gebhart/patrepeval huggingface dataset:
Disruption of the ICOS-B7RP-1 Costimulatory Pathway Leads to Enhanced Hepatic Immunopathology and Increased Gamma Interferon Production by CD4 T Cells in Murine Schistosomiasis (2003)

Morbidity and mortality in schistosomiasis are largely due to an immune response mediated by CD4 T lymphocytes. Since lymphocyte activation is shaped by costimulatory signals, the specific functions of different costimulatory pathways are of increasing interest. We now examined the role of the inducible costimulatory molecule (ICOS) and its ligand B7-related protein 1 (B7RP-1) in the experimental murine schistosome infection by blocking this costimulatory pathway with monoclonal antibody against ICOS, administered daily by intraperitoneal injection during the patent phase of the disease. The treated mice exhibited enhanced hepatic immunopathology characterized by enlarged egg granulomas and pronounced parenchymal inflammation with hepatocellular necrosis, resulting in elevated liver enzyme levels in serum. Most strikingly, there was a sharp increase in gamma interferon (IFN-gamma) production by schistosome egg antigen-stimulated granuloma cells, bulk mesenteric lymph node (MLN) cells, and purified MLN CD4 T cells, which contrasted with a more discreet change in the Th2-type cytokines interleukin 4 (IL-4) and IL-10. These findings suggest that the ICOS-B7RP-1 costimulatory pathway serves primarily to control IFN-gamma production, thereby promoting a cytokine environment conducive to limited hepatic damage.
Human Monoclonal Antibody to Hepatitis C Virus E1 Glycoprotein That Blocks Virus Attachment and Viral Infectivity (2004)

Human antibodies elicited in response to hepatitis C virus (HCV) infection are anticipated to react with the native conformation of the viral envelope structure. Isolation of these antibodies as human monoclonal antibodies that block virus binding and entry will be useful in providing potential therapeutic reagents and for vaccine development. H-111, an antibody to HCV envelope 1 protein (E1) that maps to the YEVRNVSGVYH sequence and is located near the N terminus of E1 and is able to immunoprecipitate E1E2 heterodimers, is described. Binding of H-111 to HCV E1 genotypes 1a, 1b, 2b, and 3a indicates that the H-111 epitope is highly conserved. Sequence analysis of antibody V regions showed evidence of somatic and affinity maturation of H-111. Finally, H-111 blocks HCV-like particle binding to and HCV virion infection of target cells, suggesting the involvement of this epitope in virus binding and entry.
Isolation of a Novel Platelet-Derived Growth Factor-Responsive Precursor from the Embryonic Ventral Forebrain (2004)

Oligodendrocyte progenitor cells express platelet-derived growth factor (PDGF) receptor-alpha and, when expanded in PDGF only, have been shown to generate oligodendrocytes and astrocytes but never neurons. Recent evidence suggests that oligodendrocytes are generated by a common progenitor that also generates neurons but not astrocytes. We used the neurosphere culture system to isolate embryonic ventral forebrain, PDGF-responsive precursors (PRPs). We report that the medial ganglionic eminence is the source of PRP-generated neurospheres and that the progeny can differentiate into parvalbumin-positive interneurons, oligodendrocytes, and astrocytes. Thyroid hormone and bone morphogenetic protein-2 (BMP-2) promote the mutually exclusive differentiation of oligodendrocytes and neurons, respectively, whereas ciliary neurotrophic factor acts with BMP-2 to suppress OLIG2 expression and promote astroglial differentiation. PRPs require fibroblast growth factor-2 together with PDGF to maintain self-renewal, which is dependent on sonic hedgehog signaling. We present evidence for forebrain oligodendrocytes and parvalbumin-positive interneurons being generated by a common precursor and elucidate signals regulating the multiple differentiation routes of the progeny of this precursor.
Evaluation of Collagen Crosslinking Techniques (1983)

The properties of collagen films crosslinked by physical and chemical techniques were compared to the properties of films crosslinked with glutaraldehyde (GTA). Physical techniques studied include exposure to short wave (254 nm) u.v. irradiation and severe dehydration. Chemical techniques studied include immersion of collagen films in aqueous solutions of cyanamide or GTA. Collagen films exposed to combinations of aqueous solutions of cyanamide and severe dehydration had moduli of elasticity, swelling ratios and resistance to bacterial collagenase similar to films crosslinked with GTA. Theoretical calculations based on amino acid composition indicate that approximately seven times as many amino acid residues are capable of forming crosslinks using cyanamide or severe dehydration procedures as compared to GTA crosslinking. In addition, using severe dehydration or cyanamide forms crosslinks involving both amino and carboxyl residues which may allow these procedures to act synergistically. Based on our studies this two-step procedure effectively crosslinks collagen-based biomaterials while the only by-product of this reaction is water-soluble urea. Preliminary biocompatibility studies suggest that this crosslinking procedure may allow for pronounced tissue ingrowth.
Use of Capillary Electrophoresis (CE) to Determine Metabolic Organic Acids in Milk (2001)

Abstract of paper presented at the 54th Annual Reciprocal Meat Conference (2001).
The human placenta methylome (2013)

Tissue-specific DNA methylation is found at promoters, enhancers, and CpG islands but also over larger genomic regions. In most human tissues, the vast majority of the genome is highly methylated (>70%). Recently, sequencing of bisulfite-treated DNA (MethylC-seq) has revealed large partially methylated domains (PMDs) in some human cell lines. PMDs cover up to 40% of the genome and are associated with gene repression and inactive chromatin marks. However, to date, only cultured cells and cancers have shown evidence for PMDs. Here, we performed MethylC-seq in full-term human placenta and demonstrate it is the first known normal tissue showing clear evidence of PMDs. We found that PMDs cover 37% of the placental genome, are stable throughout gestation and between individuals, and can be observed with lower sensitivity in Illumina 450K Infinium data. RNA-seq analysis confirmed that genes in PMDs are repressed in placenta. Using a hidden Markov model to map placental PMDs genome-wide and compare them to PMDs in other cell lines, we found that genes within placental PMDs have tissue-specific functions. For regulatory regions, methylation levels in promoter CpG islands are actually higher for genes within placental PMDs, despite the lower overall methylation of surrounding regions. Similar to PMDs, polycomb-regulated regions are hypomethylated but smaller and distinct from PMDs, with some being hypermethylated in placenta compared with other tissues. These results suggest that PMDs are a developmentally dynamic feature of the methylome that are relevant for understanding both normal development and cancer and may be of use as epigenetic biomarkers.
The lateral instability problem in electrostatic comb drive actuators: modeling and feedback control (2006)

Comb drives inherently suffer from electromechanical instability called lateral pull-in, side pull-in or, sometimes, lateral instability. Although fabricated to be perfectly symmetrical, the actuator's comb structure is always unbalanced, causing adjacent finger electrodes to contact each other when voltage–deflection conditions are favorable. Lateral instability decreases the active traveling range of the actuator, and the problem is typically approached by improving the mechanical design of the suspension. In this paper, a novel approach to counteracting the pull-in phenomenon is proposed. It is shown that the pull-in problem can be successfully counteracted by introducing active feedback steering of the lateral motion. In order to do this, however, the actuator must be controllable in the lateral direction, and lateral deflection measurements need to be available. It is shown herein how to accomplish this. The experimentally verified dynamic model of the comb drive is extended with a lateral motion model. The lateral part of the model is verified through experimental results and finite element analysis and is hypothetically extended to accommodate both sensor and actuator functionalities for lateral movement. A set of simulations is performed to illustrate the improved traveling range gained by the controller.
Mammary fibroadenoma and some phyllodes tumour stroma are composed of CD34+ fibroblasts and factor XIIIa+ dendrophages (1996)

Fibroadenomas and mammary phyllodes tumour arise by proliferation of mammary stroma and epithelial elements. However, it is the stromal element that determines the biology of these biphasic tumours. Normal mammary stroma, like most collagenous connective tissue, contains resident populations of CD34+ dendritic interstitial cells and scattered factor XIIIa+ collagen-associated dendrophages. Actin+myofibroblasts are usually absent from mammary stroma in non-disease states. To determine whether CD34+ and factor XIIIa+ cells proliferate in fibroadenomas and phyllodes tumours, and to study myofibroblastic differentiation in these lesions, we examined 19 fibroadenomas in 14 patients along with five low grade and two high grade phyllodes tumours. We employed antibodies against the human progenitor cell antigen CD34, coagulation factor XIIIa and HHF-35 actin. In three fibroadenomas and two phyllodes tumours, we used Ki-67 antigen to study cell proliferation and oestrogen and progesterone receptors to study possible hormonal influence on stromal cells. In all fibroadenomas, CD34 strongly stained interlobular, pericanalicular and intracanalicular fibroblasts with collagenous and/or myxoid features. Four low grade phyllodes tumours also had CD34+ fibroblasts as did one high grade tumour. Actin reactivity varied and was most pronounced in six fibroadenomas resembling the so-called cellular variant, while seven regular fibroadenomas had no actin+stromal cells and six had only focal and weak actin+stromal cells. Factor XIIIa+ cells were prominently admixed in the stroma of all tumours studied comprising from 5% to 20% in fibroadenomas and, focally, up to 50% in phyllodes tumours. Oestrogen and progesterone receptors were expressed only in glandular elements. Ki-67 index in stromal cells was 1% to 3% in fibroadenoma, 10% to 20% in low grade, and 20% to 40% in high grade phyllodes tumour. We conclude that fibroadenomas and some phyllodes tumours are composed of CD34+ fibroblasts that show varying myxoid, collagenous or myofibroblastic differentiation. The fibroblasts are accompanied by a subset of dendritic histiocytes that express factor XIIIa. Fibroadenoma variants show prominent collagenous actin+myofibroblastic differentiation of CD34+ stromal cells, sometimes with a gradient of CD34 down-regulation. Fine-needle or limited stereotactic core biopsy of these biphasic tumours, if they yield only stromal cells, must be distinguished from other CD34+ stromal tumours. Increased factor XIIIa+ dendrophage populations were seen in phyllodes tumours, especially in two high grade tumours that had malignant fibrous histiocytoma-like features, suggesting clonal evolution toward the fibrohistiocytic final pathway. Further study of CD34 and factor XIIIa+ mammary stromal cells in larger numbers of phyllodes tumours might ascertain whether increasing factor XIIIa reactivity correlates with differentiation and increased tumour aggressiveness.
Endogenous Androgens and Carotid Intimal-Medial Thickness in Women (1999)

The influence of endogenous androgens on atherosclerotic disease in women is unknown. In this study involving 101 pre- and post-menopausal females, we evaluated the relationship between serum androgen levels and both carotid artery intimal-medial thickness (IMT) and major cardiovascular risk factors. In addition to evaluation of blood pressure, body mass index, and waist-to-hip ratio, serum dehydroepiandrosterone sulfate (DHEA-S), androstenedione (A), total testosterone (TTS), free testosterone (FTS), insulin, cholesterol (total and high density lipoproteins), triglycerides, and glucose were measured. All women underwent carotid ultrasonography. Spearman correlation coefficients showed that serum DHEA-S and A levels were negatively related (P < 0.03-0.0004) to several IMT measures. Higher tertiles of DHEA-S, A, and FTS corresponded to significantly lower measures of carotid thickness. DHEA-S, and all androgens were inversely related to age (P < 0.03 or less), showing no unfavorable association with major cardiovascular risk factors. In contrast, serum DHEA-S was negatively associated with WHR (P < 0.02), while A was negatively associated with body mass index (P < 0.02). Stepwise multiple regression analysis indicated that A and FTS showed an inverse association with IMT measures (P < 0.05-0.001). In conclusion, our data indicate that in women serum DHEA-S and androgens decline with age and that normal hormonal levels are not associated with major cardiovascular risk factors. They also show that higher DHEA-S and androgen concentrations are related to lower carotid wall thickness; for A this association is independent of cardiovascular risk factors. Our results suggest that, in the physiological range, DHEA-S and androgens in women are correlated with lower risk of carotid artery atherosclerosis.
AR splice variant 7 (AR-V7) and response to taxanes in men with metastatic castration-resistant prostate cancer (mCRPC). (2015)

138 Background: AR-V7 is a truncated form of AR that lacks the ligand-binding domain but remains constitutively active. We previously showed that detection of AR-V7 from circulating tumor cells (CTCs) in men with mCRPC was associated with primary resistance to enzalutamide and abiraterone. Here, we hypothesized that AR-V7[+] patients would retain sensitivity to taxane chemotherapy. Methods: We used a qRT-PCR assay to interrogate CTCs for AR-V7 mRNA in prospectively enrolled patients with mCRPC starting docetaxel or cabazitaxel. We sought associations between AR-V7 status and PSA response rates (the primary endpoint), PSA progression-free survival (PSA-PFS), and clinical/radiographic progression-free survival (PFS). Multivariable regressions were performed to determine the independent effect of AR-V7 status on clinical outcomes. 36 taxane-treated men were required to produce a 2-sided 95% CI for the difference in PSA response rates (between AR-V7[+] and AR-V7[–] men) with an upper bound of 60%, assuming that 30% of men would be AR-V7[+]. Results: 37 taxane-treated patients were enrolled, and 17 (45.9%) had detectable AR-V7 in CTCs. PSA responses were achieved in both AR-V7[+] and AR-V7[–] men (41% vs 65%, P=0.19). Median PSA-PFS was comparable in AR-V7[+] and AR-V7[–] men (4.5 vs 6.2 mo, HR 1.72, P=0.32). Likewise, median PFS was comparable in AR-V7[+] and AR-V7[–] men (5.1 vs 6.9 mo, HR 2.65, P=0.11). After incorporating data from our prior study in 62 abi/enza-treated patients, it was observed that clinical outcomes in AR-V7[+] men were superior with taxanes than with abi/enza, while outcomes did not differ by treatment type in AR-V7[–] men. For example, in AR-V7[+] men, PSA responses were higher in taxane-treated versus abi/enza-treated men (41% vs 0%, P&lt;0.001), and median PSA-PFS and PFS were longer in taxane-treated men (HR for PSA-PFS = 0.19, P=0.001; HR for PFS = 0.21, P=0.003). Conclusions: Detection of AR-V7 in CTCs from men with mCRPC is not associated with primary resistance to taxane chemotherapy, and such patients may retain sensitivity to taxanes. Further, in AR-V7[+] men, taxanes appear to be more efficacious than abi/enza. AR-V7 may represent a treatment-selection marker in mCRPC.
Direct Reductive Alkylation of Amino Acids: Synthesis of Bifunctional Chelates for Nuclear Imaging (2004)

A family of effective bifunctional chelators for technetium- and rhenium-based radiopharmaceuticals was conveniently synthesized in high yields through direct reductive N-alkylations of amino acids and their analogues with aldehydes, using NaBH(OAc)3 as an efficient reagent. The mono-, di-, tetra- and even mixed alkylated amino acid derivatives were all prepared in one-pot synthesis.
Curcumin as a Potential Treatment for COVID-19 (2021)

Coronavirus disease 2019 (COVID-19) is an infectious disease that rapidly spread throughout the world leading to high mortality rates. Despite the knowledge of previous diseases caused by viruses of the same family, such as MERS and SARS-CoV, management and treatment of patients with COVID-19 is a challenge. One of the best strategies around the world to help combat the COVID-19 has been directed to drug repositioning; however, these drugs are not specific to this new virus. Additionally, the pathophysiology of COVID-19 is highly heterogeneous, and the way of SARS-CoV-2 modulates the different systems in the host remains unidentified, despite recent discoveries. This complex and multifactorial response requires a comprehensive therapeutic approach, enabling the integration and refinement of therapeutic responses of a given single compound that has several action potentials. In this context, natural compounds, such as Curcumin, have shown beneficial effects on the progression of inflammatory diseases due to its numerous action mechanisms: antiviral, anti-inflammatory, anticoagulant, antiplatelet, and cytoprotective. These and many other effects of curcumin make it a promising target in the adjuvant treatment of COVID-19. Hence, the purpose of this review is to specifically point out how curcumin could interfere at different times/points during the infection caused by SARS-CoV-2, providing a substantial contribution of curcumin as a new adjuvant therapy for the treatment of COVID-19.
Influence of Adipose Tissue Distribution on the Biological Activity of Androgensa (1990)

To establish whether the conversion of androstenedione (A) to estrogens and 5 alpha-reduced metabolites in human adipose tissue was determined by the site of origin of the tissue, studies were carried out on adipose stromal cells from different body sites. Adipose tissue was obtained from the breast, omentum, abdomen, lower thigh, upper thigh, buttock, and flank from patients undergoing liposuction for cosmetic reasons or at surgery. Stromal cells were isolated after incubation of the adipose tissue with collagenase and were grown in culture using alpha-minimal essential medium (MEM) + 15% fetal calf serum. Studies of A metabolism were carried out when the cells were between days 4 and 12 in culture. After an 8-hour incubation with (3H)-A as substrate, estrone (E1), testosterone (T), 5 alpha-androstanedione (5 alpha-A-dione), androsterone (AND), and dihydrotestosterone (DHT) were isolated using thin layer and paper chromatography. The conversion per 1 x 10(6) cells of A of E1 was more than 10-fold greater in the upper thigh, buttock, and flank than in the breast, lower thigh, abdomen, or omentum (0.13-3.0 vs 0.01-0.09%). The formation of 5 alpha-reduced androgens varied from 0.86-10% and was similar in tissue from different body sites. Cortisol (10(-7) M) stimulated E1 formation 3- to 10-fold in cells from all sites, whereas 5 alpha-reductase activity was either unchanged or increased moderately (up to twofold). In cells from the abdomen, omentum, and lower thigh, the formation of 5 alpha-reduced androgens was more than 10-fold greater than the formation of E1. In cells from the upper thigh, buttock, and flank, E1 formation was comparable to 5 alpha-reduced androgen formation. These studies show marked differences in the relative conversion of A to estrogens and 5 alpha-reduced androgens in adipose stromal cells depending on their site of origin, and they suggest that the distribution of body fat may be a major factor in determining the biologic effects of secreted androgens.
Human Vascular Endothelial Cells Catabolise Exogenous Glycosaminoglycans by a Novel Route (1992)

Heparin and other anticoagulant glycosaminoglycans were radiolabelled with 125I and their catabolism by human vascular endothelial cells in culture was studied. Heparin, heparan sulphate and pentosan polysulphate were associated with the cellular fraction and incorporated into the subendothelial matrix, but dermatan sulphate was not found in either fraction. High molecular weight, fully desulphated carbohydrate chains were major catabolic products of all those glycosaminoglycans which were taken up by the cells. Pentosan polysulphate was not degraded further, but the catabolism of heparan sulphate, and to a lesser extent that of heparin, also yielded small oligosaccharides. Thus the first step in catabolism of exogenous glycosaminoglycans by human vascular endothelial cells appears to be complete desulphation, which destroys their biological activity, followed by depolymerisation of the carbohydrate chain. This alternative to the sequential action of lysosomal exoenzymes is dependent upon binding to the cell; thus dermatan sulphate, which is not associated with the cellular fraction, is not catabolised.
Site‐directed mutagenesis of two conserved charged amino acids in the N‐terminal region of α subunit of E. coli‐F0F1 (1996)

Two conserved charged amino acids of the N-terminal 'crown' region of the alpha subunit of E. coli-F(1), alpha-D36 and alpha-R40 were exchanged for chemically related (alpha-D36-->E, alpha-R40-->K) or unrelated amino acids (alpha D-36-->K, alpha R40-->G), respectively, by employing oligonucleotide-directed mutagenesis. ATP formation and ATP hydrolyzing activity of isolated plasma membrane vesicles was strongly inhibited in mutant HS2 (alpha-D36-->K), but only slightly affected in the other mutants. The inhibition is not due to a lower content of F0F1 in HS2. In this mutant the extent of the proton gradient generated by ATP hydrolysis was more than 80% inhibited; in all other transformants much smaller effects were observed. The proton gradient established by NADH oxidation was 33% decreased in HS2, but was decreased to a lesser extent in all other mutants. After blockage of F0 by DCCD treatment, the same NADH-induced proton gradient was obtained in all transformants including HS2. This and the fact that the activity of NADH oxidation was unchanged indicate increased proton leakiness of F0F1 carrying the alpha-D36-->K mutation. In F1 alpha-D36 is located in a domain contacting the beta subunit in the vicinity of the arginine beta-R52. The effect of alpha-D36-->K replacement on catalysis and coupling thus may be due to an electrostatic repulsive effect in the crown region which alters the alpha and beta interaction.