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PMC4067800_CCD-5-272-g001.png
(a and b) Pretreatment photograph, (c) pretreatment orthopantomograph
An 18-year-old female patient was referred with the unesthetic appearance of her missing maxillary anterior teeth. On clinical examination revealed that an Angle Class I molar relationship, and the permanent left canine was not seen in the arch [Figure 1a and b] Palatal bulge was identified in the maxillary left palata...
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PMC4067800_CCD-5-272-g002.png
(a) Surgical exposure with open window technique, (b) lingual button bonded over exposed impacted left canine, (c) biomechanics of K-9 spring dotted horizontal arm indicates activation of K-9 spring, arrow indicates distal direction of force, (K-9 spring exerts eruptive force (70 g) and distal force on impacted canine)...
(a and b) Pretreatment photograph, (c) pretreatment orthopantomograph
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PMC4067800_CCD-5-272-g003.png
(a and b) Posttreatment intraoral photograph, (c) posttreatment orthopantomograph (OPG) (Treatment duration = 15 months), (d) superimposition of palatally impacted canine on OPG (path travelled by canine = 19 mm)
Overall, active treatment lasted for 15 months. There was a dramatic improvement in patient's smile. Canine guidance had been established bilaterally during lateral excursive movements. Posttreatment panoramic tracing on comparison with the pretreatment showed that the roots were well-angulated and aligned parallel, an...
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PMC3103432_1471-2091-12-18-1.png
Expression of human L1 reverse transcriptase in E. coli. (A) Domain structure of human L1 ORF2 protein. The conserved domains are shown as shaded rectangles. L1 RT domain (Aa 238-1061) was cloned into pMal-c2X downstream of MBP gene in frame. (B) Human L1 RT domain was expressed in E. coli as a fusion protein (MBP-RT) ...
Human L1 ORF2 encodes 1275 amino acids and contains three functional domains. Among them, the structure of EN domain (amino acids 1-239) has been determined [17,35]. The RT domain spans ~1/3 (amino acids ~380-773) of the ORF2 sequence and the cysteine-rich domain starts at amino acid ~1130 (Figure 1a). We cloned the RT...
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PMC3103432_1471-2091-12-18-2.png
Effect of RT inhibitors on the activities of HIV-1, L1 and Ty1 RTs. The reverse transcriptase activities of HIV-1 RT (blue diamond), L1 RT (red square) and Ty1 RT (green triangle) were measured as described in the materials and methods. The RT activity of control assay without inhibitors was considered as 1.0. The acti...
We tested the effect of four NRTIs and three NNRTIs on HIV-1, L1 and Ty1 reverse transcriptase activities. As shown in Figure 2A, B, C and 2D, all four triphosphate NRTIs markedly inhibited the activities of HIV-1 and L1 RTs at nM concentrations. Conversely, NRTIs inhibited Ty1 RT activity at the μM level, if at all. W...
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PMC3103432_1471-2091-12-18-3.png
Kinetic analysis of inhibition of L1 RT by NRTIs. The L1 RT activity was measured as described in materials and methods. (A) Double reciprocal plot of the velocity of the L1 RT activity as a function of [32P]-dTTP substrate concentration. Increasing concentrations of substrate in the absence (diamond) or presence of 2 ...
Having determined that all NRTIs inhibited L1 RT activity, we next studied the kinetics of inhibition of L1 RT by these NRTIs. Poly (rA)-oligo (dT)12-18 and [32P]-dTTP were used as template/primers and substrate to assay thymine analogs (AZTTP, d4TTP). Poly (rI)-oligo (dC)12-18 and [32P]-dCTP were used to assay cytidin...
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PMC3103432_1471-2091-12-18-4.png
Effect of RT inhibitors on ORFeus-Hs retrotransposition efficiency. A tissue culture cell-based L1 retrotransposition assay was done as described in materials and methods. Example plates from retrotransposition assay indicating different effects of RT inhibitors on L1 retrotransposition. See Table 2 for details.
To further evaluate the effect of RT inhibitors on L1 in vivo, we tested L1 retrotransposition in the presence of these chemicals using an established tissue culture retrotransposition assay. All transposition assays were performed using ORFeus-Hs that encodes wild type ORF1 and ORF2 proteins but transposes at a 2~3 fo...
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PMC3974040_1471-2334-14-98-1.png
A chest radiograph of the index case is shown in Panel A and B on day 6 after the onset of the illness. A computed tomography scan of the chest of the index case is shown in Panel C and D after the onset of the illness.
The index case, 36 year old man, lived with his wife, two daughters and his son. He presented to a clinic with fever (37.8°C) and cough on April 16. He felt well after taking compound paracetamol tablets (II), Ibuprofen Tablets and Radix Isatidis on April 17. On April 18, he continued fever and developed pneumonia and ...
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PMC3974040_1471-2334-14-98-2.png
The surround environment of the confirmed H7N9 case patients.
The index case lived in rural–urban fringe zone in Zaozhuang City. There were several living chicken in the cage and vegetable gardens fertilized with fences in the living community away 10 meters from their apartment. And there were two living poultry slaughter sites in the Mazhuang Farm Market located 500 and 1000 me...
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PMC3974040_1471-2334-14-98-3.png
Timeline of patient exposures and dates of illness onset in the family cluster of cases of H7N9 Virus infection. Note: ICU denotes intensive care unit, and rRT-PCR real-time reverse-transcriptase–polymerase-chain-reaction assay.
The index case lived in rural–urban fringe zone in Zaozhuang City. There were several living chicken in the cage and vegetable gardens fertilized with fences in the living community away 10 meters from their apartment. And there were two living poultry slaughter sites in the Mazhuang Farm Market located 500 and 1000 me...
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PMC2800191_pone.0008682.g001.png
Cytotoxicity of EGCG on Plasmodium sporozoites.The percentage of living parasites after application of different EGCG concentrations from 12.5 µg/ml to 2000 µg/ml (27 µM - 4400 µM) was determined over 18 h. A) Snap shots of parasites after treatment with 200 µg/ml EGCG at the start of the experiment and after 6 and 12 ...
We first performed a cytotoxicity assay over 18 h with EGCG concentrations ranging from 12.5 µg/ml to 2000 µg/ml (27 µM to 4400 µM) by imaging Plasmodium sporozoites expressing the green fluorescent protein (GFP). Living parasites were distinguished by their cytoplasmic green fluorescence from dead parasites that lost ...
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PMC2800191_pone.0008682.g002.png
Inhibition of gliding motility by EGCG.The percentage of gliding parasites after treatment with EGCG in a range from 3.125 µg/ml to 500 µg/ml (6.75 µM to 1090 µM) was determined. A) Inverted maximum projections of time-lapse movies from untreated sporozoites and sporozoites treated with 100 µg/ml or 500 µg/ml. As sporo...
To test for a possible effect of EGCG on sporozoite gliding motility, sporozoites exposed to EGCG concentrations ranging from 3.125 to 500 µg/ml (6.75 to 1090 µM) were imaged 40 min after incubation with the drugs. Maximum fluorescent intensity projections of gliding parasites showed that gliding was inhibited to aroun...
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PMC2800191_pone.0008682.g003.png
Permeabilisation efficiency of digitonin.A) Snap shots of non-treated sporozoites and sporozoites treated with 250 and 500 µg/ml digitonin after 40 min of incubation. The upper panels show the green, the lower panels the red fluorescent signal. Scale bar: 25 µm. B) The percentage of living parasites (normalised to the ...
While the effect of EGCG on parasite gliding could be due to the unspecific binding and blocking of proteins at the parasite surface, the effect on viability could additionally be mediated by interactions of EGCG with intracellular targets. Since EGCG does not effectively cross the plasma membrane of the sporozoites, w...
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PMC2800191_pone.0008682.g004.png
Cytotoxicity of EGCG combined with digitonin.The percentage of living parasites (normalised to the control set to 100%) after exposure to a low A) or high B) concentration of EGCG, combined with digitonin in a range from 40 to 70 µg/ml (40 = grey line with filled circle; 50 = grey line with cross; 60 = light grey line ...
To determine possible additive or synergistic effects we next performed cytotoxicity assays over 18 h after application of EGCG concentrations from 12.5 µg/ml to 1000 µg/ml together with either 40, 50, 60 or 70 µg/ml digitonin. The data was normalised to the measured death curves of 40, 50, 60 and 70 µg/ml digitonin al...
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PMC2800191_pone.0008682.g005.png
Synergistic cytotoxicity of EGCG and digitonin.The percentage of living parasites over (normalised to the control set to 100%) the concentrations of EGCG (dashed grey lines, already shown in Figure 1) and EGCG with 60 µg/ml (115 µM) digitonin was plotted at the beginning of the experiment (straight line on top), after ...
To determine possible additive or synergistic effects we next performed cytotoxicity assays over 18 h after application of EGCG concentrations from 12.5 µg/ml to 1000 µg/ml together with either 40, 50, 60 or 70 µg/ml digitonin. The data was normalised to the measured death curves of 40, 50, 60 and 70 µg/ml digitonin al...
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PMC2800191_pone.0008682.g006.png
Inhibition of gliding motility by EGCG and digitonin.Concentration dependent inhibition of gliding sporozoites (normalised to the control set to 100%) treated with different EGCG concentrations and permeabilised with 50 (open circles), 60 (filled squares), 65 (crosses) and 70 (filled rhombi) µg/ml digitonin. IC50 value...
We next tested for a possible synergistic effect of EGCG together with digitonin on the inhibition of sporozoite motility after 40 minutes. EGCG was applied over the entire concentration range together with 50, 60 and 70 µg/ml digitonin (Figure 6). The application of 50 µg/ml digitonin did not result in an increased ef...
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PMC5041559_12885_2016_2792_Fig1_HTML.png
Promoter activities in lung cancer. (a) An MDS plot. Similarities (distances) between individual carcinomas in the space of promoter activities (CAGE profiles) are visualized in two dimensions by the multi-dimensional scaling implemented in the edgeR [20], where individual dots represent individual carcinomas and simil...
We obtained quantitative promoter activity profiles from 97 lung cancer tissues, consisting of 75 AD and 22 SCC, using a CAGE protocol [7] with a next generation sequencer (HiSeq2500). The two types of carcinoma are known to show different expression patterns [22], which were confirmed in our CAGE data (Fig. 1a). We al...
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PMC5041559_12885_2016_2792_Fig2_HTML.png
Promoter activity levels of known markers and novel candidates. (a) The promoter activities of known markers for AD and the novel candidate are shown in boxplots based on the carcinoma subtypes. (b) Equivalent boxplots for known markers of SCC and the candidate
As shown in Fig. 2a, SPATS2 was active in SCC, particularly PDSCC, and less active in AD overall. Notably, it was more active in PDSCC than differentiated SCC (DSCC), which is unique for this molecule. In contrast, ST6GALNAC1 was almost absent only in PDSCC (<1 cpm; Fig. 2b). TTF-1, one of the known AD markers, was ...
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PMC5041559_12885_2016_2792_Fig3_HTML.png
IHC for the novel marker candidates. A case of pure lepidic AD (a-d). H.E. staining (a) and IHC for TTF-1 (b), SPATS2 (c) and ST6GALNAC1 (d). The tumor cells are diffusely positive for ST6GALNAC1, but negative for TTF1 and SPATS2. A case of non-lepidic AD (e-h). H.E. staining (e) and IHC for TTF-1 (f), SPATS2 (g) and S...
We next examined the candidate biomarkers at the protein level. We performed an IHC analysis on paraffin-embedded tumors obtained from the same patients analyzed by CAGE above, and found clear contrasts between the staining patterns of SPATS2 and ST6GALNAC1 between AD and SCC, even in the PD form of each tumor type (Fi...
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PMC5041559_12885_2016_2792_Fig4_HTML.png
The results of IHC with the novel and known markers. (a) The presence of the known markers and the candidate markers was examined by IHC of carcinoma tissues of non-lepidic AD and PDSCC obtained from the same patients evaluated in the CAGE analysis. The staining patterns are scored (IHC score 0, 1, and 2) as described ...
We then examined the performance of the new markers in comparison with the existing markers by IHC. Paraffin-embedded tumors obtained from the same patients used in the CAGE analysis were immunostained for the six known markers, as well as two novel marker candidates. The heatmap showing the staining scores (Fig. 4a) i...
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PMC4129580_AJNS-9-68-g001.png
Site of lesion
A total of 27 patients were operated for spinal dysraphism during one-year period. There were 17 males and 11 females. Median age was 120 days (age range, 1 day to 6 years). Fifteen mothers did not seek regular antenatal checkup and similar number did not receive folic acid supplementation during pregnancy. Fourteen pa...
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PMC4129580_AJNS-9-68-g002.png
Associated lesions
A total of 27 patients were operated for spinal dysraphism during one-year period. There were 17 males and 11 females. Median age was 120 days (age range, 1 day to 6 years). Fifteen mothers did not seek regular antenatal checkup and similar number did not receive folic acid supplementation during pregnancy. Fourteen pa...
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PMC4129580_AJNS-9-68-g003.png
Clinical photograph showing ruptured meningocele sac that was repaired
A total of 27 patients were operated for spinal dysraphism during one-year period. There were 17 males and 11 females. Median age was 120 days (age range, 1 day to 6 years). Fifteen mothers did not seek regular antenatal checkup and similar number did not receive folic acid supplementation during pregnancy. Fourteen pa...
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PMC5290280_ncomms14286-f1.png
In vitro orthogonal reactivity of the xUB-xUba6 and xUB-xUba1 pairs.(a) xUB and wt UB activation by the xE1 and wt E1 enzymes in the ATP-PPi exchange assay. Data are shown as means±s.e.m. (n=3). (b) Formation of UB∼E1 and UB∼E2 thioester conjugates with xUB and xUba1. UBE2D2/UbcH5b was used as the E2. Cross-reactivity ...
We previously used phage display to engineer an xUB-xUba1 pair with Uba1 from Saccharomyces cerevisiae to enable the activation of xUB by xUba1 (ref. 18). Mutations R42E and R72E were incorporated into xUB to block its recognition by wt Uba1. Subsequently, mutations Q576R, S589R and D591R were introduced into the adeny...
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PMC5290280_ncomms14286-f2.png
Profiling cellular substrates of Uba6- and Uba1-dependent ubiquitination.(a) Flow chart of procedures to identify xUba6- and xUba1-dependent ubiquitination substrates by tandem affinity purification and proteomic procedures. (b) Specific reactions of the xUB-xUba1 pair and the xUB-xUba6 pair in HEK293 cells with lentiv...
The orthogonal xUB-xUba1 and xUB-xUba6 pairs provided a platform to track xUB transfer and identify cellular ubiquitination targets in xUba6- or xUba1-dependent manners, as shown in Fig. 2a. To efficiently purify UB-conjugated proteins under denaturing conditions, we constructed lentiviral vectors to express xUB and wt...
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PMC5290280_ncomms14286-f3.png
Uba6 is required for polyubiquitination of the RNA binding protein CUGBP1 and the actin-binding protein ezrin.(a) CUGBP1 and ezrin are polyubiquitinated. HEK293 cells were transfected with polyhistidine-HA-tagged ubiquitin (UB), and treated with 10 μM MG132 for 90 min. The indicated proteins were immunoprecipitated (IP...
Since knowledge about the biological functions of Uba6 is limited, we conducted cell biological characterizations of representative Uba6-specific substrates. We chose the ezrin, radixin and moesin family actin binding protein ezrin2627 and the RNA binding protein CUGBP1 (also known as CELF1) (ref. 28) and attempted to ...
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PMC5290280_ncomms14286-f4.png
Uba6 negatively controls the stability of CUGBP1 and ezrin by mediating K48-linked polyubiquitination of the proteins.(a) Effects of UBA6 silencing by shRNA (shUBA6), overexpression (OE) of Uba6, or Uba6 overexpression in the shUBA6 background (shUBA6+OE) upon the steady-state levels of the indicated proteins. HEK293 a...
Since knowledge about the biological functions of Uba6 is limited, we conducted cell biological characterizations of representative Uba6-specific substrates. We chose the ezrin, radixin and moesin family actin binding protein ezrin2627 and the RNA binding protein CUGBP1 (also known as CELF1) (ref. 28) and attempted to ...
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PMC5290280_ncomms14286-f5.png
Uba6 is required for the regulation of subcellular localization of ezrin and formation of epithelial acini in human nontransformed mammary epithelial MCF-10A cells.(a) Immunofluorescence microscopy for ezrin, F-actin (via phalloidin) and chromosomal DNA (via Hoechst 33342) in cell spheroids formed in 3D culture at day ...
Since ezrin controls apical-basal polarity during epithelial morphogenesis29, we examined whether Uba6-dependent ubiquitination controls acinar morphogenesis using mammary epithelial cells in three-dimensional (3D) culture. MCF-10A cells are non-transformed and undergo differentiation to form highly organized acini-lik...
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PMC5290280_ncomms14286-f6.png
Silencing of ezrin partially rescues UBA6-deficient MCF-10A cells from perturbed epithelial morphogenesis in 3D culture.Human non-transformed mammary epithelial MCF-10A cells stably expressing the indicated shRNAs were generated by lentiviral transduction and drug selection, and examined for epithelial morphogenesis by...
Since ezrin controls apical-basal polarity during epithelial morphogenesis29, we examined whether Uba6-dependent ubiquitination controls acinar morphogenesis using mammary epithelial cells in three-dimensional (3D) culture. MCF-10A cells are non-transformed and undergo differentiation to form highly organized acini-lik...
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PMC3554653_pone.0054647.g001.png
HMGB1 levels in peritoneal dialysis effluents (PDE).(A) Levels of HMGB1 in PDE of patients with or without peritonitis were detected by western blotting. PD patients without peritonitis served as controls (Con). (B) Densitometry of HMGB1 in immunoblots. Data are means ± SE (n = 3), *P<0.05 versus control subjects. (...
To determine whether HMGB1 levels are elevated in PD-related peritonitis, intraperitoneal HMGB1 concentrations were first determined by immunoblot analysis. As shown in Figure 1A and B, the levels of HMGB1 were significantly elevated in PDE samples of patients with peritonitis as compared with the controls. Moreover, l...
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PMC3554653_pone.0054647.g002.png
Serial changes in HMGB1 levels in PDE during peritonitis.(A) Representative HMGB1 immunoblot on PDE samples after antibiotic treatment. (B) Quantitative determination of relative HMGB1 levels in PDE after treatment. Data are expressed as mean ± SE from 3 independent experiments, *P<0.05 versus HMGB1 levels before tr...
To determine whether HMGB1 levels are elevated in PD-related peritonitis, intraperitoneal HMGB1 concentrations were first determined by immunoblot analysis. As shown in Figure 1A and B, the levels of HMGB1 were significantly elevated in PDE samples of patients with peritonitis as compared with the controls. Moreover, l...
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PMC3554653_pone.0054647.g003.png
Levels of TNF-α and IL-6 in PDE during peritonitis.TNF-α levels (A) and IL-6 levels (B) in PDE were measured by ELISA from PD patients with or without peritonitis. The concentrations of TNF-α (C) and IL-6 (D) in PDE among subgroups of patients were determined by ELISA. The values represented the maximum, the third quar...
In parallel analyses, we examined both TNF-α and IL-6 levels in PDE of the first day of peritonitis by ELISA. As shown in Figure 3A and B, levels of TNF-α and IL-6 in PDE of controls were almost undetectable, whereas levels of both cytokines markedly elevated in peritonitis patients. Similarly, PDE levels of TNF-α and ...
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PMC3554653_pone.0054647.g004.png
Correlation between PDE levels of HMGB1 and WBCs as well as cytokines during peritonitis.(A) Correlation between levels of HMGB1 and WBC counts in PDE (r = 0.86, P<0.01). (B) Correlation between levels of HMGB1 and TNF-α in PDE (r = 0.75, P<0.01). (C) Correlation between levels of HMGB1 and IL-6 in PDE (r = 0.81,...
In parallel analyses, we examined both TNF-α and IL-6 levels in PDE of the first day of peritonitis by ELISA. As shown in Figure 3A and B, levels of TNF-α and IL-6 in PDE of controls were almost undetectable, whereas levels of both cytokines markedly elevated in peritonitis patients. Similarly, PDE levels of TNF-α and ...
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PMC3554653_pone.0054647.g005.png
Effects of HMGB1 inhibitor on peritoneal inflammation and function.(A) Representative HE staining showed morphological changes and inflammatory infiltrate in both parietal and visceral peritoneum in each condition. Original magnification×200. (B) The total number of WBCs and the percentage of leukocytes in PDE among di...
Since elevated expression of HMGB1 in PDE was associated with the presence of PD-related peritonitis, we further evaluated whether HMGB1 could play a role in peritoneal function during peritonitis. To this end, acute peritonitis in mice was generated by intraperitoneal injection of LPS as previously described [14]. Com...
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PMC3554653_pone.0054647.g006.png
Effects of LPS on HMGB1 release in HMrSV5 cells.(A) Cells were treated with LPS at various concentrations for 48 hr. Cell culture media were collected and analyzed by immunoblotting with HMGB1 antibody. (B) Densitometry of HMGB1 proteins in immunoblots. (C) Cell viability was evaluated by MTT assay after treatment with...
Given that HMGB1 is released by a variety of activated immune and non-immune cells [16], [17], [18] and peritonitis can cause injury to mesothelial cells, it would be of interest to know whether the elevated HMGB1 in PDE of patients with peritonitis can be directly released from damaged peritoneal mesothelial cells. Be...
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PMC3554653_pone.0054647.g007.png
HMGB1 nuclear-cytoplasmic translocation in LPS-induced HMrSV5 cells.Cells were treated with 2 µg/ml LPS for the indicated time period. (A) Representative confocal microscopic images showed the cellular localization of HMGB1 (red) and nuclear staining (blue) by indirect immunofluorescence staining in cells. Original mag...
Because HMGB1 resides primarily in the nucleus, we further speculated the relocation of HMGB1 from the nucleus to the cytoplasm after LPS treatment. As shown by immunofluorescence, HMGB1 was noted predominantly in the nucleus in the absence of LPS stimulation, but it appeared to move from the nucleus to the cytoplasm b...
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PMC3554653_pone.0054647.g008.png
HMGB1 was secreted via lysosome-mediated secretory pathway in response to LPS stimulation.(A). HMGB1 was present in vesicles cofractionating with lysosomes after LPS administration. Lysosome fractions were untreated (lanes 1 and 2, Try) or solubilized (lanes 3 and 4, TyrTx) with Triton X-100 (TX) before trypsin (Try) d...
HMGB1 shuttles continually from the nucleus to the cytoplasm in quiescent cells [19]. However, HMGB1 lacks a leader peptide and thus not secreted via the Golgi/ER pathway. It has been reported that HMGB1 secretion was mediated by secretory lysosomes in innate immune cells, such as macrophages/monocytes [20]. To test wh...
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PMC3756967_pone.0072088.g001.png
Data and Modelling Overview.The parameters of the sexual contact structure were estimated from the School Health Promotion study [21], FINSEX 2007 study [22], and marriage statistics [23]. The type-specific clearance of new infections was estimated from the control arm of PATRICIA phase III HPV vaccine study in Finland...
For each single hrHPV type, we considered HPV transmission in an “SIRS+V” model, dividing the population into four type-specific epidemiologic states: S for susceptible, I for infectious, R for recovered and V for vaccine-protected individuals. The population was further stratified into behavioural subpopulations. In t...
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PMC3756967_pone.0072088.g002.png
The Pattern of Sexual Contacts in Finland.Upper panel: the age-specific annual mean numbers of new sexual partners by lifetime partner number with the observed numbers (asterisks). Lower panel: the age-specific stratification of the population by lifetime partner number and the corresponding data (asterisks).
The new partner acquisition rate and the corresponding partner number distribution (Figure 2, Figures S1–S3 in File S1) were estimated from the School Health Promotion (SHP) Study 2008–2009 [21], the FINSEX 2007 study [22], and national data on age at marriage [23]. The biannual SHP study covers over half of the 14–18...
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PMC3756967_pone.0072088.g003.png
Transmission Model Structure for a Single HPV Type.The vertical flow corresponds to changes in the epidemiologic states susceptible (S), infectious (I), recovered (R), and vaccine-protected (V). The flow from left to right corresponds to an increasing lifetime partner number (n). The arrows describe possible transition...
Figure 3 presents the structure of the transmission model for a single hrHPV type (for formulae, see Table S4 in File S1). The force of infection was divided into primary and secondary components, according to whether infection is acquired from a new partner or from the current one who has sex with someone else (second...
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PMC3756967_pone.0072088.g004.png
The Age-specific High-risk HPV (hrHPV) Prevalence in the Steady-state Before and After Vaccination.Unless otherwise stated, the results pertain to females under the base-case scenario. (a) The model prediction on the current hrHPV prevalence (upper curve) with the observed data (asterisks). The lower curves show the pr...
The multiple-type transmission model was calibrated to the age-specific all hrHPV prevalence (Figure 4A, Table S6 in File S1) in the hrHPV screening trial [16]. These data include a population-based, non-type-specific, hrHPV prevalence among 75,000 women at screening ages 25, 30, ..., 65 in Finland in the prevaccinatio...
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PMC5410699_12987_2017_61_Fig1_HTML.png
Blood sciences session—Part I. Part I of the blood sciences session focused on the physiology of the blood and neurovascular unit, biofluid-based molecular markers, and extracellular vesicles associated with brain injury and disease progression. The presentations explored how these entities are transported between brai...
Ultrasound has been used in medical applications since the early 1900s and has been used for therapeutic purposes in the CNS since the 1950s. Dr. Mainprize pointed out that more recently, magnetic resonance-guided focused ultrasound (MRgFUS), which is a non-invasive procedure that reversibly opens the BBB without damag...
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Blood sciences session—Part II. Tools and technologies are currently being developed to improve capabilities for assessment and monitoring of CNS trauma to: (1) explore the relationship among the post-traumatic cerebral blood, autoregulation and the neurovascular unit; and (2) leverage different transporters at the BBI...
Exosomes, the smallest (30–150 nm) of cell-derived extracellular vesicles (EVs) are present in all body fluids and serve as carriers of information between tumors, immune cells and normal tissue cells. Dr. Theresa Whiteside presented her research involving exosomes in glioma. Dr. Whiteside noted that genetic and molecu...
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Exosome therapeutics session. Exosomes, the smallest (30–150 nm) type of cell-derived extracellular vesicles, are present in all body fluids and serve as carriers of information across the body in both health and disease. This session focused on the emerging role of exosomes, in particular how they can be harnessed for...
Dr. Robert Clark reported on the importance of membrane transporters at the BBI. These membrane transporters are responsible for efflux of exogenous substrates (e.g. drugs) at the BBB and CSF-blood barriers, impacting the brain’s microenvironment (Fig. 2d). Dr. Clark stressed that many xenobiotics that cross the BBB ar...
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PMC5410699_12987_2017_61_Fig4_HTML.png
Next generation in vitro BBB models session. Next generation BBB models span organ-on-a-chip devices and models exploiting organogenesis, microfluidics, 3D printing, and self-organization. These models are enabled by advances in human brain-specific cell lines and tissue engineering, particularly in 3D co-culture and m...
Dr. William Banks emphasized that the BBB acts as a complex interface regulating the exchange of nutrients, informational molecules, and other substances between the CNS and blood. The properties of this interface are not only due to the physical aspects of the barrier, but also to enzymatic activity and brain-to-blood...
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PMC5410699_12987_2017_61_Fig5_HTML.png
Blood brain barrier delivery and targeting session. Drug delivery through the BBB to the brain can be enhanced utilizing nanoparticles that are designed to exhibit BBB targeting and/or penetrating capabilities. Evidence of these nanoparticles across the BBB can be accessed via in vivo imaging. a Dr. Julia Ljubimova pre...
Advances in computational methods have enabled a new generation of tools for modeling BBB transport. Dr. Martin Ulmschneider described how these models can simulate spontaneous transmembrane diffusion of small molecules using unbiased long timescale atomic detail molecular dynamics (MD) techniques (Fig. 4e) [79–81]. Ac...
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PMC1564397_1475-925X-5-42-1.png
Coronary angiogram of two myocardial bridges in the LAD. (a) Coronary angiogram of two myocardial bridges in the left anterior descending (LAD) branch (arrows) in diastole (left) and systole (right). Compression of the artery during the hearts contraction phase, i.e. systole, is a characteristic finding in myocardial b...
The most common cause of an impaired ability to match oxygen supply and demand is coronary atherosclerosis, a disease that eventually leads to fixed coronary artery lumen narrowing, impaired coronary blood flow and potentially myocardial infarction. However, some people present with chest pain caused by phasic lumen ob...
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PMC1564397_1475-925X-5-42-2.png
Simplified geometry of the myocardial bridge. Schematic anatomy of a double myocardial bridge. The control segments Ωn are equally spaced. Observation locations for haemodynamic properties are in the centre of each segment at xsn, transitions between the segments are at xtn. The transitions length between the segments ...
Theories of longitudinal waves in tubes, with or without non-uniformities, non-linearity and frictional dissipation, are based on the idea that variation of the pressure in an axial cross-section is negligible. If the internal and external pressure along the main flow axis, x, of the artery at time t are given by pint ...
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PMC1564397_1475-925X-5-42-3.png
Deformation cross-section. This figure illustrates the deformation geometry of a circular, linear elastic tube neglecting the bending stress inside the wall. Cross-section B - B (left) shows circular expansion under pressure and the cross-section C - C illustrates the geometry under external deformation (right). The eq...
The two arrows in Figure 2 denote the location of either circular (B - B) or oval (C - C) cross-section of the tube. Due to the fact that the wall thickness, h0, is small compared to the bending radius Rd (h0/Rd ≪ 1), we assume that the bending stress inside the wall is negligible. Consequently the cross-section of a c...
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PMC1564397_1475-925X-5-42-4.png
Deformation function. The variation of the bending radius Rd(xS2, t) in the centre of the deformation is plotted with respect to the cardiac cycle, represented by a EKG trace. The time shift with respect to the cardiac cycle is denoted by Δt, i.e. the solid line has zero time shift, while the dotted and dashed lines ar...
Here Δtn is the time shift for each deformation with respect to the cardiac cycle (see Figure 4) and φm are the phases in radian, chosen to be φ1 = 3.5, φ2 = 1.5, and φ3 = 3.9. The axial curvature of each deformation is approximated by two hyperbolic tangent functions, so that
false
PMC1564397_1475-925X-5-42-5.png
Boundary layer evolution in the myocardial bridge. Illustration of boundary layer separation in a series of two myocardial bridges at a deformation of ζ0 = 0.2; geometry and boundary layer thickness are displayed in realistic proportions, the velocity profiles are schematically drawn. The inflow profile is uniform with...
A schematic illustration of the actual flow profile along the tube axis is shown in Figure 5. We have chosen a uniform inflow profile with velocity V(0, t). The boundary layer (dashed line) grows from the leading edge, decreases in the converging part, while it grows in the divergent part of the tube. The upward triang...
false
PMC1564397_1475-925X-5-42-6.png
Displacement thickness and displacement area in a deformed tube. Illustration of the displacement thickness δ*, the momentum thickness θ and the total displacement thickness δ** in a deformed cross-section. The related areas are the displacement area Aδ* (dark grey), the momentum area Aθ (light grey) and the total disp...
As previously mentioned the surface line of the flat portion of the non-circular duct dominates the circular portion at severe deformations, so that the computation of viscous forces is based on plane wedge flow. Consequently the thickness of the boundary layer is estimated in the xz-plane. Further we assume that the b...
false
PMC1564397_1475-925X-5-42-7.png
Computational domain. Structure of the 27 main segments of the left coronary arteries. The dimensions of a normal anatomic distribution of coronary artery segments are based on 83 angiographies by Dodge et al. [68, 69]. A series of two consecutive myocardial bridges is situated in the mid LAD. In this case we have colo...
Based on 83 angiographies, Dodge et al. [68,69] presented a normal anatomic distribution of coronary artery segments and proposed a terminology, which we used for our model of the left coronary artery (LCA): the left main coronary artery (LMCA) bifurcates into the left anterior descending artery (LAD) and the left circ...
false
PMC1564397_1475-925X-5-42-8.png
Synthetic pressure wave at the inlet. Synthetic pressure wave at the inlet to the left coronary tree are modelled by equation (49). We have chosen the parameters according to measurements in [38]. The baseline (black line), is represented by a stationary pressure ps = 8 kPa and a pressure amplitude of p0 = 7 kPa, while...
where ps is the static pressure and p0 is the amplitude of the exponential waveform, while tr is the rising time. We have chosen the parameters according to measurements in [38]. The baseline condition is represented by a stationary pressure ps = 8 kPa and a pressure amplitude of p0 = 7 kPa, while for the inlet pressur...
false
PMC1564397_1475-925X-5-42-9.png
Spatial dependence of flow variables in a tube with fixed deformation. The area perturbation, flow velocity, pressure and friction coefficient, the wall shear stress, momentum correction factor, the normalised boundary layer thickness and the shape factor are plotted as a function of position in a vessel with fixed def...
The region around the diameter transition in the test geometries is shown in detail in Figure 9. The area perturbation A', shown on the top of each column, indicates that the arterial deformation caused by pulsatile pressure is much smaller in regions where the tube is squeezed (about A'/A = 1 – 2%), while in circular ...
false
PMC1564397_1475-925X-5-42-10.png
Variation of stenosis distance. In columns (a), (b) and (c) we compare a series of two dynamic stenoses, which are separated by one, two and three stenosis dimensions respectively. From the top we illustrate the flow velocity, the pressure, the friction coefficient, the wall shear stress, the momentum correction coeffi...
The region around the diameter transition in the test geometries is shown in detail in Figure 9. The area perturbation A', shown on the top of each column, indicates that the arterial deformation caused by pulsatile pressure is much smaller in regions where the tube is squeezed (about A'/A = 1 – 2%), while in circular ...
false
PMC1564397_1475-925X-5-42-11.png
Temporal evolution of flow variables. The temporal dependence of pressure and volume flow (left) and the separation cycle during deformation (right) of a series of two myocardial bridges are illustrated. The dashed lines represent flow variables in segments with deformation (Ωs2 (red) and Ωs5 (blue)), while solid lines...
Despite the assumption of strong coupling between the boundary layers and the core flow and the assumption of quasi-stationary evolution of the boundary layers, the time dependent motion of the wall under external deformation reproduces some remarkable characteristics of myocardial bridges. In Figure 11 we have shown t...
false
PMC1564397_1475-925X-5-42-12.png
Specific case of clinical relevance. Intracoronary pressure at baseline and during dobutamine challenge. The proximal pressure, pproximal was taken from the inlet of the coronary tree (LMCA), the distal pressure, pdistal in a segment 3 cm distal to the myocardial bridge. At baseline the mean FFR was 0.90, while during ...
The mean pressure drop was calculated by subtracting the average of a distal pressure wave, which was taken approximately 3 cm distal to the myocardial bridge, from the average inlet pressure at the LMCA. The proximal and distal pressure waves for the baseline and while dobutamine challenge are shown in Figure 12. It i...
false
PMC1564397_1475-925X-5-42-13.png
Mean fractional flow reserve in dependence on degree of deformation (left) and segment length (right). The mean pressure derived fractional flow reserve of the baseline environment shown in Figure 8 is plotted as a function of deformation (left) defined in equation (3) and versus the segment length (right). The computa...
In Figure 13 we have shown the coronary pressure-derived fractional flow reserve for the baseline case as a measure of coronary stenosis severity (left) and in dependence on deformation length (right). In both plots we have used baseline inflow conditions with either fixed (solid lines) and dynamic walls (dashed lines)...
false
PMC1564397_1475-925X-5-42-14.png
Pressure drop vs. volume flow. The pressure-drop flow characteristics of stenoses with different degree and extent where obtained under stationary flow conditions. We compare two single dynamic stenosis of length 12 mm (S12) and 24 mm (S24) with a double stenosis with length of 12 mm each (D12). Further D12 is compared...
The pressure-flow relations for different stenotic environments in the coronary arteries are shown in Figure 14. We have applied a stationary flow rate qLMCA at the entrance of the LMCA in the range between 4.5 cm3/s and 9 cm3/s. The resultant mean flow in the myocardial bridge, qMB was between 1.57 cm3/s and 3.13 cm3/...
false
PMC1564397_1475-925X-5-42-15.png
Influence of the wall velocity on boundary layer thickness, friction coefficient and wall shear stress. The bottom figure shows the normalised thickness of the boundary layer during in- (left) and outward motion (right) of the wall in the dynamic configuration presented in the third Additional file. Compared to zero wa...
In contrast to fixed stenoses, the velocity of the wall νw ≠ 0 in a dynamic environment, i.e. positive during compression and negative while the vessel is relaxing. At the bottom of Figure 15 we have shown the thickness of the boundary layer during inward (left) and outward motion (right) of the wall compared to fixed ...
false
PMC4928054_srep28997-f1.png
(A) Circulating levels of anti-dsDNA antibody in WT and Psgl-1−/− mice treated with PBS or pristane for 32 weeks (n = 8 mice per group). (B) Circulating levels of anti-snRNP antibody in WT and Psgl-1−/− mice treated with PBS or pristane for 32 weeks (n = 8 mice per group). (C) Urine albumin/creatinine ratios of WT (n =...
Pristane has previously been shown to induce nephritis in C57BL/6J mice characterized by glomerular proliferation, mesangial expansion, and proteinuria1718. These changes are associated with elevated levels of anti-dsDNA antibodies. Consistently, we observed increased anti-dsDNA antibodies in pristane-treated mice comp...
false
PMC4928054_srep28997-f2.png
Glomerular histopathology in WT and Psgl-1−/− mice treated with pristane or PBS for 32 weeks (n = 8 mice per group).(A–D) Representative glomeruli stained with Periodic Acid-Schiff (PAS) from control WT (A), pristane-treated WT (B), control Psgl-1−/− (C), and pristane-treated Psgl-1−/− mice (D). Glomeruli from pristane...
To determine the effect of Psgl-1 deficiency on nephritis in this model of lupus, kidney sections stained with PAS were scored by histopathology using both activity and chronicity indices that approximate the scoring system of human lupus nephritis. Both activity and chronicity were significantly increased in both pris...
true
PMC4928054_srep28997-f3.png
Measurements of circulating biomarkers in WT and Psgl-1−/− mice treated with PBS or pristane for 32 weeks (n = 8 mice per group).(A) Levels of chemokine (C-X-C motif) ligand 1 (CXCL1). (B) Levels of monocyte chemoattractant protein-1 (MCP-1). (C) Levels of chemokine (C-C motif) ligand 3 (CCL3). (D) Levels of interleuki...
To determine the effect of pristane on a circulating inflammatory biomarkers potentially involved in leukocyte recruitment, the plasma levels of CXCL1, IL-6, CCL3, and MCP-1 were measured in PBS-treated or pristane-treated mice. 32 weeks after treatment, levels of CXCL1 (Fig. 3A), MCP-1 (Fig. 3B), and CCL3 (Fig. 3C) we...
false
PMC4928054_srep28997-f4.png
Ischemic stroke in WT and Psgl-1−/− mice treated with PBS or pristane for 32 weeks (n = 8 mice per group).(A–D) Representative brain slides stained with TTC from control WT (A), pristane-treated WT (B), control Psgl-1−/− (C), and pristane-treated Psgl-1−/− mice (D). (E) Quantification of infarct area expressed as a per...
To determine if pristane-treated Psgl-1−/− mice were protected from acute tissue injury, the effect of Psgl-1 deficiency in a model of acute ischemic stroke was determined. Stroke was induced by photochemical-mediated injury to the MCA which leads to sustained thrombotic occlusion of the MCA1324. Following MCA occlusio...
true
PMC4928054_srep28997-f5.png
Neutrophil infiltration after stroke examined by myeloperoxidase (MPO) staining of cerebral infarct area from WT and Psgl-1−/− mice treated with PBS or pristane for 32 weeks (n = 8 mice per group).(A–D) Representative photomicrographs of MPO staining in brain cross sections from control WT (A), pristane-treated WT (B),...
Ischemic stroke is characterized by increased inflammatory cell infiltration, which exacerbates cerebral infarction25. To assess inflammatory cell recruitment in lupus mice after stroke, neutrophils were detected 3 days following stroke induction. Neutrophil infiltration was significantly increased in the infarct area ...
true
PMC4928054_srep28997-f6.png
Macrophage infiltration after stroke examined by Mac-3 staining at cerebral infarct area of WT and Psgl-1−/− mice treated with PBS or pristane for 32 weeks (n = 8 mice per group). (A–D) Representative photomicrographs of Mac-3 staining in brain cross sections from control WT (A), pristane-treated WT (B), control Psgl-1...
Ischemic stroke is characterized by increased inflammatory cell infiltration, which exacerbates cerebral infarction25. To assess inflammatory cell recruitment in lupus mice after stroke, neutrophils were detected 3 days following stroke induction. Neutrophil infiltration was significantly increased in the infarct area ...
true
PMC3458939_1746-4811-8-25-1.png
Design for performingin vivoBiFC screens by DNA transfection in protoplasts. The screen design is explained in detail in the text. In brief, DNA from a random library and specific bait are co-transfected into protoplasts. Protoplasts providing positive BiFC signals are identified and sorted by FACS. The DNA is harveste...
The novel in planta protein-protein library screen using BiFC technology is depicted in Figure1. The screen is based on recovering plasmid DNA from a random, plasmid encoded cDNA library that has been transfected along with a bait plasmid into living plant protoplasts. Protein interactions are observed in whole cells b...
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PMC3458939_1746-4811-8-25-2.png
Detection sensitivity of YFP fusion proteins. We tested our cytometer for its detection sensitivity of different protein fusions. One can see from comparison with the mock negative control, that YFP expressing protoplasts can be clearly identified as a cloud of cells shifted to the right in the FL1 channel. A. Mock tra...
BiFC fluorescence signals are known to be less bright compared to non-truncated mYFP [15]. Therefore, full-length YFP and YFP derived BiFC signals were tested to ascertain the detection limit of our FACS system (Figure2). We tested previously described proteins as full length protein–mYFP fusions. Besides testing well-...
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PMC3458939_1746-4811-8-25-3.png
Screening controls for the YN-cDNA and YC-cDNA libraries. X-axis is YFP fluorescence and Y-axis is autofluorescense; arrows show and indicate positive mYFP-BiFC signals. A. Mock transfected cells. B. Cells transfected with YN-Library alone. C. Cells transfected with free YN fragment alone. D. Cells co-transfected with ...
BiFC interactions are purported to be irreversible [7] and require many tests to control for spontaneous association of the YFP fragments [15]. Techniques designed for reducing non-specific background in confocal set-ups [15] were not suitable for designing this screen to capture rare, weak signals. Therefore we used b...
false
PMC3458939_1746-4811-8-25-4.png
Cytometric and plasmid recovery results from the CPK3 screen. Panels A- D show typical results of observing 2 x 105 to 4 x 105 events; more than 2.5 x 106 events were analyzed per FACS session. A. Mock transfected (water only), B.CPK3-YN173 transfected alone (no YFP signal is produced), C. First Round, initial co-trans...
The screen with bait CPK3-YN173 was conducted according to Figure1. The CPK3-YN173 fusion was negative for self-complementation (figure3K, 4A). Furthermore, BiFC signals were detected in the protoplast population, when CPK3-YN173 was co-transformed with the YC-cDNA library. 2.5 x 106 transfected protoplasts were screen...
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PMC3458939_1746-4811-8-25-5.png
Cytometric plots of testing for BIFC between bait CPK3-YN173 and fished YC fusion proteins.A. Cytometric plots are shown from the second round screening that lead to 8 positive colonies (3 were eliminated due to technical difficulties, see text). B. Subsequent testing of the 8 candidate proteins after re-cloning of the...
The screen with bait CPK3-YN173 was conducted according to Figure1. The CPK3-YN173 fusion was negative for self-complementation (figure3K, 4A). Furthermore, BiFC signals were detected in the protoplast population, when CPK3-YN173 was co-transformed with the YC-cDNA library. 2.5 x 106 transfected protoplasts were screen...
false
PMC3458939_1746-4811-8-25-6.png
Results of FRET-FLIM measurements of CPK3 with candidate interaction proteins.A. Example expression domains of CPK3-eGFP and mRFP-XP fusion proteins as seen in tobacco epidermal cells. B. Comparison of the localization pattern of APX3 with either an N-terminal mRFP fusion (left) or a C-terminal mCherry fusion (right). ...
The colony number as in Figure5A is given for consistency along with the gene AGI identifier and common name of the plasmid predominately present in the plasmid prep. The dominate cDNA sequence was re-cloned from fresh Arabidopsis cDNA for confirmatory BiFC (data in Figure5B, C) and FRET-FLIM experiments (data in Figur...
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PMC4816561_pntd.0004559.g001.png
Microphotograph of a thick blood smear of the patient at the time of admission.The image shows spirochetes together with leucocytes. Striking is the relative short length of the bacterial cells (10μm) and the relative small number of turns. This morphology was observed in all intact bacteria in the slide. Pictures were...
The medical history of the patient was significant for a pelvic vein thrombosis with subsequent pulmonary embolism in 2003. Hypercoagulability due to antithrombin III deficiency was diagnosed and pharmacological long-term therapy with phenprocoumon daily was initiated. There are no other medical conditions known in the...
true
PMC4816561_pntd.0004559.g002.png
Molecular phylogenetic analysis using the maximum likelihood method based on partial sequences of (A) 16S rRNA (473 bp), (B) flaB (694 bp) and (C) uvrA (900 bp). The taxa labels show the NCBI accession number, Borrelia species, and strain information (if available). The strain investigated in this study (indicated by a...
In BLAST searches using 16S rRNA and flaB PCR sequences top hits included B. anserina as well as New World relapsing fever species such as B. parkeri and B. hermsii. Genetic distance analyses conducted in MEGA revealed a value of 0.004 compared to strain VS4 from Tanzania (for which the 16S rRNA sequence was available ...
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PMC4696535_jptm-2015-10-23f1.png
Spiral artery changes during pregnancy. (A) Normal physiologic transformation of spiral arteries in a normal pregnancy. The lumen of the spiral artery (asterisks) is dilated. Trophoblastic cells are infiltrating the wall of the spiral artery. (B) Failure of physiologic transformation of spiral arteries in a patient wit...
Normal physiologic transformation of the uterine spiral arteries during early pregnancy is considered a foundation of successful pregnancy [58]. The spiral arteries are normally transformed into large dilated vessels, with dramatic structural changes to the vessel wall. The key findings of normal transformation of the ...
true
PMC4696535_jptm-2015-10-23f2.png
Acute atherosis in decidual spiral arteries. (A) Many lipid-laden macrophages (arrows) are seen in the spiral arteries. (B) Acute atherosis on oil-red O staining. Fat droplets (arrows) in the non-transformed spiral artery are stained red.
Histologic findings of acute atherosis consist of the presence of fibrinoid necrosis of the artery wall, a subendothelial collection of lipid-laden macrophages, and vascular or perivascular lymphocytic infiltration in non-transformed uterine spiral arteries (Fig. 2A) [1,11]. Lipids in the spiral arteries with acute ath...
true
PMC2848590_pone.0009949.g001.png
Map showing locations of cruises and material collected in this study.
Chaetognaths sequenced in this project were collected on six cruises (Figure 1). A cruise collected zooplankton from the waters west of the Antarctic Peninsula on board the R/V N.B. Palmer in 2002 (NBP0202). Four cruises sampled waters in the Atlantic: the R/V G.O. Sars to the northern Mid-Atlantic Ridge (MAR) in summe...
false
PMC2848590_pone.0009949.g002.png
Hierarchical histograms of pairwise Kimura 2-Parameter (K2P) distances between specimens.Vertical lines show mean pairwise distance at each level. Asterisks mark outlier values discussed in the Results. A, K2P distances within species. B, K2P distances between species within each genus.
Hierarchical comparison of K2P distances at different taxonomic levels revealed disjunct distributions in sequence similarity within vs. between species (Figure 2A,B). The average proportion of difference in sequences within species was 0.0146±0.0193 (mean±SD), whereas mean distance between species within a genus was o...
false
PMC2848590_pone.0009949.g003.png
Gene tree for COI, showing topology and branch lengths from Bayesian analysis.Pairs of numbers in parentheses are support values, given as (Bayesian posterior probabilities, approximate Likelihood Ratio Test support), with asterisks indicating maximum support of (1.00, 1.00), and blanks indicating topologies not recove...
The optimal gene trees produced by Bayesian and ML searches showed nearly identical topology, in which the tip branches within species were short, and species were separated by much longer branches (Figure 3). Sequences clustered strongly by species in all cases. Although the nodes separating Sagitta spp. from all othe...
false
PMC4147877_1556-276X-9-402-1.png
Setup of arc discharge decomposition process.
In Figure 1, the complete experimental setup for carbon film fabrication has been demonstrated.
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PMC4147877_1556-276X-9-402-2.png
TTT electrode configuration (a) before arc discharge decomposition, (b) carbon film obtained.
Once the arc discharge is initiated, methane decomposition starts causing the resultant carbon atoms to deposit and stack up between the two electrodes creating a conductive bridge. The growth time was measured to be 11.6 s at the voltage of 16.4 kV. The carbon film fabricated in this process is inspected using high-re...
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PMC4147877_1556-276X-9-402-3.png
SEM image of a sample. Imaging mode (a) × 370 at 15 kV, (b) × 1,500 at 10 kV, (c) × 4,000 at 15 kV, and (d) × 14,000 at 10 kV.
A scanning electron microscope (SEM) scans the samples with a focused beam of electrons. As the electrons collide with the atoms in the sample, they produce various signals which can be detected and measured [18]. These signals provide information about the surface topography and composition of the sample. Microphotogr...
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PMC4147877_1556-276X-9-402-4.png
OES spectrum of first phase of evolved species of methane.
The optical emission during arc discharge decomposition was captured in the wavelengths ranging from 385 to 750 nm through a spectrophotometer (StellarNet, Tampa, FL, USA), and the data of the recorded spectra was sketched using MATLAB software. Three evolved peaks of methane species were prominent which belong to CH, ...
false
PMC4147877_1556-276X-9-402-5.png
OES spectrum of second phase of evolved species of methane.
The optical emission during arc discharge decomposition was captured in the wavelengths ranging from 385 to 750 nm through a spectrophotometer (StellarNet, Tampa, FL, USA), and the data of the recorded spectra was sketched using MATLAB software. Three evolved peaks of methane species were prominent which belong to CH, ...
false
PMC4147877_1556-276X-9-402-6.png
Electrical measurement setup for the carbon film grown between different electrode configurations.
Once the carbon film was produced, a series of low DC voltage measurements were conducted on them in order to reveal their actual current-voltage characteristics. To do this, a DC power supply was employed to apply low voltage to the two electrodes and the carbon film in between. Figure 6 provides a schematic of the el...
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PMC4147877_1556-276X-9-402-7.png
I-V characteristics of carbon film. (a) Before gas exposure, (b) under 200 ppm gas, (c) under 400 ppm gas, (d) under 800 ppm gas, (e) all experimental tests.
After growing the carbon film, both sides of the chamber must be opened to release the methane gas inside it. After about 20 min, when there is almost no gas present in the chamber, we start to apply the DC voltage and measure the resulting I-V characteristics. The measurements were repeated in the presence of gas with...
false
PMC2867803_1743-422X-7-83-1.png
Analysis of hydrophilicity and antigenic index of DPV UL46 protein. The hydrophilicity and antigenic index of DPV UL46 protein were analyzed by DNAstar6.0. Then the main antigen regions UL46M was selected on the basis of the analysis result and was expressed with the complete UL46 gene.
Generally, the expression of the main antigenic regions of the protein was prioritized in order of increasing immunogenicity and specificity of the corresponding antibody. Therefore, we analyzed the hydrophilic and antigenic indices of UL46 and selected 507 amino acids (site, 233-739) (Figure 1) as the main antigenic r...
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PMC2867803_1743-422X-7-83-2.png
PCR products of the fragments of DPV UL46M and UL46M gene. Lane 1, PCR product of DPV UL46; Lane M, DNA marker; Lane 2, PCR product of DPV UL46M.
Two regions of DPV, approximately 2,500 bp and 1,500 bp in UL46 and UL46M, respectively, were amplified by PCR (Figure 2, lane 1 and lane 2). The PCR products were digested with BamHI and XhoI restriction enzymes and the open reading frames (ORFs) were inserted into the pMD18-T vector to construct the cloning vectors p...
false
PMC2867803_1743-422X-7-83-3.png
DPV UL46 and UL46M gene encoding DNA sequences were cloned into pMD18-T cloning vector. The recombinant plasmids were digested with two restriction enzymes. Lane 1, BamHI and XhoI generating two restriction fragments of UL46M; Lane M, DNA marker; Lane 2, BamHI and XhoI generating two restriction fragments of UL46.
Two regions of DPV, approximately 2,500 bp and 1,500 bp in UL46 and UL46M, respectively, were amplified by PCR (Figure 2, lane 1 and lane 2). The PCR products were digested with BamHI and XhoI restriction enzymes and the open reading frames (ORFs) were inserted into the pMD18-T vector to construct the cloning vectors p...
false
PMC2867803_1743-422X-7-83-4.png
A. DPV UL46 and UL46M gene encoding DNA sequences were cloned into pET32a (+) procaryotic expression vector. The recombinant plasmids were digested with two restriction enzymes. Lane 1, BamHI and XhoI generating two restriction fragments of UL46; Lane M, DNA marker; Lane 2, BamHI and XhoI generating two restriction fra...
The UL46 and UL46M gene fragments were subcloned from pMD18-T/UL46 and pMD18-T/UL46M into the prokaryotic expression vector pET32a(+) using BamHI and XhoI and were confirmed by restriction enzyme analysis (Figure 4a, lane 1 and lane 2). The newly formed vectors were designated pET32a(+)/UL46 and pET32a(+)/UL46M, respec...
false
PMC2867803_1743-422X-7-83-5.png
A. Detection of DPV by Dot-ELISA. The preliminary application of the polyclonal antibody against DPV UL46M was the establishment of Dot-ELISA to detect DPV. The result showed stronger positive signal with the liver sample of DPV, while negative with DHV-1, E. coli (O1), SE, RA, P. multocida and normal saline. 1. DPV, 2...
The preliminary application of the polyclonal antibody against DPV UL46M was in the detection of DPV by Dot-ELISA. Thus, the samples were prepared on a nitrocellulose (NC) membrane and the anti-UL46M IgG and HRP-labeled goat anti-rabbit IgG antibodies were used for DPV detection. The square matrix test determined that ...
false
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MedPMC Initial Screening Training/Test Datasets

Overview

This dataset contains the annotations used for the initial screening stage of the MedPMC framework, which aims to identify clinically relevant medical images from biomedical literature. The training and validation sets are automatically curated using GPT-4o. The test set is manually annotated. For details on dataset construction, annotation guidelines, and the overall MedPMC pipeline, please refer to our paper.

Dataset Statistics

Split Samples
Train 39,360
Validation 9,781
Test 600

Dataset Features

Field Description
image Image path
image_id Unique image identifier
caption Figure caption
reference_text Concatenated paragraphs from the article that reference the figure.
is_medical Binary label indicating whether the figure is a clinically relevant medical image

Quick Start

Load the Dataset

from datasets import load_dataset

dataset = load_dataset("Yale-BIDS-Chen/medpmc-screening-dataset")

print(dataset)

Access a Sample

sample = dataset["train"][0]

print(sample["image_id"])
print(sample["caption"])
print(sample["reference_text"])
print(sample["is_medical"])

Display an Image

sample = dataset["train"][0]

image = sample["image"]
image.show()
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