},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C149645"},{"id":"T447","span":{"begin":644,"end":650},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C45805"},{"id":"T448","span":{"begin":654,"end":664},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/7882003"},{"id":"T449","span":{"begin":654,"end":664},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C25737"},{"id":"T450","span":{"begin":693,"end":701},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C13297"},{"id":"T451","span":{"begin":734,"end":742},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C13297"},{"id":"T452","span":{"begin":795,"end":803},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C13297"},{"id":"T453","span":{"begin":957,"end":965},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C13297"},{"id":"T454","span":{"begin":1187,"end":1195},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C13297"},{"id":"T455","span":{"begin":743,"end":751},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C43431"},{"id":"T456","span":{"begin":966,"end":974},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C43431"},{"id":"T457","span":{"begin":743,"end":751},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C120914"},{"id":"T458","span":{"begin":966,"end":974},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C120914"},{"id":"T459","span":{"begin":743,"end":751},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T460","span":{"begin":966,"end":974},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T461","span":{"begin":743,"end":751},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T462","span":{"begin":966,"end":974},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T463","span":{"begin":743,"end":751},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T464","span":{"begin":966,"end":974},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T465","span":{"begin":743,"end":751},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T466","span":{"begin":966,"end":974},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T467","span":{"begin":743,"end":751},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T468","span":{"begin":966,"end":974},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T469","span":{"begin":743,"end":751},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T470","span":{"begin":966,"end":974},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T471","span":{"begin":743,"end":751},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T472","span":{"begin":966,"end":974},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T473","span":{"begin":743,"end":751},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T474","span":{"begin":966,"end":974},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T475","span":{"begin":743,"end":751},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T476","span":{"begin":966,"end":974},"obj":"http://purl.bioontology.org/ontology/STY/T052"},{"id":"T477","span":{"begin":743,"end":751},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C123268"},{"id":"T478","span":{"begin":966,"end":974},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C123268"},{"id":"T479","span":{"begin":743,"end":751},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C45329"},{"id":"T480","span":{"begin":966,"end":974},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C45329"},{"id":"T481","span":{"begin":743,"end":751},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/257733005"},{"id":"T482","span":{"begin":966,"end":974},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/257733005"},{"id":"T483","span":{"begin":832,"end":840},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C48295"},{"id":"T484","span":{"begin":832,"end":840},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C124536"},{"id":"T485","span":{"begin":883,"end":894},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/80633008"},{"id":"T486","span":{"begin":938,"end":949},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/80633008"},{"id":"T487","span":{"begin":898,"end":906},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C41191"},{"id":"T488","span":{"begin":898,"end":906},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C44255"},{"id":"T489","span":{"begin":898,"end":906},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/51764002"},{"id":"T490","span":{"begin":898,"end":906},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C53461"},{"id":"T491","span":{"begin":898,"end":906},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C2480"},{"id":"T492","span":{"begin":907,"end":922},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C21049"},{"id":"T493","span":{"begin":1241,"end":1256},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C21049"},{"id":"T494","span":{"begin":907,"end":922},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C135484"},{"id":"T495","span":{"begin":1241,"end":1256},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C135484"},{"id":"T496","span":{"begin":907,"end":922},"obj":"http://purl.bioontology.org/ontology/MESH/D015870"},{"id":"T497","span":{"begin":1241,"end":1256},"obj":"http://purl.bioontology.org/ontology/MESH/D015870"},{"id":"T498","span":{"begin":907,"end":922},"obj":"http://purl.obolibrary.org/obo/GO_0010467"},{"id":"T499","span":{"begin":1241,"end":1256},"obj":"http://purl.obolibrary.org/obo/GO_0010467"},{"id":"T500","span":{"begin":907,"end":922},"obj":"http://purl.obolibrary.org/obo/GO_0010467"},{"id":"T501","span":{"begin":1241,"end":1256},"obj":"http://purl.obolibrary.org/obo/GO_0010467"},{"id":"T502","span":{"begin":907,"end":922},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/89551006"},{"id":"T503","span":{"begin":1241,"end":1256},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/89551006"},{"id":"T504","span":{"begin":995,"end":1001},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C87139"},{"id":"T505","span":{"begin":995,"end":1001},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C48161"},{"id":"T506","span":{"begin":995,"end":1001},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/263760002"},{"id":"T507","span":{"begin":1016,"end":1020},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/262290003"},{"id":"T508","span":{"begin":1021,"end":1025},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/410656007"},{"id":"T509","span":{"begin":1021,"end":1025},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C25284"},{"id":"T510","span":{"begin":1050,"end":1064},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C18211"},{"id":"T511","span":{"begin":1068,"end":1076},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C25487"},{"id":"T512","span":{"begin":1077,"end":1085},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C38757"},{"id":"T513","span":{"begin":1077,"end":1085},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C81022"},{"id":"T514","span":{"begin":1077,"end":1085},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/260385009"},{"id":"T515","span":{"begin":1077,"end":1085},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C81173"},{"id":"T516","span":{"begin":1077,"end":1085},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C25247"},{"id":"T517","span":{"begin":1096,"end":1131},"obj":"http://purl.obolibrary.org/obo/OBI_0001954"},{"id":"T518","span":{"begin":1096,"end":1125},"obj":"http://purl.bioontology.org/ontology/MESH/D047369"},{"id":"T519","span":{"begin":1096,"end":1125},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C106048"},{"id":"T520","span":{"begin":1096,"end":1125},"obj":"http://purl.obolibrary.org/obo/OBI_00001975"},{"id":"T521","span":{"begin":1096,"end":1105},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/60085001"},{"id":"T522","span":{"begin":1096,"end":1105},"obj":"http://purl.obolibrary.org/obo/GO_0000785"},{"id":"T523","span":{"begin":1096,"end":1105},"obj":"http://purl.obolibrary.org/obo/GO_0000785"},{"id":"T524","span":{"begin":1096,"end":1105},"obj":"http://purl.bioontology.org/ontology/MESH/D002843"},{"id":"T525","span":{"begin":1096,"end":1105},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C13201"},{"id":"T526","span":{"begin":1096,"end":1105},"obj":"http://purl.org/sig/ont/fma/fma67526"},{"id":"T527","span":{"begin":1096,"end":1105},"obj":"http://purl.bioontology.org/ontology/NDFRT/N0000169072"},{"id":"T528","span":{"begin":1106,"end":1131},"obj":"http://purl.obolibrary.org/obo/OBI_0001700"},{"id":"T529","span":{"begin":1106,"end":1125},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16724"},{"id":"T530","span":{"begin":1106,"end":1125},"obj":"http://purl.obolibrary.org/obo/OBI_0000690"},{"id":"T531","span":{"begin":1106,"end":1125},"obj":"http://purl.bioontology.org/ontology/MESH/D047468"},{"id":"T532","span":{"begin":1126,"end":1131},"obj":"http://purl.obolibrary.org/obo/OBI_0000070"},{"id":"T533","span":{"begin":1126,"end":1131},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16341"},{"id":"T534","span":{"begin":1126,"end":1131},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C60819"},{"id":"T535","span":{"begin":1126,"end":1131},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/272392009"},{"id":"T536","span":{"begin":1149,"end":1157},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C43583"},{"id":"T537","span":{"begin":1196,"end":1203},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C15744"},{"id":"T538","span":{"begin":1300,"end":1310},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C75924"},{"id":"T539","span":{"begin":1300,"end":1310},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/40143009"},{"id":"T540","span":{"begin":1300,"end":1310},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C25518"},{"id":"T541","span":{"begin":1311,"end":1315},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C19470"},{"id":"T542","span":{"begin":1311,"end":1315},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C47919"},{"id":"T543","span":{"begin":1341,"end":1346},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C25472"},{"id":"T544","span":{"begin":1347,"end":1353},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C61462"},{"id":"T1","span":{"begin":0,"end":26},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16521"},{"id":"T2","span":{"begin":0,"end":15},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C17208"},{"id":"T3","span":{"begin":16,"end":26},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C17086"},{"id":"T4","span":{"begin":30,"end":35},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C14225"},{"id":"T7","span":{"begin":30,"end":35},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T10","span":{"begin":30,"end":35},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T13","span":{"begin":30,"end":35},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T16","span":{"begin":30,"end":35},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T19","span":{"begin":30,"end":35},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T22","span":{"begin":30,"end":35},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T25","span":{"begin":30,"end":35},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T28","span":{"begin":30,"end":35},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T31","span":{"begin":30,"end":35},"obj":"http://purl.bioontology.org/ontology/STY/T016"},{"id":"T34","span":{"begin":30,"end":35},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},{"id":"T37","span":{"begin":30,"end":35},"obj":"http://purl.obolibrary.org/obo/NCBITaxon_9606"},{"id":"T40","span":{"begin":36,"end":44},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C38926"},{"id":"T41","span":{"begin":36,"end":39},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C38926"},{"id":"T49","span":{"begin":36,"end":39},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C10271"},{"id":"T57","span":{"begin":36,"end":39},"obj":"http://purl.obolibrary.org/obo/PR_O54788"},{"id":"T65","span":{"begin":36,"end":39},"obj":"http://purl.obolibrary.org/obo/PR_P12957"},{"id":"T73","span":{"begin":36,"end":39},"obj":"http://purl.obolibrary.org/obo/PR_000004974"},{"id":"T81","span":{"begin":36,"end":39},"obj":"http://purl.obolibrary.org/obo/PR_P48523"},{"id":"T89","span":{"begin":36,"end":39},"obj":"http://purl.obolibrary.org/obo/PR_P54987"},{"id":"T97","span":{"begin":36,"end":39},"obj":"http://purl.bioontology.org/ontology/MEDLINEPLUS/C1956346"},{"id":"T105","span":{"begin":36,"end":39},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C26732"},{"id":"T113","span":{"begin":36,"end":39},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113325"},{"id":"T121","span":{"begin":36,"end":39},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C153871"},{"id":"T129","span":{"begin":36,"end":39},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126527"},{"id":"T137","span":{"begin":36,"end":39},"obj":"http://purl.obolibrary.org/obo/PR_Q99N34"},{"id":"T145","span":{"begin":36,"end":39},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C63604"},{"id":"T153","span":{"begin":36,"end":39},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C9697"},{"id":"T161","span":{"begin":36,"end":39},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C126526"},{"id":"T169","span":{"begin":36,"end":39},"obj":"http://purl.obolibrary.org/obo/PR_000004959"},{"id":"T177","span":{"begin":36,"end":39},"obj":"http://purl.obolibrary.org/obo/PR_000006430"},{"id":"T185","span":{"begin":40,"end":44},"obj":"http://purl.org/sig/ont/fma/fma74402"},{"id":"T189","span":{"begin":40,"end":44},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/67271001"},{"id":"T193","span":{"begin":40,"end":44},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C45520"},{"id":"T197","span":{"begin":40,"end":44},"obj":"http://purl.obolibrary.org/obo/SO_0000704"},{"id":"T201","span":{"begin":40,"end":44},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C16612"},{"id":"T205","span":{"begin":48,"end":72},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C113839"},{"id":"T211","span":{"begin":48,"end":55},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C3890"},{"id":"T216","span":{"begin":48,"end":55},"obj":"http://purl.bioontology.org/ontology/SNOMEDCT/389086002"},{"id":"T221","span":{"begin":48,"end":55},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C58188"},{"id":"T226","span":{"begin":48,"end":55},"obj":"http://purl.bioontology.org/ontology/NDFRT/N0000000426"},{"id":"T231","span":{"begin":48,"end":55},"obj":"http://purl.bioontology.org/ontology/OMIM/MTHU016005"},{"id":"T236","span":{"begin":48,"end":55},"obj":"http://purl.bioontology.org/ontology/MEDDRA/10021143"},{"id":"T241","span":{"begin":48,"end":55},"obj":"http://purl.bioontology.org/ontology/MESH/D000860"},{"id":"T246","span":{"begin":56,"end":65},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C61367"},{"id":"T248","span":{"begin":66,"end":72},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C25506"},{"id":"T249","span":{"begin":66,"end":72},"obj":"http://ncicb.nci.nih.gov/xml/owl/EVS/Thesaurus.owl#C84380"}],"namespaces":[{"prefix":"omim","uri":"http://purl.bioontology.org/ontology/OMIM/"},{"prefix":"pr","uri":"http://purl.obolibrary.org/obo/PR_"}],"attributes":[{"subj":"T8","pred":"source","obj":"Biotea"},{"subj":"T5","pred":"source","obj":"Biotea"},{"subj":"T6","pred":"source","obj":"Biotea"},{"subj":"T9","pred":"source","obj":"Biotea"},{"subj":"T11","pred":"source","obj":"Biotea"},{"subj":"T12","pred":"source","obj":"Biotea"},{"subj":"T14","pred":"source","obj":"Biotea"},{"subj":"T15","pred":"source","obj":"Biotea"},{"subj":"T17","pred":"source","obj":"Biotea"},{"subj":"T18","pred":"source","obj":"Biotea"},{"subj":"T20","pred":"source","obj":"Biotea"},{"subj":"T21","pred":"source","obj":"Biotea"},{"subj":"T23","pred":"source","obj":"Biotea"},{"subj":"T24","pred":"source","obj":"Biotea"},{"subj":"T26","pred":"source","obj":"Biotea"},{"subj":"T27","pred":"source","obj":"Biotea"},{"subj":"T29","pred":"source","obj":"Biotea"},{"subj":"T30","pred":"source","obj":"Biotea"},{"subj":"T32","pred":"source","obj":"Biotea"},{"subj":"T33","pred":"source","obj":"Biotea"},{"subj":"T35","pred":"source","obj":"Biotea"},{"subj":"T36","pred":"source","obj":"Biotea"},{"subj":"T38","pred":"source","obj":"Biotea"},{"subj":"T39","pred":"source","obj":"Biotea"},{"subj":"T42","pred":"source","obj":"Biotea"},{"subj":"T43","pred":"source","obj":"Biotea"},{"subj":"T44","pred":"source","obj":"Biotea"},{"subj":"T45","pred":"source","obj":"Biotea"},{"subj":"T46","pred":"source","obj":"Biotea"},{"subj":"T47","pred":"source","obj":"Biotea"},{"subj":"T48","pred":"source","obj":"Biotea"},{"subj":"T50","pred":"source","obj":"Biotea"},{"subj":"T51","pred":"source","obj":"Biotea"},{"subj":"T52","pred":"source","obj":"Biotea"},{"subj":"T53","pred":"source","obj":"Biotea"},{"subj":"T54","pred":"source","obj":"Biotea"},{"subj":"T55","pred":"source","obj":"Biotea"},{"subj":"T56","pred":"source","obj":"Biotea"},{"subj":"T58","pred":"source","obj":"Biotea"},{"subj":"T59","pred":"source","obj":"Biotea"},{"subj":"T60","pred":"source","obj":"Biotea"},{"subj":"T61","pred":"source","obj":"Biotea"},{"subj":"T62","pred":"source","obj":"Biotea"},{"subj":"T63","pred":"source","obj":"Biotea"},{"subj":"T64","pred":"source","obj":"Biotea"},{"subj":"T66","pred":"source","obj":"Biotea"},{"subj":"T67","pred":"source","obj":"Biotea"},{"subj":"T68","pred":"source","obj":"Biotea"},{"subj":"T69","pred":"source","obj":"Biotea"},{"subj":"T70","pred":"source","obj":"Biotea"},{"subj":"T71","pred":"source","obj":"Biotea"},{"subj":"T72","pred":"source","obj":"Biotea"},{"subj":"T74","pred":"source","obj":"Biotea"},{"subj":"T75","pred":"source","obj":"Biotea"},{"subj":"T76","pred":"source","obj":"Biotea"},{"subj":"T77","pred":"source","obj":"Biotea"},{"subj":"T78","pred":"source","obj":"Biotea"},{"subj":"T79","pred":"source","obj":"Biotea"},{"subj":"T80","pred":"source","obj":"Biotea"},{"subj":"T82","pred":"source","obj":"Biotea"},{"subj":"T83","pred":"source","obj":"Biotea"},{"subj":"T84","pred":"source","obj":"Biotea"},{"subj":"T85","pred":"source","obj":"Biotea"},{"subj":"T86","pred":"source","obj":"Biotea"},{"subj":"T87","pred":"source","obj":"Biotea"},{"subj":"T88","pred":"source","obj":"Biotea"},{"subj":"T90","pred":"source","obj":"Biotea"},{"subj":"T91","pred":"source","obj":"Biotea"},{"subj":"T92","pred":"source","obj":"Biotea"},{"subj":"T93","pred":"source","obj":"Biotea"},{"subj":"T94","pred":"source","obj":"Biotea"},{"subj":"T95","pred":"source","obj":"Biotea"},{"subj":"T96","pred":"source","obj":"Biotea"},{"subj":"T98","pred":"source","obj":"Biotea"},{"subj":"T99","pred":"source","obj":"Biotea"},{"subj":"T100","pred":"source","obj":"Biotea"},{"subj":"T101","pred":"source","obj":"Biotea"},{"subj":"T102","pred":"source","obj":"Biotea"},{"subj":"T103","pred":"source","obj":"Biotea"},{"subj":"T104","pred":"source","obj":"Biotea"},{"subj":"T106","pred":"source","obj":"Biotea"},{"subj":"T107","pred":"source","obj":"Biotea"},{"subj":"T108","pred":"source","obj":"Biotea"},{"subj":"T109","pred":"source","obj":"Biotea"},{"subj":"T110","pred":"source","obj":"Biotea"},{"subj":"T111","pred":"source","obj":"Biotea"},{"subj":"T112","pred":"source","obj":"Biotea"},{"subj":"T114","pred":"source","obj":"Biotea"},{"subj":"T115","pred":"source","obj":"Biotea"},{"subj":"T116","pred":"source","obj":"Biotea"},{"subj":"T117","pred":"source","obj":"Biotea"},{"subj":"T118","pred":"source","obj":"Biotea"},{"subj":"T119","pred":"source","obj":"Biotea"},{"subj":"T120","pred":"source","obj":"Biotea"},{"subj":"T122","pred":"source","obj":"Biotea"},{"subj":"T123","pred":"source","obj":"Biotea"},{"subj":"T124","pred":"source","obj":"Biotea"},{"subj":"T125","pred":"source","obj":"Biotea"},{"subj":"T126","pred":"source","obj":"Biotea"},{"subj":"T127","pred":"source","obj":"Biotea"},{"subj":"T128","pred":"source","obj":"Biotea"},{"subj":"T130","pred":"source","obj":"Biotea"},{"subj":"T131","pred":"source","obj":"Biotea"},{"subj":"T132","pred":"source","obj":"Biotea"},{"subj":"T133","pred":"source","obj":"Biotea"},{"subj":"T134","pred":"source","obj":"Biotea"},{"subj":"T135","pred":"source","obj":"Biotea"},{"subj":"T136","pred":"source","obj":"Biotea"},{"subj":"T138","pred":"source","obj":"Biotea"},{"subj":"T139","pred":"source","obj":"Biotea"},{"subj":"T140","pred":"source","obj":"Biotea"},{"subj":"T141","pred":"source","obj":"Biotea"},{"subj":"T142","pred":"source","obj":"Biotea"},{"subj":"T143","pred":"source","obj":"Biotea"},{"subj":"T144","pred":"source","obj":"Biotea"},{"subj":"T146","pred":"source","obj":"Biotea"},{"subj":"T147","pred":"source","obj":"Biotea"},{"subj":"T148","pred":"source","obj":"Biotea"},{"subj":"T149","pred":"source","obj":"Biotea"},{"subj":"T150","pred":"source","obj":"Biotea"},{"subj":"T151","pred":"source","obj":"Biotea"},{"subj":"T152","pred":"source","obj":"Biotea"},{"subj":"T154","pred":"source","obj":"Biotea"},{"subj":"T155","pred":"source","obj":"Biotea"},{"subj":"T156","pred":"source","obj":"Biotea"},{"subj":"T157","pred":"source","obj":"Biotea"},{"subj":"T158","pred":"source","obj":"Biotea"},{"subj":"T159","pred":"source","obj":"Biotea"},{"subj":"T160","pred":"source","obj":"Biotea"},{"subj":"T162","pred":"source","obj":"Biotea"},{"subj":"T163","pred":"source","obj":"Biotea"},{"subj":"T164","pred":"source","obj":"Biotea"},{"subj":"T165","pred":"source","obj":"Biotea"},{"subj":"T166","pred":"source","obj":"Biotea"},{"subj":"T167","pred":"source","obj":"Biotea"},{"subj":"T168","pred":"source","obj":"Biotea"},{"subj":"T170","pred":"source","obj":"Biotea"},{"subj":"T171","pred":"source","obj":"Biotea"},{"subj":"T172","pred":"source","obj":"Biotea"},{"subj":"T173","pred":"source","obj":"Biotea"},{"subj":"T174","pred":"source","obj":"Biotea"},{"subj":"T175","pred":"source","obj":"Biotea"},{"subj":"T176","pred":"source","obj":"Biotea"},{"subj":"T178","pred":"source","obj":"Biotea"},{"subj":"T179","pred":"source","obj":"Biotea"},{"subj":"T180","pred":"source","obj":"Biotea"},{"subj":"T181","pred":"source","obj":"Biotea"},{"subj":"T182","pred":"source","obj":"Biotea"},{"subj":"T183","pred":"source","obj":"Biotea"},{"subj":"T184","pred":"source","obj":"Biotea"},{"subj":"T186","pred":"source","obj":"Biotea"},{"subj":"T187","pred":"source","obj":"Biotea"},{"subj":"T188","pred":"source","obj":"Biotea"},{"subj":"T190","pred":"source","obj":"Biotea"},{"subj":"T191","pred":"source","obj":"Biotea"},{"subj":"T192","pred":"source","obj":"Biotea"},{"subj":"T194","pred":"source","obj":"Biotea"},{"subj":"T195","pred":"source","obj":"Biotea"},{"subj":"T196","pred":"source","obj":"Biotea"},{"subj":"T198","pred":"source","obj":"Biotea"},{"subj":"T199","pred":"source","obj":"Biotea"},{"subj":"T200","pred":"source","obj":"Biotea"},{"subj":"T202","pred":"source","obj":"Biotea"},{"subj":"T203","pred":"source","obj":"Biotea"},{"subj":"T204","pred":"source","obj":"Biotea"},{"subj":"T206","pred":"source","obj":"Biotea"},{"subj":"T207","pred":"source","obj":"Biotea"},{"subj":"T208","pred":"source","obj":"Biotea"},{"subj":"T209","pred":"source","obj":"Biotea"},{"subj":"T210","pred":"source","obj":"Biotea"},{"subj":"T212","pred":"source","obj":"Biotea"},{"subj":"T213","pred":"source","obj":"Biotea"},{"subj":"T214","pred":"source","obj":"Biotea"},{"subj":"T215","pred":"source","obj":"Biotea"},{"subj":"T217","pred":"source","obj":"Biotea"},{"subj":"T218","pred":"source","obj":"Biotea"},{"subj":"T219","pred":"source","obj":"Biotea"},{"subj":"T220","pred":"source","obj":"Biotea"},{"subj":"T222","pred":"source","obj":"Biotea"},{"subj":"T223","pred":"source","obj":"Biotea"},{"subj":"T224","pred":"source","obj":"Biotea"},{"subj":"T225","pred":"source","obj":"Biotea"},{"subj":"T227","pred":"source","obj":"Biotea"},{"subj":"T228","pred":"source","obj":"Biotea"},{"subj":"T229","pred":"source","obj":"Biotea"},{"subj":"T230","pred":"source","obj":"Biotea"},{"subj":"T232","pred":"source","obj":"Biotea"},{"subj":"T233","pred":"source","obj":"Biotea"},{"subj":"T234","pred":"source","obj":"Biotea"},{"subj":"T235","pred":"source","obj":"Biotea"},{"subj":"T237","pred":"source","obj":"Biotea"},{"subj":"T238","pred":"source","obj":"Biotea"},{"subj":"T239","pred":"source","obj":"Biotea"},{"subj":"T240","pred":"source","obj":"Biotea"},{"subj":"T242","pred":"source","obj":"Biotea"},{"subj":"T243","pred":"source","obj":"Biotea"},{"subj":"T244","pred":"source","obj":"Biotea"},{"subj":"T245","pred":"source","obj":"Biotea"},{"subj":"T247","pred":"source","obj":"Biotea"},{"subj":"T250","pred":"source","obj":"Biotea"},{"subj":"T251","pred":"source","obj":"Biotea"},{"subj":"T252","pred":"source","obj":"Biotea"},{"subj":"T253","pred":"source","obj":"Biotea"},{"subj":"T254","pred":"source","obj":"Biotea"},{"subj":"T255","pred":"source","obj":"Biotea"},{"subj":"T256","pred":"source","obj":"Biotea"},{"subj":"T257","pred":"source","obj":"Biotea"},{"subj":"T258","pred":"source","obj":"Biotea"},{"subj":"T259","pred":"source","obj":"Biotea"},{"subj":"T260","pred":"source","obj":"Biotea"},{"subj":"T261","pred":"source","obj":"Biotea"},{"subj":"T262","pred":"source","obj":"Biotea"},{"subj":"T263","pred":"source","obj":"Biotea"},{"subj":"T264","pred":"source","obj":"Biotea"},{"subj":"T265","pred":"source","obj":"Biotea"},{"subj":"T266","pred":"source","obj":"Biotea"},{"subj":"T267","pred":"source","obj":"Biotea"},{"subj":"T268","pred":"source","obj":"Biotea"},{"subj":"T269","pred":"source","obj":"Biotea"},{"subj":"T270","pred":"source","obj":"Biotea"},{"subj":"T271","pred":"source","obj":"Biotea"},{"subj":"T272","pred":"source","obj":"Biotea"},{"subj":"T273","pred":"source","obj":"Biotea"},{"subj":"T274","pred":"source","obj":"Biotea"},{"subj":"T275","pred":"source","obj":"Biotea"},{"subj":"T276","pred":"source","obj":"Biotea"},{"subj":"T277","pred":"source","obj":"Biotea"},{"subj":"T278","pred":"source","obj":"Biotea"},{"subj":"T279","pred":"source","obj":"Biotea"},{"subj":"T280","pred":"source","obj":"Biotea"},{"subj":"T281","pred":"source","obj":"Biotea"},{"subj":"T282","pred":"source","obj":"Biotea"},{"subj":"T283","pred":"source","obj":"Biotea"},{"subj":"T284","pred":"source","obj":"Biotea"},{"subj":"T285","pred":"source","obj":"Biotea"},{"subj":"T286","pred":"source","obj":"Biotea"},{"subj":"T287","pred":"source","obj":"Biotea"},{"subj":"T288","pred":"source","obj":"Biotea"},{"subj":"T289","pred":"source","obj":"Biotea"},{"subj":"T290","pred":"source","obj":"Biotea"},{"subj":"T291","pred":"source","obj":"Biotea"},{"subj":"T292","pred":"source","obj":"Biotea"},{"subj":"T293","pred":"source","obj":"Biotea"},{"subj":"T294","pred":"source","obj":"Biotea"},{"subj":"T295","pred":"source","obj":"Biotea"},{"subj":"T296","pred":"source","obj":"Biotea"},{"subj":"T297","pred":"source","obj":"Biotea"},{"subj":"T298","pred":"source","obj":"Biotea"},{"subj":"T299","pred":"source","obj":"Biotea"},{"subj":"T300","pred":"source","obj":"Biotea"},{"subj":"T301","pred":"source","obj":"Biotea"},{"subj":"T302","pred":"source","obj":"Biotea"},{"subj":"T303","pred":"source","obj":"Biotea"},{"subj":"T304","pred":"source","obj":"Biotea"},{"subj":"T305","pred":"source","obj":"Biotea"},{"subj":"T306","pred":"source","obj":"Biotea"},{"subj":"T307","pred":"source","obj":"Biotea"},{"subj":"T308","pred":"source","obj":"Biotea"},{"subj":"T309","pred":"source","obj":"Biotea"},{"subj":"T310","pred":"source","obj":"Biotea"},{"subj":"T311","pred":"source","obj":"Biotea"},{"subj":"T312","pred":"source","obj":"Biotea"},{"subj":"T313","pred":"source","obj":"Biotea"},{"subj":"T314","pred":"source","obj":"Biotea"},{"subj":"T315","pred":"source","obj":"Biotea"},{"subj":"T316","pred":"source","obj":"Biotea"},{"subj":"T317","pred":"source","obj":"Biotea"},{"subj":"T318","pred":"source","obj":"Biotea"},{"subj":"T319","pred":"source","obj":"Biotea"},{"subj":"T320","pred":"source","obj":"Biotea"},{"subj":"T321","pred":"source","obj":"Biotea"},{"subj":"T322","pred":"source","obj":"Biotea"},{"subj":"T323","pred":"source","obj":"Biotea"},{"subj":"T324","pred":"source","obj":"Biotea"},{"subj":"T325","pred":"source","obj":"Biotea"},{"subj":"T326","pred":"source","obj":"Biotea"},{"subj":"T327","pred":"source","obj":"Biotea"},{"subj":"T328","pred":"source","obj":"Biotea"},{"subj":"T329","pred":"source","obj":"Biotea"},{"subj":"T330","pred":"source","obj":"Biotea"},{"subj":"T331","pred":"source","obj":"Biotea"},{"subj":"T332","pred":"source","obj":"Biotea"},{"subj":"T333","pred":"source","obj":"Biotea"},{"subj":"T334","pred":"source","obj":"Biotea"},{"subj":"T335","pred":"source","obj":"Biotea"},{"subj":"T336","pred":"source","obj":"Biotea"},{"subj":"T337","pred":"source","obj":"Biotea"},{"subj":"T338","pred":"source","obj":"Biotea"},{"subj":"T339","pred":"source","obj":"Biotea"},{"subj":"T340","pred":"source","obj":"Biotea"},{"subj":"T341","pred":"source","obj":"Biotea"},{"subj":"T342","pred":"source","obj":"Biotea"},{"subj":"T343","pred":"source","obj":"Biotea"},{"subj":"T344","pred":"source","obj":"Biotea"},{"subj":"T345","pred":"source","obj":"Biotea"},{"subj":"T346","pred":"source","obj":"Biotea"},{"subj":"T347","pred":"source","obj":"Biotea"},{"subj":"T348","pred":"source","obj":"Biotea"},{"subj":"T349","pred":"source","obj":"Biotea"},{"subj":"T350","pred":"source","obj":"Biotea"},{"subj":"T351","pred":"source","obj":"Biotea"},{"subj":"T352","pred":"source","obj":"Biotea"},{"subj":"T353","pred":"source","obj":"Biotea"},{"subj":"T354","pred":"source","obj":"Biotea"},{"subj":"T355","pred":"source","obj":"Biotea"},{"subj":"T356","pred":"source","obj":"Biotea"},{"subj":"T357","pred":"source","obj":"Biotea"},{"subj":"T358","pred":"source","obj":"Biotea"},{"subj":"T359","pred":"source","obj":"Biotea"},{"subj":"T360","pred":"source","obj":"Biotea"},{"subj":"T361","pred":"source","obj":"Biotea"},{"subj":"T362","pred":"source","obj":"Biotea"},{"subj":"T363","pred":"source","obj":"Biotea"},{"subj":"T364","pred":"source","obj":"Biotea"},{"subj":"T365","pred":"source","obj":"Biotea"},{"subj":"T366","pred":"source","obj":"Biotea"},{"subj":"T367","pred":"source","obj":"Biotea"},{"subj":"T368","pred":"source","obj":"Biotea"},{"subj":"T369","pred":"source","obj":"Biotea"},{"subj":"T370","pred":"source","obj":"Biotea"},{"subj":"T371","pred":"source","obj":"Biotea"},{"subj":"T372","pred":"source","obj":"Biotea"},{"subj":"T373","pred":"source","obj":"Biotea"},{"subj":"T374","pred":"source","obj":"Biotea"},{"subj":"T375","pred":"source","obj":"Biotea"},{"subj":"T376","pred":"source","obj":"Biotea"},{"subj":"T377","pred":"source","obj":"Biotea"},{"subj":"T378","pred":"source","obj":"Biotea"},{"subj":"T379","pred":"source","obj":"Biotea"},{"subj":"T380","pred":"source","obj":"Biotea"},{"subj":"T381","pred":"source","obj":"Biotea"},{"subj":"T382","pred":"source","obj":"Biotea"},{"subj":"T383","pred":"source","obj":"Biotea"},{"subj":"T384","pred":"source","obj":"Biotea"},{"subj":"T385","pred":"source","obj":"Biotea"},{"subj":"T386","pred":"source","obj":"Biotea"},{"subj":"T387","pred":"source","obj":"Biotea"},{"subj":"T388","pred":"source","obj":"Biotea"},{"subj":"T389","pred":"source","obj":"Biotea"},{"subj":"T390","pred":"source","obj":"Biotea"},{"subj":"T391","pred":"source","obj":"Biotea"},{"subj":"T392","pred":"source","obj":"Biotea"},{"subj":"T393","pred":"source","obj":"Biotea"},{"subj":"T394","pred":"source","obj":"Biotea"},{"subj":"T395","pred":"source","obj":"Biotea"},{"subj":"T396","pred":"source","obj":"Biotea"},{"subj":"T397","pred":"source","obj":"Biotea"},{"subj":"T398","pred":"source","obj":"Biotea"},{"subj":"T399","pred":"source","obj":"Biotea"},{"subj":"T400","pred":"source","obj":"Biotea"},{"subj":"T401","pred":"source","obj":"Biotea"},{"subj":"T402","pred":"source","obj":"Biotea"},{"subj":"T403","pred":"source","obj":"Biotea"},{"subj":"T404","pred":"source","obj":"Biotea"},{"subj":"T405","pred":"source","obj":"Biotea"},{"subj":"T406","pred":"source","obj":"Biotea"},{"subj":"T407","pred":"source","obj":"Biotea"},{"subj":"T408","pred":"source","obj":"Biotea"},{"subj":"T409","pred":"source","obj":"Biotea"},{"subj":"T410","pred":"source","obj":"Biotea"},{"subj":"T411","pred":"source","obj":"Biotea"},{"subj":"T412","pred":"source","obj":"Biotea"},{"subj":"T413","pred":"source","obj":"Biotea"},{"subj":"T414","pred":"source","obj":"Biotea"},{"subj":"T415","pred":"source","obj":"Biotea"},{"subj":"T416","pred":"source","obj":"Biotea"},{"subj":"T417","pred":"source","obj":"Biotea"},{"subj":"T418","pred":"source","obj":"Biotea"},{"subj":"T419","pred":"source","obj":"Biotea"},{"subj":"T420","pred":"source","obj":"Biotea"},{"subj":"T421","pred":"source","obj":"Biotea"},{"subj":"T422","pred":"source","obj":"Biotea"},{"subj":"T423","pred":"source","obj":"Biotea"},{"subj":"T424","pred":"source","obj":"Biotea"},{"subj":"T425","pred":"source","obj":"Biotea"},{"subj":"T426","pred":"source","obj":"Biotea"},{"subj":"T427","pred":"source","obj":"Biotea"},{"subj":"T428","pred":"source","obj":"Biotea"},{"subj":"T429","pred":"source","obj":"Biotea"},{"subj":"T430","pred":"source","obj":"Biotea"},{"subj":"T431","pred":"source","obj":"Biotea"},{"subj":"T432","pred":"source","obj":"Biotea"},{"subj":"T433","pred":"source","obj":"Biotea"},{"subj":"T434","pred":"source","obj":"Biotea"},{"subj":"T435","pred":"source","obj":"Biotea"},{"subj":"T436","pred":"source","obj":"Biotea"},{"subj":"T437","pred":"source","obj":"Biotea"},{"subj":"T438","pred":"source","obj":"Biotea"},{"subj":"T439","pred":"source","obj":"Biotea"},{"subj":"T440","pred":"source","obj":"Biotea"},{"subj":"T441","pred":"source","obj":"Biotea"},{"subj":"T442","pred":"source","obj":"Biotea"},{"subj":"T443","pred":"source","obj":"Biotea"},{"subj":"T444","pred":"source","obj":"Biotea"},{"subj":"T445","pred":"source","obj":"Biotea"},{"subj":"T446","pred":"source","obj":"Biotea"},{"subj":"T447","pred":"source","obj":"Biotea"},{"subj":"T448","pred":"source","obj":"Biotea"},{"subj":"T449","pred":"source","obj":"Biotea"},{"subj":"T450","pred":"source","obj":"Biotea"},{"subj":"T451","pred":"source","obj":"Biotea"},{"subj":"T452","pred":"source","obj":"Biotea"},{"subj":"T453","pred":"source","obj":"Biotea"},{"subj":"T454","pred":"source","obj":"Biotea"},{"subj":"T455","pred":"source","obj":"Biotea"},{"subj":"T456","pred":"source","obj":"Biotea"},{"subj":"T457","pred":"source","obj":"Biotea"},{"subj":"T458","pred":"source","obj":"Biotea"},{"subj":"T459","pred":"source","obj":"Biotea"},{"subj":"T460","pred":"source","obj":"Biotea"},{"subj":"T461","pred":"source","obj":"Biotea"},{"subj":"T462","pred":"source","obj":"Biotea"},{"subj":"T463","pred":"source","obj":"Biotea"},{"subj":"T464","pred":"source","obj":"Biotea"},{"subj":"T465","pred":"source","obj":"Biotea"},{"subj":"T466","pred":"source","obj":"Biotea"},{"subj":"T467","pred":"source","obj":"Biotea"},{"subj":"T468","pred":"source","obj":"Biotea"},{"subj":"T469","pred":"source","obj":"Biotea"},{"subj":"T470","pred":"source","obj":"Biotea"},{"subj":"T471","pred":"source","obj":"Biotea"},{"subj":"T472","pred":"source","obj":"Biotea"},{"subj":"T473","pred":"source","obj":"Biotea"},{"subj":"T474","pred":"source","obj":"Biotea"},{"subj":"T475","pred":"source","obj":"Biotea"},{"subj":"T476","pred":"source","obj":"Biotea"},{"subj":"T477","pred":"source","obj":"Biotea"},{"subj":"T478","pred":"source","obj":"Biotea"},{"subj":"T479","pred":"source","obj":"Biotea"},{"subj":"T480","pred":"source","obj":"Biotea"},{"subj":"T481","pred":"source","obj":"Biotea"},{"subj":"T482","pred":"source","obj":"Biotea"},{"subj":"T483","pred":"source","obj":"Biotea"},{"subj":"T484","pred":"source","obj":"Biotea"},{"subj":"T485","pred":"source","obj":"Biotea"},{"subj":"T486","pred":"source","obj":"Biotea"},{"subj":"T487","pred":"source","obj":"Biotea"},{"subj":"T488","pred":"source","obj":"Biotea"},{"subj":"T489","pred":"source","obj":"Biotea"},{"subj":"T490","pred":"source","obj":"Biotea"},{"subj":"T491","pred":"source","obj":"Biotea"},{"subj":"T492","pred":"source","obj":"Biotea"},{"subj":"T493","pred":"source","obj":"Biotea"},{"subj":"T494","pred":"source","obj":"Biotea"},{"subj":"T495","pred":"source","obj":"Biotea"},{"subj":"T496","pred":"source","obj":"Biotea"},{"subj":"T497","pred":"source","obj":"Biotea"},{"subj":"T498","pred":"source","obj":"Biotea"},{"subj":"T499","pred":"source","obj":"Biotea"},{"subj":"T500","pred":"source","obj":"Biotea"},{"subj":"T501","pred":"source","obj":"Biotea"},{"subj":"T502","pred":"source","obj":"Biotea"},{"subj":"T503","pred":"source","obj":"Biotea"},{"subj":"T504","pred":"source","obj":"Biotea"},{"subj":"T505","pred":"source","obj":"Biotea"},{"subj":"T506","pred":"source","obj":"Biotea"},{"subj":"T507","pred":"source","obj":"Biotea"},{"subj":"T508","pred":"source","obj":"Biotea"},{"subj":"T509","pred":"source","obj":"Biotea"},{"subj":"T510","pred":"source","obj":"Biotea"},{"subj":"T511","pred":"source","obj":"Biotea"},{"subj":"T512","pred":"source","obj":"Biotea"},{"subj":"T513","pred":"source","obj":"Biotea"},{"subj":"T514","pred":"source","obj":"Biotea"},{"subj":"T515","pred":"source","obj":"Biotea"},{"subj":"T516","pred":"source","obj":"Biotea"},{"subj":"T517","pred":"source","obj":"Biotea"},{"subj":"T518","pred":"source","obj":"Biotea"},{"subj":"T519","pred":"source","obj":"Biotea"},{"subj":"T520","pred":"source","obj":"Biotea"},{"subj":"T521","pred":"source","obj":"Biotea"},{"subj":"T522","pred":"source","obj":"Biotea"},{"subj":"T523","pred":"source","obj":"Biotea"},{"subj":"T524","pred":"source","obj":"Biotea"},{"subj":"T525","pred":"source","obj":"Biotea"},{"subj":"T526","pred":"source","obj":"Biotea"},{"subj":"T527","pred":"source","obj":"Biotea"},{"subj":"T528","pred":"source","obj":"Biotea"},{"subj":"T529","pred":"source","obj":"Biotea"},{"subj":"T530","pred":"source","obj":"Biotea"},{"subj":"T531","pred":"source","obj":"Biotea"},{"subj":"T532","pred":"source","obj":"Biotea"},{"subj":"T533","pred":"source","obj":"Biotea"},{"subj":"T534","pred":"source","obj":"Biotea"},{"subj":"T535","pred":"source","obj":"Biotea"},{"subj":"T536","pred":"source","obj":"Biotea"},{"subj":"T537","pred":"source","obj":"Biotea"},{"subj":"T538","pred":"source","obj":"Biotea"},{"subj":"T539","pred":"source","obj":"Biotea"},{"subj":"T540","pred":"source","obj":"Biotea"},{"subj":"T541","pred":"source","obj":"Biotea"},{"subj":"T542","pred":"source","obj":"Biotea"},{"subj":"T543","pred":"source","obj":"Biotea"},{"subj":"T544","pred":"source","obj":"Biotea"},{"subj":"T1","pred":"source","obj":"Biotea"},{"subj":"T2","pred":"source","obj":"Biotea"},{"subj":"T3","pred":"source","obj":"Biotea"},{"subj":"T4","pred":"source","obj":"Biotea"},{"subj":"T7","pred":"source","obj":"Biotea"},{"subj":"T10","pred":"source","obj":"Biotea"},{"subj":"T13","pred":"source","obj":"Biotea"},{"subj":"T16","pred":"source","obj":"Biotea"},{"subj":"T19","pred":"source","obj":"Biotea"},{"subj":"T22","pred":"source","obj":"Biotea"},{"subj":"T25","pred":"source","obj":"Biotea"},{"subj":"T28","pred":"source","obj":"Biotea"},{"subj":"T31","pred":"source","obj":"Biotea"},{"subj":"T34","pred":"source","obj":"Biotea"},{"subj":"T37","pred":"source","obj":"Biotea"},{"subj":"T40","pred":"source","obj":"Biotea"},{"subj":"T41","pred":"source","obj":"Biotea"},{"subj":"T49","pred":"source","obj":"Biotea"},{"subj":"T57","pred":"source","obj":"Biotea"},{"subj":"T65","pred":"source","obj":"Biotea"},{"subj":"T73","pred":"source","obj":"Biotea"},{"subj":"T81","pred":"source","obj":"Biotea"},{"subj":"T89","pred":"source","obj":"Biotea"},{"subj":"T97","pred":"source","obj":"Biotea"},{"subj":"T105","pred":"source","obj":"Biotea"},{"subj":"T113","pred":"source","obj":"Biotea"},{"subj":"T121","pred":"source","obj":"Biotea"},{"subj":"T129","pred":"source","obj":"Biotea"},{"subj":"T137","pred":"source","obj":"Biotea"},{"subj":"T145","pred":"source","obj":"Biotea"},{"subj":"T153","pred":"source","obj":"Biotea"},{"subj":"T161","pred":"source","obj":"Biotea"},{"subj":"T169","pred":"source","obj":"Biotea"},{"subj":"T177","pred":"source","obj":"Biotea"},{"subj":"T185","pred":"source","obj":"Biotea"},{"subj":"T189","pred":"source","obj":"Biotea"},{"subj":"T193","pred":"source","obj":"Biotea"},{"subj":"T197","pred":"source","obj":"Biotea"},{"subj":"T201","pred":"source","obj":"Biotea"},{"subj":"T205","pred":"source","obj":"Biotea"},{"subj":"T211","pred":"source","obj":"Biotea"},{"subj":"T216","pred":"source","obj":"Biotea"},{"subj":"T221","pred":"source","obj":"Biotea"},{"subj":"T226","pred":"source","obj":"Biotea"},{"subj":"T231","pred":"source","obj":"Biotea"},{"subj":"T236","pred":"source","obj":"Biotea"},{"subj":"T241","pred":"source","obj":"Biotea"},{"subj":"T246","pred":"source","obj":"Biotea"},{"subj":"T248","pred":"source","obj":"Biotea"},{"subj":"T249","pred":"source","obj":"Biotea"}]},{"project":"2_test","denotations":[{"id":"16155188-9528826-77089314","span":{"begin":1710,"end":1711},"obj":"9528826"},{"id":"16155188-8538748-77089314","span":{"begin":1710,"end":1711},"obj":"8538748"},{"id":"16155188-9566903-77089314","span":{"begin":1710,"end":1711},"obj":"9566903"},{"id":"16155188-12482987-77089314","span":{"begin":1710,"end":1711},"obj":"12482987"},{"id":"16155188-9697772-77089314","span":{"begin":1710,"end":1711},"obj":"9697772"},{"id":"16155188-11112789-77089314","span":{"begin":1710,"end":1711},"obj":"11112789"},{"id":"16155188-2721599-77089314","span":{"begin":1710,"end":1711},"obj":"2721599"},{"id":"16155188-11158306-77089314","span":{"begin":1710,"end":1711},"obj":"11158306"},{"id":"16155188-10749844-77089315","span":{"begin":2309,"end":2310},"obj":"10749844"},{"id":"16155188-8753788-77089316","span":{"begin":2503,"end":2505},"obj":"8753788"},{"id":"16155188-9000051-77089317","span":{"begin":2644,"end":2646},"obj":"9000051"},{"id":"16155188-9113979-77089317","span":{"begin":2644,"end":2646},"obj":"9113979"},{"id":"16155188-9365523-77089317","span":{"begin":2644,"end":2646},"obj":"9365523"},{"id":"16155188-9528826-77089318","span":{"begin":2878,"end":2879},"obj":"9528826"},{"id":"16155188-8538748-77089318","span":{"begin":2878,"end":2879},"obj":"8538748"},{"id":"16155188-9566903-77089318","span":{"begin":2878,"end":2879},"obj":"9566903"},{"id":"16155188-12482987-77089319","span":{"begin":3173,"end":3174},"obj":"12482987"},{"id":"16155188-9697772-77089319","span":{"begin":3173,"end":3174},"obj":"9697772"},{"id":"16155188-11112789-77089319","span":{"begin":3173,"end":3174},"obj":"11112789"},{"id":"16155188-2721599-77089319","span":{"begin":3173,"end":3174},"obj":"2721599"},{"id":"16155188-11158306-77089319","span":{"begin":3173,"end":3174},"obj":"11158306"},{"id":"16155188-9566903-77089320","span":{"begin":3428,"end":3429},"obj":"9566903"},{"id":"16155188-8065358-77089321","span":{"begin":3430,"end":3432},"obj":"8065358"},{"id":"16155188-11158306-77089322","span":{"begin":3645,"end":3646},"obj":"11158306"},{"id":"16155188-9528826-77089323","span":{"begin":3984,"end":3985},"obj":"9528826"},{"id":"16155188-19472-77089324","span":{"begin":4563,"end":4565},"obj":"19472"},{"id":"16155188-8619816-77089325","span":{"begin":4566,"end":4568},"obj":"8619816"},{"id":"16155188-6105839-77089326","span":{"begin":5058,"end":5060},"obj":"6105839"},{"id":"16155188-10659854-77089327","span":{"begin":5513,"end":5515},"obj":"10659854"},{"id":"16155188-12746293-77089328","span":{"begin":5516,"end":5518},"obj":"12746293"},{"id":"16155188-2721599-77089329","span":{"begin":5679,"end":5680},"obj":"2721599"},{"id":"16155188-3972010-77089330","span":{"begin":5681,"end":5683},"obj":"3972010"},{"id":"16155188-4085500-77089331","span":{"begin":5684,"end":5686},"obj":"4085500"},{"id":"16155188-2721599-77089332","span":{"begin":5811,"end":5812},"obj":"2721599"},{"id":"16155188-11739437-77089333","span":{"begin":6658,"end":6660},"obj":"11739437"},{"id":"16155188-12072406-77089334","span":{"begin":6661,"end":6663},"obj":"12072406"},{"id":"16155188-12933667-77089335","span":{"begin":8300,"end":8302},"obj":"12933667"},{"id":"16155188-12933667-77089336","span":{"begin":10971,"end":10973},"obj":"12933667"},{"id":"16155188-8538748-77089337","span":{"begin":15999,"end":16000},"obj":"8538748"},{"id":"16155188-7539918-77089338","span":{"begin":19310,"end":19312},"obj":"7539918"},{"id":"16155188-8756616-77089339","span":{"begin":19972,"end":19974},"obj":"8756616"},{"id":"16155188-2721599-77089340","span":{"begin":23247,"end":23248},"obj":"2721599"},{"id":"16155188-19472-77089341","span":{"begin":23547,"end":23549},"obj":"19472"},{"id":"16155188-8619816-77089342","span":{"begin":23550,"end":23552},"obj":"8619816"},{"id":"16155188-6736869-77089343","span":{"begin":24487,"end":24489},"obj":"6736869"},{"id":"16155188-11006282-77089344","span":{"begin":24889,"end":24891},"obj":"11006282"},{"id":"16155188-7947090-77089345","span":{"begin":24892,"end":24894},"obj":"7947090"},{"id":"16155188-19472-77089346","span":{"begin":24967,"end":24969},"obj":"19472"},{"id":"16155188-8619816-77089347","span":{"begin":24970,"end":24972},"obj":"8619816"},{"id":"16155188-9528826-77089348","span":{"begin":26096,"end":26097},"obj":"9528826"},{"id":"16155188-7892203-77089349","span":{"begin":26419,"end":26421},"obj":"7892203"},{"id":"16155188-14638687-77089350","span":{"begin":26422,"end":26424},"obj":"14638687"},{"id":"16155188-7539918-77089351","span":{"begin":26733,"end":26735},"obj":"7539918"},{"id":"16155188-7592839-77089352","span":{"begin":26736,"end":26738},"obj":"7592839"},{"id":"16155188-8662957-77089353","span":{"begin":26739,"end":26741},"obj":"8662957"},{"id":"16155188-12482987-77089354","span":{"begin":27864,"end":27865},"obj":"12482987"},{"id":"16155188-9811896-77089355","span":{"begin":28080,"end":28082},"obj":"9811896"},{"id":"16155188-15071503-77089356","span":{"begin":28224,"end":28226},"obj":"15071503"},{"id":"16155188-14559996-77089357","span":{"begin":28701,"end":28703},"obj":"14559996"}],"attributes":[{"subj":"16155188-9528826-77089314","pred":"source","obj":"2_test"},{"subj":"16155188-8538748-77089314","pred":"source","obj":"2_test"},{"subj":"16155188-9566903-77089314","pred":"source","obj":"2_test"},{"subj":"16155188-12482987-77089314","pred":"source","obj":"2_test"},{"subj":"16155188-9697772-77089314","pred":"source","obj":"2_test"},{"subj":"16155188-11112789-77089314","pred":"source","obj":"2_test"},{"subj":"16155188-2721599-77089314","pred":"source","obj":"2_test"},{"subj":"16155188-11158306-77089314","pred":"source","obj":"2_test"},{"subj":"16155188-10749844-77089315","pred":"source","obj":"2_test"},{"subj":"16155188-8753788-77089316","pred":"source","obj":"2_test"},{"subj":"16155188-9000051-77089317","pred":"source","obj":"2_test"},{"subj":"16155188-9113979-77089317","pred":"source","obj":"2_test"},{"subj":"16155188-9365523-77089317","pred":"source","obj":"2_test"},{"subj":"16155188-9528826-77089318","pred":"source","obj":"2_test"},{"subj":"16155188-8538748-77089318","pred":"source","obj":"2_test"},{"subj":"16155188-9566903-77089318","pred":"source","obj":"2_test"},{"subj":"16155188-12482987-77089319","pred":"source","obj":"2_test"},{"subj":"16155188-9697772-77089319","pred":"source","obj":"2_test"},{"subj":"16155188-11112789-77089319","pred":"source","obj":"2_test"},{"subj":"16155188-2721599-77089319","pred":"source","obj":"2_test"},{"subj":"16155188-11158306-77089319","pred":"source","obj":"2_test"},{"subj":"16155188-9566903-77089320","pred":"source","obj":"2_test"},{"subj":"16155188-8065358-77089321","pred":"source","obj":"2_test"},{"subj":"16155188-11158306-77089322","pred":"source","obj":"2_test"},{"subj":"16155188-9528826-77089323","pred":"source","obj":"2_test"},{"subj":"16155188-19472-77089324","pred":"source","obj":"2_test"},{"subj":"16155188-8619816-77089325","pred":"source","obj":"2_test"},{"subj":"16155188-6105839-77089326","pred":"source","obj":"2_test"},{"subj":"16155188-10659854-77089327","pred":"source","obj":"2_test"},{"subj":"16155188-12746293-77089328","pred":"source","obj":"2_test"},{"subj":"16155188-2721599-77089329","pred":"source","obj":"2_test"},{"subj":"16155188-3972010-77089330","pred":"source","obj":"2_test"},{"subj":"16155188-4085500-77089331","pred":"source","obj":"2_test"},{"subj":"16155188-2721599-77089332","pred":"source","obj":"2_test"},{"subj":"16155188-11739437-77089333","pred":"source","obj":"2_test"},{"subj":"16155188-12072406-77089334","pred":"source","obj":"2_test"},{"subj":"16155188-12933667-77089335","pred":"source","obj":"2_test"},{"subj":"16155188-12933667-77089336","pred":"source","obj":"2_test"},{"subj":"16155188-8538748-77089337","pred":"source","obj":"2_test"},{"subj":"16155188-7539918-77089338","pred":"source","obj":"2_test"},{"subj":"16155188-8756616-77089339","pred":"source","obj":"2_test"},{"subj":"16155188-2721599-77089340","pred":"source","obj":"2_test"},{"subj":"16155188-19472-77089341","pred":"source","obj":"2_test"},{"subj":"16155188-8619816-77089342","pred":"source","obj":"2_test"},{"subj":"16155188-6736869-77089343","pred":"source","obj":"2_test"},{"subj":"16155188-11006282-77089344","pred":"source","obj":"2_test"},{"subj":"16155188-7947090-77089345","pred":"source","obj":"2_test"},{"subj":"16155188-19472-77089346","pred":"source","obj":"2_test"},{"subj":"16155188-8619816-77089347","pred":"source","obj":"2_test"},{"subj":"16155188-9528826-77089348","pred":"source","obj":"2_test"},{"subj":"16155188-7892203-77089349","pred":"source","obj":"2_test"},{"subj":"16155188-14638687-77089350","pred":"source","obj":"2_test"},{"subj":"16155188-7539918-77089351","pred":"source","obj":"2_test"},{"subj":"16155188-7592839-77089352","pred":"source","obj":"2_test"},{"subj":"16155188-8662957-77089353","pred":"source","obj":"2_test"},{"subj":"16155188-12482987-77089354","pred":"source","obj":"2_test"},{"subj":"16155188-9811896-77089355","pred":"source","obj":"2_test"},{"subj":"16155188-15071503-77089356","pred":"source","obj":"2_test"},{"subj":"16155188-14559996-77089357","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"Biotea","color":"#93c7ec","default":true},{"id":"2_test","color":"#e1ec93"}]}]}}