gebhart/patrepeval huggingface dataset:
Lovastatin Has Significant Activity against Zygomycetes and Interacts Synergistically with Voriconazole (2005)

Zygomycetes are emerging opportunistic molds resistant to most conventional antifungals. We evaluated the in vitro activity of lovastatin (LOV), a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, against seven clinical isolates of Zygomycetes by using standard microdilution methods in three different media, disk diffusion testing, and viability dye staining. To further study the in vivo efficacy of LOV against zygomycetes, we developed a Drosophila melanogaster model of zygomycosis. In different experiments, groups of Toll-deficient (Tl) flies fed LOV-containing food were subsequently injected with two representative Zygomycetes isolates (Mucor and Rhizopus spp.). Finally, we examined the effects of LOV on voriconazole (VRC) activity against zygomycetes in vitro by checkerboard dilution, Epsilometer test-based methods, and bis-(1,3-dibutylbarbituric acid) trimethine oxonol staining and in vivo in Tl flies fed food containing LOV plus VRC and infected with zygomycetes. LOV exhibited significant, medium, and strain-independent fungicidal activity against all Zygomycetes isolates in vitro by all testing methods (MIC50, 48.0 microg/ml; 50% minimal fungicidal concentration, 56.0 microg/ml; 50% effective concentration, 29.4 microg/ml [6.6 to 38.9 microg/ml]). Tl flies fed LOV-containing food and infected with Mucor had a significantly better 6-day survival rate than did infected Tl flies fed regular food (P = 0.0005). LOV displayed in vitro synergy with VRC against all Zygomycetes isolates (fractional inhibitory concentration index, 0.104 to 0.290) by all methods used. LOV also displayed synergy with VRC in the Drosophila model of zygomycosis (P < 0.01). LOV is significantly active against zygomycetes and synergizes with triazoles inherently resistant to them, such as VRC. The clinical significance of these findings needs to be further explored.
Automatic extraction of clickable structured web contents for name entity queries (2010)

Today the major web search engines answer queries by showing ten result snippets, which need to be inspected by users for identifying relevant results. In this paper we investigate how to extract structured information from the web, in order to directly answer queries by showing the contents being searched for. We treat users' search trails (i.e., post-search browsing behaviors) as implicit labels on the relevance between web contents and user queries. Based on such labels we use information extraction approach to build wrappers and extract structured information. An important observation is that many web sites contain pages for name entities of certain categories (e.g., AOL Music contains a page for each musician), and these pages have the same format. This makes it possible to build wrappers from a small amount of implicit labels, and use them to extract structured information from many web pages for different name entities. We propose STRUCLICK, a fully automated system for extracting structured information for queries containing name entities of certain categories. It can identify important web sites from web search logs, build wrappers from users' search trails, filter out bad wrappers built from random user clicks, and combine structured information from different web sites for each query. Comparing with existing approaches on information extraction, STRUCLICK can assign semantics to extracted data without any human labeling or supervision. We perform comprehensive experiments, which show STRUCLICK achieves high accuracy and good scalability.
Effect of Pravastatin on Outcomes after Cardiac Transplantation (1995)

After cardiac transplantation, pravastatin had beneficial effects on cholesterol levels, the incidence of rejection causing hemodynamic compromise, one-year survival, and the incidence of coronary vasculopathy.
Interprocess Communication in Charlotte (1987)

The unique system provides powerful interprocess communication that uses duplex links, does not buffer messages in the kernel, and does not block on communication requests.
Amino-terminal processing of proteins: hemoglobin South Florida, a variant with retention of initiator methionine and N alpha-acetylation. (1985)

The hemoglobin variant South Florida has been shown by protein sequencing and fast-atom-bombardment mass spectroscopy to have a substitution of methionine for the NH2-terminal valine of the beta-globin chain. In addition, there was complete retention of the initiator methionine on the mutant polypeptide. Approximately 20% of the protein was acetylated at the NH2 terminus of the beta chain. A search of a comprehensive data bank of protein and gene sequences revealed 84 unrelated vertebrate proteins that have not undergone cleavage of leader sequences. A highly nonrandom distribution of residues at the NH2 termini of these proteins predicts removal of the initiator methionine as well as NH2-terminal acetylation. Proteins that undergo removal commonly have serine, alanine, glycine, or valine, as the NH2-terminal residues. The first three residues favor N alpha-acetylation. Proteins that retain the initiator methionine commonly have a charged residue or methionine at the second position. Information on Hb South Florida and other hemoglobins coupled with this survey of primary sequence provides insights into the NH2-terminal processing of proteins.
GP41-Specific Antibody Blocks Cell-Free HIV Type 1 Transcytosis through Human Rectal Mucosa and Model Colonic Epithelium (2010)

Monostratified epithelial cells translocate HIV type 1 (HIV-1) from the apical to the basolateral surface via vesicular transcytosis. Because acutely transmitted HIV-1 is almost exclusively CCR5-tropic and human intestinal epithelial cells preferentially transcytose CCR5-tropic virus, we established epithelial monolayers using polarized HT-29 cells transduced to express CCR5, and an explant system using normal human rectal mucosa, to characterize biological parameters of epithelial cell transcytosis of HIV-1 and assess antiviral Ab blockade of transcytosis. The amount of cell-free HIV-1 transcytosed through the epithelial monolayer increased linearly in relation to the amount of virus applied to the apical surface, indicating transcytosis efficiency was constant (r(2) = 0.9846; p < 0.0001). The efficiency of HIV-1 transcytosis ranged between 0.05 and 1.21%, depending on the virus strain, producer cell type and gp120 V1-V3 loop signature. Inoculation of HIV-1 neutralizing Abs to the immunodominant region (7B2) or the conserved membrane proximal external region (2F5) of gp41 or to cardiolipin (IS4) onto the apical surface of epithelial monolayers prior to inoculation of virus significantly reduced HIV-1 transcytosis. 2F5 was the most potent of these IgG1 Abs. Dimeric IgA and monomeric IgA, but not polymeric IgM, 2F5 Abs also blocked HIV-1 transcytosis across the epithelium and, importantly, across explanted normal human rectal mucosa, with monomeric IgA substantially more potent than dimeric IgA in effecting transcytosis blockade. These findings underscore the potential role of transcytosis blockade in the prevention of HIV-1 transmission across columnar epithelium such as that of the rectum.
Tregitope update: Mechanism of action parallels IVIg (2012)

In the course of screening immunoglobulin G (IgG) sequences for T cell epitopes, we identified novel Treg epitope peptides, now called Tregitopes, contained in the highly conserved framework regions of Fab and Fc. Tregitopes may provide one explanation for the expansion and stimulation of Treg cells following intravenous immunoglobulin (IVIg) therapy. Their distinguishing characteristics include in silico signatures that suggest high-affinity binding to multiple human HLA class II DR and conservation across IgG isotypes and mammalian species with only minor amino acid modifications. Tregitopes induce expansion of CD4(+)/CD25(hi)/FoxP3(+) T cells and suppress immune responses to co-incubated antigens in vitro. By comparing the human IgG Tregitopes (hTregitopes 167 and 289, located in the IgG CH1 and CH2 domains) and Fab to murine sequences, we identified class II-restricted murine Tregitope homologs (mTregitopes). In vivo, mTregitopes suppress inflammation and reproducibly induce Tregs to expand. In vitro studies suggest that the Tregitope mechanism of action is to induce Tregs to respond, leading to production of regulatory signals, followed by modulation of dendritic cell phenotype. The identification of Treg epitopes in IgG suggests that additional Tregitopes may also be present in other autologous proteins; methods for identifying and validating such peptides are described here. The discovery of Tregitopes in IgG and other autologous proteins may lead to the development of new insights as to the role of Tregs in autoimmune diseases.
Enhanced early chondrogenesis in articular defects following arthroscopic mesenchymal stem cell implantation in an equine model (2007)

Mesenchymal stem cells (MSCs) provide an important source of pluripotent cells for musculoskeletal tissue repair. This study examined the impact of MSC implantation on cartilage healing characteristics in a large animal model. Twelve full-thickness 15-mm cartilage lesions in the femoropatellar articulations of six young mature horses were repaired by injection of a self-polymerizing autogenous fibrin vehicle containing mesenchymal stem cells, or autogenous fibrin alone in control joints. Arthroscopic second look and defect biopsy was obtained at 30 days, and all animals were euthanized 8 months after repair. Cartilage repair tissue and surrounding cartilage were assessed by histology, histochemistry, collagen type I and type II immunohistochemistry, collagen type II in situ hybridization, and matrix biochemical assays. Arthroscopic scores for MSC-implanted defects were significantly improved at the 30-day arthroscopic assessment. Biopsy showed MSC-implanted defects contained increased fibrous tissue with several defects containing predominantly type II collagen. Long-term assessment revealed repair tissue filled grafted and control lesions at 8 months, with no significant difference between stem cell-treated and control defects. Collagen type II and proteoglycan content in MSC-implanted and control defects were similar. Mesenchymal stem cell grafts improved the early healing response, but did not significantly enhance the long-term histologic appearance or biochemical composition of full-thickness cartilage lesions.
A New Class of Macrocyclic Lanthanide Complexes for Cell Labeling and Magnetic Resonance Imaging Applications (2005)

Lanthanide complexes have wide applications in biochemical research and biomedical imaging. We have designed and synthesized a new class of macrocyclic lanthanide chelates, Ln/DTPA-PDA-C(n), for cell labeling and magnetic resonance imaging (MRI) applications. Two lipophilic Gd3+ complexes, Gd/DTPA-PDA-C(n) (n = 10, 12), labeled a number of cultured mammalian cells noninvasively at concentrations as low as a few micromolar. Cells took up these agents rapidly and showed robust intensity increases in T1-weighed MR images. Labeled cells showed normal morphology and doubling time as control cells. In addition to cultured cells, these agents also labeled primary cells in tissues such as dissected pancreatic islets. To study the mechanism of cellular uptake, we applied the technique of diffusion enhanced fluorescence resonance energy transfer (DEFRET) to determine the cellular localization of these lipophilic lanthanide complexes. After loading cells with a luminescent complex, Tb/DTPA-PDA-C10, we observed DEFRET between the Tb3+ complex and extracellular, but not intracellular, calcein. We concluded that these cyclic lanthanide complexes label cells by inserting two hydrophobic alkyl chains into cell membranes with the hydrophilic metal binding site facing the extracellular medium. As the first imaging application of these macrocyclic lanthanide chelates, we labeled insulin secreting beta-cells with Gd/DTPA-PDA-C12. Labeled cells were encapsulated in hollow fibers and were implanted in a nude mouse. MR imaging of implanted beta-cells showed that these cells could be followed in vivo for up to two weeks. The combined advantages of this new class of macrocyclic contrast agents ensure future imaging applications to track cell movement and localization in different biological systems.
Attempted Experimental Modification of the Postlaminectomy Membrane by Local Instillation of Recombinant Tissue-Plasminogen Activator Gel (1993)

A prospective, randomized, blinded trial involving 25 adult mongrel dogs was performed to evaluate whether placement of a fat graft or local instillation of recombinant tissue-plasminogen activator gel [rt-PA] could modify the development of a postlaminectomy membrane. One component of the study involved the performance of a lumbar laminectomy and placement of gel rt-PA, free fat, or no tissue placement over the exposed dura mater. Three months later the animals were killed and sections of spine were removed en bloc, decalcified, and examined histologically. No significant differences were found in the degree of cellular fibrosis or heavy collagen production. A similar laminectomy at another lumbar level was also followed by gel rt-PA, free fat, or no tissue placement. Three months after surgery, surgery was performed again at this level immediately before death. There were no differences in the adhesiveness of the laminectomy membrane to dura mater or roots It was concluded that the local Instillation of gel rt-PA aftar laminectomy d id not inhibit scar formation or scar adherence to the dura mater.
Bactericidal Activities of Antibiotics against Intracellular Francisella tularensis (2000)

MICs of many antibiotics for Francisella tularensis are low in axenic medium, whereas only aminoglycosides, tetracyclines, and fluoroquinolones are useful in treating tularemic patients. In an in vitro cell system, only these antibiotics, rifampin, and telithromycin were bactericidal against intracellular F. tularensis. These results correlate better with clinical data than MIC data do.
Performance degradation of PRML channels due to nonlinear distortions (1991)

The effects of nonlinear distortions on the performance of a partial response/maximum likelihood detection (PRML) channel are presented. The nonlinear distortions are introduced during the process of writing (transition shift) and reading (head distortion) data from a magnetic medium. Measurements were taken on the bench using simulated waveforms based on the Lorentzian wave shape, digital equalizer, and experimental PRML channel hardware. Head asymmetry and saturation, typical of experimental magnetoresistive heads, were modeled by adding quadratic and cubic distortions, respectively. Noise was injected to the unequalized signal, presenting a colored spectrum to the input of the detector. The errors were detected by comparing the output of the detector and a reference non-return-to-zero (NRZ) pattern. The system signal-to-noise ratio was computed using a sample distribution method. The effect of various kinds of nonlinearities on the eye diagram was studied, and templates which are useful in identifying the type of nonlinearity present in a real system were generated.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
A novel polymorphism in human cytosine DNA-methyltransferase-3B promoter is associated with an increased risk of lung cancer. (2002)

DNA repair is central to genomic integrity. Reduced expression of several nucleotide excision repair genes has been demonstrated to be associated with increased risk of lung cancer. Because methylation of gene promoters is one of the major regulatory mechanisms of gene expression and most nucleotide excision repair gene promoters have not been fully characterized, we hypothesized that genetic variants of the genes that are responsible for regulating genomic methylation are associated with increased risk of lung cancer. Recently, we identified a C-->T transition at a novel promoter region of cytosine DNA-methyltransferase-3B (DNMT3B) and found that this polymorphic transition significantly increases the promoter activity. In this hospital-based case-control study of 319 patients with incident lung cancer and 340 healthy controls frequency matched on age (+/-5 years), sex, ethnicity, and smoking status, we genotyped subjects for this DNMT3B promoter polymorphism to determine the association between this genetic variant and risk of lung cancer. Compared with CC homozygotes, CT heterozygotes had a >2-fold increased risk of lung cancer [adjusted odds ratio (OR), 2.13; 95% confidence interval (CI), 1.47-3.08] and TT homozygotes an OR of 1.42 (95% CI, 0.91-2.21). The combined variant genotype (CT + TT) was associated with a nearly 2-fold increased risk (adjusted OR, 1.88; 95% CI, 1.32-2.66). These results suggest that this novel variant of DNMT3B is associated with increased risk of lung cancer and may contribute to identifying individuals genetically susceptible to tobacco-induced cancers. Additional studies on the underlying molecular mechanism of this polymorphism are warranted.
Is pulmonary vascular disease reversible with PPAR ɣ agonists? (2018)

Abstract Severe angio‐obliterative PAH remains a disease characterized by great morbidity and shortened survival. Unfortunately, the only currently available treatments for angio‐obliterative changes are palliative in the form of pulmonary vasodilators evolving from the phosphodiesterase inhibitor sildenafil to endothelin receptor antagonist: Bosentan; while the only definitive treatment is lung transplantation which remains dependent on the availability of donors and the transplant policies which vary widely from a country to another. PPAR s, especially the γ isoform, are largely expressed in pulmonary artery endothelial cells and smooth muscle cells. They are also found on endothelial progenitor cells. Several previous studies have highlighted the role of PPAR γ agonists in reversal of vascular remodeling especially in coronary, carotid and peripheral vascular disease atherosclerotic plaques. Experimental studies have also revealed that PPAR γ activation affects many different pathways; thus, the effect of PPAR γ is multifaceted, affecting almost every pathobiological pathway involved in the development of PAH simultaneously. We thereby hypothesize that PPAR γ agonists may play a key role in reversing severe pulmonary angio‐obliterative changes and promote microvascular regeneration which may substitute the need for heart‐lung transplantation in such patients.
NLRX1 suppresses tumorigenesis and attenuates histiocytic sarcoma through the negative regulation of NF-λB signaling (2016)

Histiocytic sarcoma is an uncommon malignancy in both humans and veterinary species. Research exploring the pathogenesis of this disease is scarce; thus, diagnostic and therapeutic options for patients are limited. Recent publications have suggested a role for the NLR, NLRX1, in acting as a tumor suppressor. Based on these prior findings, we hypothesized that NLRX1 would function to inhibit tumorigenesis and thus the development of histiocytic sarcoma. To test this, we utilized Nlrx1-/- mice and a model of urethane-induced tumorigenesis. Nlrx1-/- mice exposed to urethane developed splenic histiocytic sarcoma that was associated with significant up-regulation of the NF-κB signaling pathway. Additionally, development of these tumors was also significantly associated with the increased regulation of genes associated with AKT signaling, cell death and autophagy. Together, these data show that NLRX1 suppresses tumorigenesis and reveals new genetic pathways involved in the pathobiology of histiocytic sarcoma.
NeuroD1/β2 Contributes to Cell-Specific Transcription of the Proopiomelanocortin Gene (1997)

NeuroD1/beta2 is a basic helix-loop-helix (bHLH) factor expressed in the endocrine cells of the pancreas and in a subset of neurons as they undergo terminal differentiation. We now show that NeuroD1 is expressed in corticotroph cells of the pituitary gland and that it is involved in cell-specific transcription of the proopiomelanocortin (POMC) gene. It was previously shown that corticotroph-specific POMC transcription depends in part on the action of cell-restricted bHLH factors that were characterized as the CUTE (corticotroph upstream transcription element) (M. Therrien and J. Drouin, Mol. Cell. Biol. 13:2342-2353, 1993) complexes. We now demonstrate that these complexes contain NeuroD1 in association with various ubiquitous bHLH dimerization partners. The NeuroD1-containing heterodimers specifically recognize and activate transcription from the POMC promoter E box that confers transcriptional specificity. Interestingly, the NeuroD1 heterodimers activate transcription in synergy with Ptx1, a Bicoid-related homeodomain protein, which also contributes to corticotroph specificity of POMC transcription. In the adult pituitary gland, NeuroD1 transcripts are detected in POMC-expressing corticotroph cells. Taken together with the restricted pattern of Ptx1 expression, these results suggest that these two factors establish the basis of a combinatorial code for the program of corticotroph-specific gene expression.
Synthesis and Characterization of Highly Luminescent Asymmetric Poly(p-phenylene vinylene) Derivatives for Light-Emitting Diodes (2002)

Asymmetric and color tunable poly(p-phenylene vinylene) (PPV) derivatives with a dimethyldodecylsilylphenyl pendant group, poly[2-(3‘-dimethyldodecylsilylphenyl)-1,4-phenylene vinylene] (m-SiPhPPV) and poly[2-(3‘-dimethyldodecylsilylphenyl)-1,4-phenylene vinylene-co-2-methoxy-5-(2‘-ethylhexyl oxy)-1,4-phenylene vinylene] (m-SiPhPPV-co-MEH−PPV), have been synthesized by a dehydrohalogenation method. Newly synthesized, these homo- and copolymers are highly soluble in common organic solvents. The defect-free uniformly thin films easily formed onto the indium tin oxide (ITO) coated glass substrate. The resulting polymers had high molecular weights with narrow polydispersities and high thermal stability up to 400 °C. The copolymers showed better optical and electroluminescent (EL) properties than those of the homopolymer. Single-layer light-emitting devices with an ITO/polymer/Al:Li alloy configuration were fabricated by using the resulting polymers. The maximum EL emissions of m-SiPhPPV and m-SiPhPPV-co-MEHPPV with various monomer feed ratios were observed at 528 and 588−595 nm, respectively. The emission color of the resulting polymers changed from green to orange. The EL properties of the m-SiPhPPV-co-MEH−PPV dramatically improved compared to those of m-SiPhPPV and MEH−PPV. The maximum brightness and the external luminance efficiency of the m-SiPhPPV-co-MEH−PPV were up to 19 180 cd/m2 and 2.9 lm/W. The half lifetime of a single-layer device at 1000 cd/m2 is about 120 h.
Association of Lowered Plasma Carotenoids with Protection Against Cecal Coccidiosis by Diets High in n-3 Fatty Acids (1996)

A series of four experiments was run to assess the effectiveness of diets containing high amounts of n-3 fatty acids in reducing the pathological effects of cecal coccidiosis in chickens caused by Eimeria tenella. To determine whether the dietary effects were related to development of oxidative stress, plasma samples were analyzed for tocopherols and carotenoids. Plasma vitamin E (alpha-tocopherol) values were not consistent between experiments. Total plasma carotenoids, however, were significantly decreased by 2.5 to 20% diet supplementation with fish oil in several experiments. These decreases coincided with significant reductions in lesion scores. Under the experimental conditions, total plasma carotenoid concentrations may serve as a sensitive indicator for oxidative stress, which may be a factor in reducing cecal lesions in E. tenella infections.