gebhart/patrepeval huggingface dataset:
Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. (1994)

Aging in humans is accompanied by a progressive decline in the secretion of the adrenal androgens dehydroepiandrosterone (DHEA) and DHEA sulfate (DS), paralleling that of the GH-insulin-like growth factor-I (GH-IGF-I) axis. Although the functional relationship of the decline of the GH-IGF-I system and catabolism is recognized, the biological role of DHEA in human aging remains undefined. To test the hypothesis that the decline in DHEA may contribute to the shift from anabolism to catabolism associated with aging, we studied the effect of a replacement dose of DHEA in 13 men and 17 women, 40-70 yr of age. A randomized placebo-controlled cross-over trial of nightly oral DHEA administration (50 mg) of 6-month duration was conducted. During each treatment period, concentrations of androgens, lipids, apolipoproteins, IGF-I, IGF-binding protein-1 (IGFBP-1), IGFBP-3, insulin sensitivity, percent body fat, libido, and sense of well-being were measured. A subgroup of men (n = 8) and women (n = 5) underwent 24-h sampling at 20-min intervals for GH determinations. DHEA and DS serum levels were restored to those found in young adults within 2 weeks of DHEA replacement and were sustained throughout the 3 months of the study. A 2-fold increase in serum levels of androgens (androstenedione, testosterone, and dihydrotestosterone) was observed in women, with only a small rise in androstenedione in men. There was no change in circulating levels of sex hormone-binding globulin, estrone, or estradiol in either gender. High density lipoprotein levels declined slightly in women, with no other lipid changes noted for either gender. Insulin sensitivity and percent body fat were unaltered. Although mean 24-h GH and IGFBP-3 levels were unchanged, serum IGF-I levels increased significantly, and IGFBP-1 decreased significantly for both genders, suggesting an increased bioavailability of IGF-I to target tissues. This was associated with a remarkable increase in perceived physical and psychological well-being for both men (67%) and women (84%) and no change in libido. In conclusion, restoring DHEA and DS to young adult levels in men and women of advancing age induced an increase in the bioavailability of IGF-I, as reflected by an increase in IGF-I and a decrease in IGFBP-1 levels. These observations together with improvement of physical and psychological well-being in both genders and the absence of side-effects constitute the first demonstration of novel effects of DHEA replacement in age-advanced men and women.
Capacitive sensor for respiratory monitoring (2016)

Dielectric properties of human lung in chest and diaphragm area are changing during respiratory activity. This process can be monitored measuring capacity of sensor which consists of two or more electrodes attached to the body. A simple device with electrodes for capacitive sensing of respiratory was developed and tested. This capacity was connected to Colpitts oscillator LC circuit and causes frequency change. Two different circuits were tested with the same electrode sets.
Vascular permeability factor/endothelial growth factor (VPF/VEGF): accumulation and expression in human synovial fluids and rheumatoid synovial tissue. (1994)

Vascular permeability factor (VPF, also known as vascular endothelial growth factor or VEGF), is a potent microvascular permeability enhancing cytokine and a selective mitogen for endothelial cells. It has been implicated in tumor angiogenesis and ascites fluid accumulation. Since development of the destructive synovial pannus in rheumatoid arthritis (RA) is associated with changes in vascular permeability (synovial fluid accumulation), synovial cell hyperplasia, and angiogenesis, we examined synovial fluids (SFs) and joint tissue for the expression and local accumulation of VPF/VEGF. VPF/VEGF was detected in all of 21 synovial fluids examined and when measured by an immunofluorimetric assay, ranged from 6.9 to 180.5 pM. These levels are biologically significant, since < 1 pM VPF/VEGF can elicit responses from its target cells, endothelial cells. Levels of VPF/VEGF were highest in rheumatoid arthritis fluids (n = 10), with a mean value (+/- SEM) of 59.1 +/- 18.0 pM, vs. 21.4 +/- 2.3 pM for 11 SFs from patients with other forms of arthritis (p = 0.042). In situ hybridization studies that were performed on joint tissues from patients with active RA revealed that synovial lining macrophages strongly expressed VPF/VEGF mRNA, and that microvascular endothelial cells of nearby blood vessels strongly expressed mRNA for the VPF/VEGF receptors, flt-1 and KDR. Immunohistochemistry performed on inflamed rheumatoid synovial tissue revealed that the VPF/VEGF peptide was localized to macrophages within inflamed synovium, as well as to microvascular endothelium, its putative target in the tissue. Together, these findings indicate that VPF/VEGF may have an important role in the pathogenesis of RA.
Disulfide bonds are localized within the short consensus repeat units of complement regulatory proteins: C4b-binding protein (1989)

Several plasma and membrane proteins belong to a superfamily of structurally related proteins that contain internal homology of a variable number (2-30) of repeating units. Each SCR (short consensus repeat) unit is approximately 60 amino acid residues in length, with the positions of 1 Trp, 2 Pro, and 4 Cys residues being conserved. The aim of this study was to provide experimental evidence that each SCR may exist as an independent structural domain maintained by disulfide bonds. The well-characterized C4b-binding protein (C4BP) with eight SCR units in each of its seven identical chains was chosen for this study. Analysis of the disulfide-bonding pattern indicated that intrachain disulfide bonds may be localized within each SCR unit, with the first and third and the second and fourth half-cystines in each unit being linked. This pattern of disulfides may confer to C4BP (and to other structurally related proteins) a conformation which apparently allows the assembly of the SCR units (4-30) in a tandem fashion. Such an arrangement of the polypeptide chain(s) may explain, in part, the elongated shape of these protein molecules. The structural motif of the SCR units of C4BP is discussed in relation to those previously described for the type II domain of fibronectin and the kringle structure present in various proteins of the coagulation system.
Postpolymerization Modification of Hydroxyl-Functionalized Polymers with Isocyanates (2011)

The postpolymerization functionalization of hydroxyl-group terminated polymers (Mn in the range of 1000–6000 g mol–1) such as poly(ethylene glycol) (PEG), poly(N-isopropylacrylamide) (PNIPAM), poly(N,N-dimethylacrylamide) (PDMAM), and poly(tert-butyl acrylate) (PtBA) with a wide range of functional isocyanate derivatives such as azobenzene, viologen, and anthracene has been investigated. It was shown by 1H and 13C NMR, GPC, Fourier transform infrared spectroscopy (FTIR), and electrospray ionization mass spectrometry (ESI-MS) that a high degree of end-group conversion, typically >98%, with little or no formation of side products can be achieved at ambient temperature. PNIPAM, PDMAM, PtBA, and PHEAM polymers have been obtained by reversible addition–fragmentation chain transfer (RAFT) radical polymerization from a hydroxyl-group containing chain transfer agent (CTA). The formation of the carbamate has been shown to be compatible with the trithiocarbonate end-group of the RAFT polymers. Additionally, this approach allows for the direct functionalization of RAFT polymers without the need of additional steps such as deprotection or aminolysis of the CTA. This route was subsequently used for the preparation of a variety of side-chain functional polymers from poly(N-hydroxyethyl acrylamide) (PHEAM). Three different high yielding methods have been employed to prepare the isocyanates (R–NCO). Either amino or carboxylic acid precursors have been converted into the desired R–NCO or hydroxyl group moieties have been reacted with an excess of 1,6-hexamethylene diisocyanate (HDI) to statistically form the monofunctional product.
Emergence of Constitutively Active Estrogen Receptor-α Mutations in Pretreated Advanced Estrogen Receptor–Positive Breast Cancer (2014)

In this study, we show evidence for the temporal selection of functional ESR1 mutations as potential drivers of endocrine resistance during the progression of ER(+) breast cancer.
Hypoxia Inducible Factor 1α Signaling in Fractionated Radiation-Induced Lung Injury: Role of Oxidative Stress and Tissue Hypoxia (2010)

To investigate the relationship of HIF1alpha signaling to oxidative stress, tissue hypoxia, angiogenesis and inflammation, female Fischer 344 rats were irradiated to the right hemithorax with a fractionated dose of 40 Gy (8 Gy x 5 days). The lung tissues were harvested before and at 4, 6, 10, 14, 18, 22 and 26 weeks after irradiation for serial studies of biological markers, including markers for hypoxia (HIF1alpha, pimonidazole and CA IX), oxidative stress (8-OHdG), and angiogenesis/capillary proliferation (VEGF/CD 105), as well as macrophage activation (ED-1) and cell signaling/fibrosis (NFkappaB, TGFbeta1), using immunohistochemistry and Western blot analysis. HIF1alpha staining could be observed as early as 4 weeks postirradiation and was significantly increased with time after irradiation. Importantly, HIF1alpha levels paralleled oxidative stress (8-OHdG), tissue hypoxia (pimonidazole and CA IX), and macrophage accumulation consistent with inflammatory response. Moreover, changes in HIF1alpha expression identified by immunohistochemistry assay parallel the changes in TGFbeta1, VEGF, NFkappaB and CD 105 levels in irradiated lungs. These results support the notion that oxidative stress and tissue hypoxia might serve as triggering signals for HIF1alpha activity in irradiated lungs, relating to radiation-induced inflammation, angiogenesis and fibrosis.
Characterization of Helicobacter pylori γ-Glutamyltranspeptidase Reveals the Molecular Basis for Substrate Specificity and a Critical Role for the Tyrosine 433-Containing Loop in Catalysis, (2007)

Helicobacter pylori gamma-glutamyltranspeptidase (HpGT) is a member of the N-terminal nucleophile hydrolase superfamily. It is translated as an inactive 60 kDa polypeptide precursor that undergoes intramolecular autocatalytic cleavage to generate a fully active heterodimer composed of a 40 kDa and a 20 kDa subunit. The resultant N-terminus, Thr 380, has been shown to be the catalytic nucleophile in both autoprocessing and enzymatic reactions. Once processed, HpGT catalyzes the hydrolysis of the gamma-glutamyl bond in glutathione and its conjugates. To facilitate the determination of physiologically relevant substrates for the enzyme, crystal structures of HpGT in complex with glutamate (1.6 A, Rfactor = 16.7%, Rfree = 19.0%) and an inactive HpGT mutant, T380A, in complex with S-(nitrobenzyl)glutathione (1.55 A, Rfactor = 18.7%, Rfree = 21.8%) have been determined. Residues that comprise the gamma-glutamyl binding site are primarily located in the 20 kDa subunit and make numerous hydrogen bonds with the alpha-amino and alpha-carboxylate groups of the substrate. In contrast, a single hydrogen bond occurs between the T380A mutant and the remainder of the ligand. Lack of specific coordination beyond the gamma-glutamyl moiety may account for the substrate binding permissiveness of the enzyme. Structural analysis was combined with site-directed mutagenesis of residues involved in maintaining the conformation of a loop region that covers the gamma-glutamyl binding site. Results provide evidence that access to this buried site may occur through conformational changes in the Tyr 433-containing loop, as disruption of the intricate hydrogen-bond network responsible for optimal placement of Tyr 433 significantly diminishes catalytic activity.
On the Role of the Nitroxyl Molecule in the Reaction of Hydrogen Atoms with Nitric Oxide (1965)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOn the Role of the Nitroxyl Molecule in the Reaction of Hydrogen Atoms with Nitric OxideF. C. Kohout and F. W. LampeCite this: J. Am. Chem. Soc. 1965, 87, 24, 5795–5796Publication Date (Print):December 1, 1965Publication History Published online1 May 2002Published inissue 1 December 1965https://pubs.acs.org/doi/10.1021/ja00952a052https://doi.org/10.1021/ja00952a052research-articleACS PublicationsRequest reuse permissionsArticle Views125Altmetric-Citations63LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A Vaccine Encoding Conserved Promiscuous HIV CD4 Epitopes Induces Broad T Cell Responses in Mice Transgenic to Multiple Common HLA Class II Molecules (2010)

Current HIV vaccine approaches are focused on immunogens encoding whole HIV antigenic proteins that mainly elicit cytotoxic CD8+ responses. Mounting evidence points toward a critical role for CD4+ T cells in the control of immunodeficiency virus replication, probably due to cognate help. Vaccine-induced CD4+ T cell responses might, therefore, have a protective effect in HIV replication. In addition, successful vaccines may have to elicit responses to multiple epitopes in a high proportion of vaccinees, to match the highly variable circulating strains of HIV. Using rational vaccine design, we developed a DNA vaccine encoding 18 algorithm-selected conserved, "promiscuous" (multiple HLA-DR-binding) B-subtype HIV CD4 epitopes - previously found to be frequently recognized by HIV-infected patients. We assessed the ability of the vaccine to induce broad T cell responses in the context of multiple HLA class II molecules using different strains of HLA class II- transgenic mice (-DR2, -DR4, -DQ6 and -DQ8). Mice displayed CD4+ and CD8+ T cell responses of significant breadth and magnitude, and 16 out of the 18 encoded epitopes were recognized. By virtue of inducing broad responses against conserved CD4+ T cell epitopes that can be recognized in the context of widely diverse, common HLA class II alleles, this vaccine concept may cope both with HIV genetic variability and increased population coverage. The vaccine may thus be a source of cognate help for HIV-specific CD8+ T cells elicited by conventional immunogens, in a wide proportion of vaccinees.
Suspended Planar Phospholipid Bilayers on Micromachined Supports (2000)

Micromachined structures consisting of an aperture between a buried reservoir and ambient have been produced using the photoresist SU8. The external surface of the structure, surrounding the aperture, was coated in a gold layer to allow surface modification with self-assembled monolayers. These structures were assessed as substrates for the assembly of “suspended” phospholipid bilayers. We report that phospholipid bilayer membranes could be formed over such apertures and that they are highly resistive to the conduction of metal anions (K+). Resistance values are typically found to be ∼1010 Ω (∼106 Ω cm2). These values represent a significant improvement over our membranes supported directly on gold substrates (105 Ω cm2). Fluorescence microscopy images are presented to provide evidence that the lipid bilayer spans the 100 μm aperture. Given the ease of producing large numbers of devices using microlithographic techniques, the proposed structures could form a sensing element for studying membrane transport phenomena in general and for ion-channel assays in particular.
The transmembrane serine protease (TMPRSS3) mutated in deafness DFNB8/10 activates the epithelial sodium channel (ENaC) in vitro (2002)

TMPRSS3 encodes a transmembrane serine protease that contains both LDLRA and SRCR domains and is mutated in non-syndromic autosomal recessive deafness (DFNB8/10). To study its function, we cloned the mouse ortholog which maps to Mmu17, which is structurally similar to the human gene and encodes a polypeptide with 88% identity to the human protein. RT-PCR and RNA in situ hybridization on rat and mouse cochlea revealed that Tmprss3 is expressed in the spiral ganglion, the cells supporting the organ of Corti and the stria vascularis. RT-PCR on mouse tissues showed expression in the thymus, stomach, testis and E19 embryos. Transient expression of wild-type or tagged TMPRSS3 protein showed a primary localization in the endoplasmic reticulum. The epithelial amiloride-sensitive sodium channel (ENaC), which is expressed in many sodium-reabsorbing tissues including the inner ear and is regulated by membrane-bound channel activating serine proteases (CAPs), is a potential substrate of TMPRSS3. In the Xenopus oocyte expression system, proteolytic processing of TMPRSS3 was associated with increased ENaC mediated currents. In contrast, 6 TMPRSS3 mutants (D103G, R109W, C194F, W251C, P404L, C407R) causing deafness and a mutant in the catalytic triad of TMPRSS3 (S401A), failed to undergo proteolytic cleavage and activate ENaC. These data indicate that important signaling pathways in the inner ear are controlled by proteolytic cleavage and suggest: (i) the existence of an auto-catalytic processing by which TMPRSS3 would become active, and (ii) that ENaC could be a substrate of TMPRSS3 in the inner ear.
Cutting Edge: Direct Suppression of B Cells by CD4+CD25+ Regulatory T Cells (2005)

Regulatory T cells (Tregs) can potentially migrate to the B cell areas of secondary lymphoid tissues and suppress T cell-dependent B cell Ig response. T cell-dependent Ig response requires B cell stimulation by Th cells. It has been unknown whether Tregs can directly suppress B cells or whether they must suppress Th cells to suppress B cell response. We report here that Foxp3+ Tregs are found in T-B area borders and within germinal centers of human lymphoid tissues and can directly suppress B cell Ig response. Although Tregs can effectively suppress T cells, they can also directly suppress B cell response without the need to first suppress Th cells. The direct suppression of B cell Ig production by Tregs is accompanied by inhibition of Ig class switch recombination.
c-Jun N-terminal kinase 1 defective CD4+CD25+FoxP3+ cells prolong pancreatic allograft survival in type 1 diabetic mice (2017)

Abstract CD4+CD25+FoxP3+ cells (Tregs) inhibit inflammatory immune responses to allografts. Here we found that co-transplantation of allogeneic pancreatic islets with Tregs that are defective in JNK1 signaling prolong the islet allograft survival in the liver parenchyma of the T1D mice. Deletion of the JNK1 in Tregs increased the expression of anti-apoptotic molecules Mcl-1, Bcl-Xl and anti-inflammatory cytokine IL-10 production. JNK1−/− Tregs persist for long period in the transplanted liver and prolong the islet allograft survival compared to WT Tregs. JNK1−/− Tregs demonstrated improved control of allo-inflammation compared to WT Tregs in the T1D liver upon co-transplantation. JNK1−/− Tregs specifically inhibit IL-17 and IL-21 medited alloimmune response. Inhibition of alloimmune response by JNK1−/− Tregs independently mediated through the LAG3 on its cell surface and the increased production of IL-10. Our study identifies a novel role of JNK1 signaling in the Tregs function and co-transplantation of JNK1 deficient Tregs enhances the islet allograft survival in the liver parenchyma of T1D mice.
An Antiviral Mechanism of Nitric Oxide (1999)

Although nitric oxide (NO) kills or inhibits the replication of a variety of intracellular pathogens, the antimicrobial mechanisms of NO are unknown. Here, we identify a viral protease as a target of NO. The life cycle of many viruses depends upon viral proteases that cleave viral polyproteins into individual polypeptides. NO inactivates the Coxsackievirus protease 3C, an enzyme necessary for the replication of Coxsackievirus. NO S-nitrosylates the cysteine residue in the active site of protease 3C, inhibiting protease activity and interrupting the viral life cycle. Substituting a serine residue for the active site cysteine renders protease 3C resistant to NO inhibition. Since cysteine proteases are critical for virulence or replication of many viruses, bacteria, and parasites, S-nitrosylation of pathogen cysteine proteases may be a general mechanism of antimicrobial host defenses.
New bipolar leads for the study of atrial arrhythmias. (1997)

The electrocardiography study of atrial arrhythmias has been hindered by the frequent occurrence of a "hidden". P wave in standard lead recordings. We present a modified method of surface electrocardiography that proved helpful in our prospective study of 26 consecutive patients in whom traditional surface recordings did not show the atrial mechanism. We recorded leads I, II, and III in their customary positions, except that we repositioned a pertinent limb electrode at a precordial site, in order to identify a P wave. The 4 alternative sites that we found most helpful were at the high and low parasternal positions, both to the right and to the left of the sternum. Confirmatory examples are submitted.
Apparent dispensability of the carbohydrate moiety of human interferon for antiviral activity. (1976)

Human leukocyte and tritium-labeled fibroblast interferons, prepared by induction with Sendai virus and with double-stranded polyinosinic acid.polycytidylic acid respectively, have been studied in relation to the carbohydrate moieties attached to them. These interferons were partially purified by immunoabsorbance and by gel filtration. On treatment with glycosidases, about 80% of the 3H-labeled sugar moieties in this glycoprotein-containing fraction was removed without detectable alteration of the antiviral activity or antibody-binding properties characteristic of interferon. The molecular weight of leukocyte interferon was reduced by about 4000. As others have reported, the heterogeneous character of interferon revealed by isoelectric focusing was greatly reduced by the enzyme treatment.
cDNA Expression Cloning of the IL-1 Receptor, a Member of the Immunoglobulin Superfamily (1988)

Interleukin-1 alpha and -1 beta (IL-1 alpha and IL-1 beta) are cytokines that participate in the regulation of immune responses, inflammatory reactions, and hematopoiesis. A direct expression strategy was used to clone the receptor for IL-1 from mouse T cells. The product of the cloned complementary DNA binds both IL-1 alpha and IL-1 beta in a manner indistinguishable from that of the native T cell IL-1 receptor. The extracellular, IL-1 binding portion of the receptor is 319 amino acids in length and is composed of three immunoglobulin-like domains. The cytoplasmic portion of the receptor is 217 amino acids long.
Proteomic pattern analysis discriminates among multiple sclerosis–related disorders (2011)

Our findings suggest that CSF proteomic pattern analysis can increase the accuracy of disease diagnosis of MS-related disorders and will aid physicians in appropriate therapeutic decision-making.