gebhart/patrepeval huggingface dataset:
Antibacterial Evaluation of Synthetic Thiazole Compounds In Vitro and In Vivo in a Methicillin-Resistant Staphylococcus aureus (MRSA) Skin Infection Mouse Model (2015)

The emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA), including strains resistant to current antibiotics, has contributed to an increase in the number of skin infections reported in humans in recent years. New therapeutic options are needed to counter this public health challenge. The aim of the present study was to examine the potential of thiazole compounds synthesized by our research group to be used topically to treat MRSA skin and wound infections. The broth microdilution method confirmed that the lead thiazole compound and four analogues are capable of inhibiting MRSA growth at concentrations as low as 1.3 μg/mL. Additionally, three compounds exhibited a synergistic relationship when combined with the topical antibiotic mupirocin against MRSA in vitro via the checkerboard assay. Thus the thiazole compounds have potential to be used alone or in combination with mupirocin against MRSA. When tested against human keratinocytes, four derivatives of the lead compound demonstrated an improved toxicity profile (were found to be non-toxic up to a concentration of 20 μg/mL). Utilizing a murine skin infection model, we confirmed that the lead compound and three analogues exhibited potent antimicrobial activity in vivo, with similar capability as the antibiotic mupirocin, as they reduced the burden of MRSA present in skin wounds by more than 90%. Taken altogether, the present study provides important evidence that these thiazole compounds warrant further investigation for development as novel topical antimicrobials to treat MRSA skin infections.
Prostate Cancer Screening — A Perspective on the Current State of the Evidence (2017)

Controversy continues to roil around the role of PSA screening in prostate cancer. The authors review the available data and its quality and conclude that the evidence does not indicate that the benefits outweigh the harms.
A Possible Relation of the Helicobacter pylori pfr Gene to Iron Deficiency Anemia? (2001)

The mutation in the pfr gene did not relate with the clinical phenotype, iron deficiency anemia. Further studies are needed on the aspects of host side or other complex factors to elucidate the mechanisms by which the H. pylori infection might lead to iron deficiency anemia.
Lung Volume and Continuous Positive Airway Pressure Requirements in Obstructive Sleep Apnea (2005)

Previous studies have demonstrated that lung volume during wakefulness influences upper airway size and resistance, particularly in patients with sleep apnea. We sought to determine the influence of lung volume on the level of continuous positive airway pressure (CPAP) required to prevent flow limitation during non-REM sleep in subjects with sleep apnea. Seventeen subjects (apnea-hypopnea index, 42.6 +/- 6.2 [SEM]) were studied during stable non-REM sleep in a rigid head-out shell equipped with a positive/negative pressure attachment for manipulation of extrathoracic pressure. An epiglottic pressure catheter plus a mask/pneumotachometer were used to assess flow limitation. When lung volume was increased by 1,035 +/- 22 ml, the CPAP level could be decreased from 11.9 +/- 0.7 to 4.8 +/- 0.7 cm H(2)O (p < 0.001) without flow limitation. The decreased CPAP at the same negative extrathoracic pressure yielded a final lung volume increase of 421 +/- 36 ml above the initial value. Conversely, when lung volume was reduced by 732 +/- 74 ml (n = 8), the CPAP level had to be increased from 11.9 +/- 0.7 to 17.1 +/- 1.0 cm H(2)O (p < 0.001) to prevent flow limitation, with a final lung volume decrease of 567 +/- 78 ml. These results demonstrate that relatively small changes in lung volume have an important effect on the upper airway in subjects with sleep apnea during non-REM sleep.
Synthesis and Structure−Activity Relationship Exploration of Carbon-Supported PtRuNi Nanocomposite as a CO-Tolerant Electrocatalyst for Proton Exchange Membrane Fuel Cells (2006)

A carbon-supported PtRuNi nanocomposite is synthesized via a microwave-irradiated polyol plus annealing synthesis strategy. The catalyst is characterized by transmission electron microscopy, powder X-ray diffraction, energy dispersive spectroscopy, and X-ray photoelectron spectroscopy. The data are discussed with respect to those for the carbon-supported PtRu nanocomposite prepared following the same way. The characterizations show that the inclusion of Ni in the PtRu system has only a small effect on the particle size, the structure, and the compositional homogeneity. CO-stripping voltammetry and measurements on the single proton exchange membrane fuel cells show that the PtRuNi/C catalyst has an improved activity for CO(ads) electro-oxidation. An accelerated durability test on the catalyst exhibits insignificant loss of activity in acidic media. On the basis of the exploration of the structure-activity relationship, a mechanism for the improved performance of the catalyst is proposed. It is suggested that the improved CO-tolerant performance of the PtRuNi/C nanocomposite should be related to the hydrogen spillover on the catalyst surface, the enhanced oxidation of CO(ads) by nickel hydroxides, and the high proton and electronic conductivity of the hydroxides. The nickel hydroxide passivated surface and/or anchoring of metallic nickel in the platinum lattice may contribute to the durability of the catalyst in acid solution.
Formation of the flavivirus envelope: role of the viral NS2B-NS3 protease (1995)

One of the late processing events in the flavivirus replication cycle involves cleavage of the intracellular form of the flavivirus capsid protein (Cint) to the mature virion form (Cvir) lacking the carboxy-terminal stretch of hydrophobic amino acids which serves as a signal peptide for the downstream prM protein. This cleavage event was hypothesized to be effected by a viral protease and to be associated with virion formation. We have proposed a model of flavivirus virion formation in which processing of the C-prM precursor at the upstream signalase site is upregulated by interaction of the NS2B part of the protease with the prM signal peptide or with an adjacent carboxy-terminal region of the capsid protein in the precursor, and processing of Cint by the NS2B-NS3 protease follows the signalase cleavage. Recently, an alternative hypothesis was proposed which suggests a reverse order of these two cleavage events, namely, that cleavage of the C-prM precursor by the NS2B-NS3 protease at the Cint-->Cvir dibasic cleavage site is a prerequisite for the subsequent signalase cleavage of the prM signal peptide. To distinguish between these alternative models, we prepared a series of expression cassettes carrying mutations at the Cint-->Cvir dibasic cleavage site and investigated the effects of these mutations on signalase processing of C-prM and on formation and secretion of prM-E heterodimers. For certain mutated C-prM precursors, namely, for those with Lys-->Gly disruption of the dibasic site, efficient formation of prM was observed upon expression from larger cassettes encoding the viral protease, despite the absence of processing at the Cint-->Cvir cleavage site. Surprisingly, formation and secretion of prM-E heterodimers accompanied by late cleavage of prM was also observed for these cassettes, with an efficiency comparable to that of the wild-type expression cassette. These observations contradict the model in which cleavage of the C-prM precursor at the Cint-->Cvir dibasic site is a prerequisite for signalase cleavage.
Example-based Automatic Portraiture (2002)

In this paper, we present an example-based approach for automatically generating a life-like portrait from a frontal face image. Based on an inhomogeneous Markov Random Field Model, an inhomogeneous non-parametric sampling scheme is used to capture the complex statistical characteristics of face image and corresponding portrait. In our approach, only those pixels corresponding to a portrait point are sampled. Such a strategy is crucial for maintaining facial structure and guaranteeing coherence of portrait lines. Experimental results demonstrate the effectiveness and lifelikeness of our approach. 1
Human lymphotoxin has at least equal antitumor activity in comparison to human tumor necrosis factor but is less toxic in mice (1995)

Because of the severe toxicity of systemically applied tumor necrosis factor (TNF) in cancer patients, considerable efforts have been made to construct mutant TNF molecules, which retain antitumor activity, but display less toxicity. We compared tumor suppression in relation to the toxic effects of human TNF and human lymphotoxin (LT) in mice. The genes for these two cytokines were expressed in Chinese hamster ovary (CHO) cells. Intraperitoneal injection of parental and gene modified CHO cell lines producing similar amounts of biologically active TNF or LT, respectively, into nude mice showed that CHO-TNF cells killed the mice more rapidly than parental cells, but that CHO-LT tumor bearing mice lived significantly longer than mice injected with parental cells. Injection of the cells subcutaneously into severe combined immunodeficiency (SCID) mice allowed direct comparison of tumor suppression and toxic effects of the two cytokines. Both TNF and LT produced by the tumor effectively suppressed tumor growth by an indirect mechanism, LT being at least as effective as TNF. However, mice bearing CHO-TNF cells either died rapidly or developed cachexia, as shown by weight loss. In contrast, mice injected with CHO-LT cells never rapidly died and became cachectic much later than CHO-TNF cell injected animals, though serum levels of LT were higher than those of TNF. Analysis of soluble forms of TNF receptors (TNF-R1 and TNF-R2) in sera of tumor bearing mice showed that soluble TNF-R1 was downregulated in both CHO-TNF and CHO-LT, in comparison with CHO-neo cell injected mice and to normal SCID mice. The soluble form of TNF-R2 was induced by CHO cell lines. In CHO-TNF cell injected SCID mice, serum levels were significantly increased, whereas in mice injected with CHO-LT cells, serum levels of soluble TNF-R2 were decreased. Together, our results show a higher therapeutic index of LT compared with TNF.
Toward tetherless insufflation of the GI Tract (2010)

Toward increasing the diagnostic ability of wireless capsule endoscopy, we propose a method to wirelessly insufflate the Gastrointestinal Tract. By increasing the viewable surface area, it appears likely that capsule-based insufflation may reduce the number of false negative diagnoses made by endoscopic capsules. Our approach to wireless insufflation is to utilize controlled phase transition of a small volume of fluid stored onboard the capsule to a large volume of gas that is then emitted into the intestine. We begin by describing experiments designed to evaluate the amount of gas a capsule must produce to have a beneficial impact on visualization in the colon. We then describe experiments evaluating how much gas can be generated from a given volume of fluid, using Hydrogen Peroxide as our working fluid. We also evaluate thermal effects of the Hydrogen Peroxide reaction. The cumulative result of these experiments is an illustration of the feasibility of carrying a sufficient volume of fluid onboard a wireless capsule to generate a beneficial enhancement in visualization of the interior of the Gastrointestinal Tract, and specifically the colon.
Macrophage heterogeneity in the rat as delineated by two monoclonal antibodies MRC OX-41 and MRC OX-42, the latter recognizing complement receptor type 3. (1986)

Two monoclonal antibodies, designated MRC OX-41 and MRC OX-42, have been shown to label subsets of macrophages. Using immunoperoxidase and immunofluorescence analysis, tissue macrophages were shown to be heterogeneous with respect to binding of MRC OX-41 and MRC OX-42 antibodies. Although both antibodies labelled subsets of macrophages, the antibodies also reacted with granulocytes and dendritic cells. The antigens recognized by these antibodies were identified by metabolic and cell surface labelling followed by immunoprecipitation and sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE). MRC OX-41 recognized a surface protein of 110,000-120,000 MW, while MRC OX-42 immunoprecipitated three polypeptides with molecular weights of 160,000, 103,000 and 95,000. The Fab fragment of MRC OX-42 antibody inhibited complement-mediated rosette formation between sensitized erythrocytes and rat macrophages and granulocytes. Membrane molecules with similar biochemical and functional properties to MRC OX-42 antigen have been identified in mouse and man as the receptors for iC3b, and it is probable that MRC OX-42 antibody recognizes the rat homologue of the receptors in these other species.
Computational deconvolution of transcriptomics data from mixed cell populations (2018)

Supplementary data are available at Bioinformatics online.
Characterization of the Extracellular Domain in Vascular Endothelial Growth Factor Receptor‐1 (Flt‐1 Tyrosine Kinase) (1997)

Flt-1 tyrosine kinase, vascular endothelial growth factor (VEGF) receptor-1, binds VEGF and a new VEGF-related ligand, placenta growth factor, but KDR/Flk-1 (VEGF receptor-2) binds only VEGF. To characterize the functional regions in the Flt-1 extracellular domain such as the ligand binding region and the dimer formation of the receptor, we constructed a series of mutants of the Flt-1 extracellular domain as soluble forms in a baculovirus system. We found that a region carrying the N-terminal 1st to 3rd immunoglobulin (Ig)-like domains of Flt-1 binds both ligands with high affinity. However, for dimer formation of soluble Flt-1, a region further downstream in the Flt-1 extracellular domain was required. Mutant Flt-1 receptors expressed in COS cells confirmed the requirement of the 4th to 7th Ig region for the activation of Flt-1 tyrosine kinase. Soluble Flt-1 carrying the N-terminal 1st to 3rd Ig region suppressed VEGF-dependent endothelial proliferation in vitro to the same level as the larger forms of soluble Flt-1, suggesting that the binding of one soluble Flt-1 molecule to one subunit of the VEGF homodimer may be sufficient to block the VEGF activity.
Generation of Recombinant Multimeric Antibody Fragments for Tumor Diagnosis and Therapy (2003)

Single chain recombinant antibody fragments can multimerise to provide high binding avidity and unique specificity for target antigens and can be used to replace the parent antibody or Fab derivatives (1). A unique advantage in using bacterial expression systems is the high yield and low cost, especially when the VH and VL domains are tethered by a single-chain linker (scFv). This chapter describes expression systems for production of new types of scFv molecules with size, flexibility, and valency suited to in vivo cell-targeting, tumor imaging, and therapy. Further, we review the design of expression cassettes that create multi-specific scFv dimers suited to crosslinking target antigens for T-cell recruitment, viral delivery, and immunodiagnostics. Choice of the linker length that joins VH and VL domains dictates precisely whether the (scFv) product is a soluble monomer or a high-avidity multimer (dimer, trimer, etc.). Based on the Kabat numbering system (2) and X-ray structures of Fv domains (3,4), we define the C-terminal end of the VH domain as SerH112 or ArgL107 of VL. In either VH-VL or VL-VH orientation, single chain Fv fragments (scFvs, ≈30 kDa) are predominantly monomeric when the Fv domains are joined by polypeptide linkers of at least 12 residues (5). An scFv molecule with a linker of 3–12 residues cannot fold into a functional Fv domain and instead associates with a second scFv molecule to form a bivalent dimer (diabody, ≈60 kDa) (5,6). Reducing the linker length below three residues can force scFv association into trimers (triabodies, ≈90 kDa) or tetramers (≈120 kDa) depending on linker length, composition, and Fv domain orientation (7–10). The increased binding valency in these scFv multimers results in high avidity (long off-rates). A particular advantage for tumor targeting is that molecules of ≈60–100 kDa have increased tumor penetration and fast clearance rates compared to the parent Ig (150 kDa) (1,11–14). A number of cancer-targeting scFv multimers have recently undergone preclinical evaluation for in vivo stability and efficacy (11–14). Bi- and tri-specific multimers can be formed by association of different scFv molecules and, in the first examples, have been designed as crosslinking reagents for T-cell recruitment into tumors (immunotherapy) and as red blood cell agglutination reagents (immunodiagnostics) (1,15,16).
Large-area graphene-nanomesh/carbon-nanotube hybrid membranes for ionic and molecular nanofiltration (2019)

Nanoporous two-dimensional materials are attractive for ionic and molecular nanofiltration but limited by insufficient mechanical strength over large areas. We report a large-area graphene-nanomesh/single-walled carbon nanotube (GNM/SWNT) hybrid membrane with excellent mechanical strength while fully capturing the merit of atomically thin membranes. The monolayer GNM features high-density, subnanometer pores for efficient transport of water molecules while blocking solute ions or molecules to enable size-selective separation. The SWNT network physically separates the GNM into microsized islands and acts as the microscopic framework to support the GNM, thus ensuring the structural integrity of the atomically thin GNM. The resulting GNM/SWNT membranes show high water permeance and a high rejection ratio for salt ions or organic molecules, and they retain stable separation performance in tubular modules.
Biodegradable polymer/hydroxyapatite composites: Surface analysis and initial attachment of human osteoblasts (2001)

Biodegradable polymer/hydroxyapatite (HA) composites have potential application as bone graft substitutes. Thin films of polymer/HA composites were produced, and the initial attachment of primary human osteoblasts (HOBs) was assessed to investigate the biocompatibility of the materials. Poly(epsilon-caprolactone) (PCL) and poly(L-lactic acid) (PLA) were used as matrix materials for two types of HA particles, 50-microm sintered and submicron nonsintered. Using ESEM, cell morphology on the surfaces of samples was investigated after 90 min, 4 h, and 24 h of cell culture. Cell activity and viability were assessed after 24 h of cell culture using Alamar blue and DNA assays. Surface morphology of the polymer/HA composites and HA exposure were investigated using ESEM and EDXA, respectively. ESEM enabled investigation of both cell and material surface morphology in the hydrated condition. Combined with EDXA it permitted chemical and visual examination of the composite. Differences in HA exposure were observed on the different composite surfaces that affected the morphology of attached cells. In the first 4 h of cell culture, the cells were spread to a higher degree on exposed HA regions of the composites and on PLA than they were on PCL. After 24 h the cells were spread equally on all the samples. The cell activity after 24 h was significantly higher on the polymer/HA composites than on the polymer films. There was no significant difference in the activity of the cells on the various composite materials. However, cells on PCL showed higher activity compared to those on PLA. A polymer surface exhibiting "point exposure" of HA appeared to provide a novel and favorable substrate for primary cell attachment. The cell morphology and activity results indicate a favorable cell/material interaction and suggest that PLA and PCL and their composites with HA may be candidate materials for the reconstruction of bony tissue. Further investigations regarding long-term biomaterial/cell interactions and the effects of acidic degradation products from the biodegradable polymers are required to confirm their utility.
S-Nitrosylation of Matrix Metalloproteinases: Signaling Pathway to Neuronal Cell Death (2002)

Matrix metalloproteinases (MMPs) are implicated in the pathogenesis of neurodegenerative diseases and stroke. However, the mechanism of MMP activation remains unclear. We report that MMP activation involves S-nitrosylation. During cerebral ischemia in vivo, MMP-9 colocalized with neuronal nitric oxide synthase. S-Nitrosylation activated MMP-9 in vitro and induced neuronal apoptosis. Mass spectrometry identified the active derivative of MMP-9, both in vitro and in vivo, as a stable sulfinic or sulfonic acid, whose formation was triggered by S-nitrosylation. These findings suggest a potential extracellular proteolysis pathway to neuronal cell death in which S-nitrosylation activates MMPs, and further oxidation results in a stable posttranslational modification with pathological activity.
Expression of human apolipoprotein B90 in transgenic mice. Demonstration that apolipoprotein B90 lacks the structural requirements to form lipoprotein. (1994)

Lipoprotein(a) (Lp(a)) is a lipoprotein formed by the disulfide linkage of apolipoprotein(a) (apo(a)) to the apoB100 of a low density lipoprotein particle. Earlier site-directed mutagenesis studies of apo(a) demonstrated that apo(a) cysteine 4057 is required for the disulfide linkage; however, the cysteine residue within apoB100 that is involved in the disulfide bond has not been identified. We previously demonstrated that the apoB100 produced by human apoB transgenic mice binds to apo(a) and forms Lp(a) (Linton, M.F., Farese, R. V., Jr., Chiesa, G., Grass, D. S., Chin, P., Hammer, R. E., Hobbs, H.H., and Young, S.G. (1993) J. Clin. Invest. 92, 3029-3037). To further explore the structural features of human apoB that are required for the formation of Lp(a), we used a transposon-interrupted human apoB gene clone to develop transgenic mice that express high levels of a truncated form of human apoB, apoB90, which contains the amino-terminal 4084 amino acids of apoB. In vitro incubation of apo(a) with the plasma of human apoB90 transgenic mice did not yield Lp(a), as judged by Western blots of SDS-polyacrylamide gels or by a monoclonal antibody-based radioimmunoassay. In contrast, incubation of apo(a) with the plasma of a mouse that expressed an equivalent amount of the full-length apoB100 did yield Lp(a). In addition to these in vitro incubation studies, no Lp(a) could be detected in the plasma of a "double transgenic" mouse expressing both human apoB90 and apo(a). These data indicate that the carboxyl-terminal 10% of apoB100 contains amino acid sequences that are essential for the formation of Lp(a).