gebhart/patrepeval huggingface dataset:
Review: The Interleukin‐23/Interleukin‐17 Axis in Spondyloarthritis Pathogenesis: Th17 and Beyond (2013)

Spondyloarthritis (SpA) represents a group of immune-mediated inflammatory diseases that exhibit overlapping clinical features, genetic predisposition, and pathogenic mechanisms (1), and affect 0.5–1.5% of the population (2). Disease can be undifferentiated, or manifest as reactive arthritis, psoriatic arthritis (PsA), arthritis associated with inflammatory bowel disease (IBD), or ankylosing spondylitis (AS). Enthesitis is an important pathologic feature of SpA, and contributes to both axial and peripheral arthritis, although synovitis also occurs. Structural damage in AS is dominated by new bone formation that can result in spinal fusion and marked functional limitation. Trabecular bone loss is also prominent, and paradoxically, occurs in close proximity to vertebral osteoproliferation. It can take years from the onset of symptoms to fulfill modified New York criteria for AS. Consequently, newer classification systems have been developed to identify individuals with early axial SpA (3,4) who may benefit from aggressive treatment.

Tumor necrosis factor inhibitors (TNFi) have had a major impact on the treatment of SpA (5). Their ability to reduce new bone formation in AS continues to be debated (6), although recent results are encouraging (7). TNFi are not beneficial in all patients, and thus there is a need for greater understanding of pathogenic mechanisms and translation of this knowledge into more effective therapies. Over the last decade our knowledge of the role of IL-23 and IL-17 cytokine pathways in immunity and immune-mediated inflammatory diseases, from multiple sclerosis (MS) to IBD, arthritis, and psoriasis has grown exponentially (8–11). For SpA, there has been a striking convergence of evidence from genetic studies (12–15), animal models (16–19), translational studies (20–23), and now a therapeutic trial (24) firmly implicating the IL-23/IL-17 axis in pathogenesis (25). In this review we outline key evidence accumulated over the last several years that forms the basis for this conclusion, and provides a background on which to build and refine models of pathogenesis, from inflammation to dysregulated bone formation. These developments, together with the availability of biologics and small molecules that target the IL-23/IL-17 axis, provide an unprecedented opportunity for advances in the treatment of SpA.
265 EFFECT OF SPECIFIC GRAVITY OF CULTURE MEDIUM ON IN VITRO EMBRYO DEVELOPMENT IN BUFFALO (2004)

In buffalo the success rate of transferable quality embryo production through in vitro procedure is very low as compared to cattle. Sub optimal culture conditions and physical conditions such as specific gravity of the culture medium may lead to a reduced rate of transferable buffalo embryo production from the oocytes matured and fertilized in vitro (Palta &amp; Chauhan,1998 Reprod. Fertil. Dev. 10, 379–391). This experiment was therefore conducted to find out the role of specific gravity of the IVC medium on the development rate of the buffalo embryos in vitro. Follicles of slaughter house ovaries were aspirated and the collected oocytes with cumulus-oocytes complexes (COCs) were cultured in TCM-199 medium supplemented with 10% fetal calf serum, 10% buffalo follicular fluid and 0.5 µg mL-1 FSH in 5% CO2 incubator at 38.5°C. The matured oocytes were then inseminated with frozen-thawed buffalo semen suspended in BO medium. After 42 h of post-inseminations the cleavage rates were evaluated. The 2–4 cell-cleaved eggs (Day 2 of post-insemination) were randomly divided and cultured for eight days in vitro in 1) modified synthetic fluid (mSOF) + 0.8 %BSA (control), 2) mSOF + 0.8 % BSA + gelatin (1 mg mL-1) 3) mSOF + 0.8% BSA + 1 mg mL-1 gelatin + 10 ng mL-1 epidermal growth factor (EGF). Supplementation of gelatin increased the specific gravity of the mSOF medium from 0.9658 ± 0.009 to 1.0331 ± 0.013 without any change in pH (7.4). The development of embryos to the 8–16 cell-stage on day 4 of in vitro culture were significantly higher (P &amp;lt; 0.05) in mSOF + 0.8% BSA + 1 mg mL-1 gelatin (81.8%; 27/33) than that in mSOF + 0.8% BSA (75.7%; 28/37) and mSOF + 0.8% BSA + 10 ng/mL EGF (68.7%; 22/32). When these embryos were further cultured for another four days (Day 8), the development of transferable quality embryos (morula/blastocyst) was 42.4% (14/33), 48.7% (18/37) and 46.9% (15/32), respectively. Supplementation of gelatin increased the cleavage of eggs up to the 8–16 cell-stage embryo, but did not significantly enhance the rate of development to the morula/blastocyst stage in comparison to control and EGF-supplemented group. However, the percentage of transferable quality embryos was slightly lower in the gelatin-added group but not statistically significant than other groups. The study concluded that increase in specific gravity of the in vitro culture medium enhanced initial cleavage rate but did not have any role in transferable embryo production in buffalo.
Pancreatic islet macroencapsulation using microwell porous membranes (2017)

Allogeneic islet transplantation into the liver in combination with immune suppressive drug therapy is widely regarded as a potential cure for type 1 diabetes. However, the intrahepatic system is suboptimal as the concentration of drugs and nutrients there is higher compared to pancreas, which negatively affects islet function. Islet encapsulation within semipermeable membranes is a promising strategy that allows for the islet transplantation outside the suboptimal liver portal system and provides environment, where islets can perform their endocrine function. In this study, we develop a macroencapsulation device based on thin microwell membranes. The islets are seeded in separate microwells to avoid aggregation, whereas the membrane porosity is tailored to achieve sufficient transport of nutrients, glucose and insulin. The non-degradable, microwell membranes are composed of poly (ether sulfone)/polyvinylpyrrolidone and manufactured via phase separation micro molding. Our results show that the device prevents aggregation and preserves the islet's native morphology. Moreover, the encapsulated islets maintain their glucose responsiveness and function after 7 days of culture (stimulation index above 2 for high glucose stimulation), demonstrating the potential of this novel device for islet transplantation.
Characterization of HIV-1 REV protein: binding stoichiometry and minimal RNA substrate (1991)

The HIV-1 REV protein binds to the stem II region of the REV-responsive element (RNA). Studies to further define the RNA sequence and structure specifically bound by REV protein identify a minimal RNA element of 40 nucleotides. Analysis of RNA fragments by gel retardation and filter binding suggest that a core element composed of one particular stem with flanking sequences capable of forming a second double stranded region is essential for specific recognition by REV protein. Stable REV-RNA complexes are formed in a stoichiometry of 1 REV: 1 RNA. The minimal RNA element binds 1 REV molecule while the stem II saturates at 3 REV molecules per RNA. These results establish that REV recognizes a primary binding site within the RRE and support the notion that the initial viral transcript binding event involves a monomeric REV protein.
Transcriptome analysis of mammary epithelial subpopulations identifies novel determinants of lineage commitment and cell fate (2008)

The mouse mammary epithelium is composed of three main cell types with distinct gene expression patterns. These suggest the existence of a novel functional cell type within the gland, that the basal/myoepithelial cells are key regulators of paracrine signalling and that there is a complex network of differentially expressed transcription factors controlling mammary epithelial cell fate. These data will form the basis for understanding not only cell fate determination and cellular homeostasis in the normal mammary epithelium but also the contribution of different mammary epithelial cell types to the etiology and molecular pathology of breast disease.
The pharmacological management of depression. (1986)

Antidepressants, given in the correct dosage and for an adequate period of time, are very effective in the treatment of the majority of cases of primary depressive illness. In this review, a rational approach to the pharmacological management of depression is discussed. The relative advantages and problems associated with the various types of antidepressants are reviewed. The role of benzodiazepines in the management of depression is considered.
Characterization of Commercially Available Vaginal Lubricants: A Safety Perspective (2014)

Vaginal lubricants are widely used by women to help solve intercourse difficulties or as enhancers, but recent reports raise questions about their safety. Twelve commercially available gel products were tested for pH value, pH buffering capacity, osmolality and cytotoxicity relevant to vaginal delivery. Obtained data were analyzed in light of the recent Advisory Note by the World Health Organization (WHO) for personal lubricants to be concomitantly used with condoms. Results showed that most products do not comply with pH and osmolality recommended standards, thus posing a potential hazard. Four products presented values of osmolality around three-times higher than the maximum acceptable limit of 1200 mOsm/kg. In vitro cell testing further identified substantial cytotoxicity even at 1:100 dilutions for three products, contrasting with no significant effect of up to at least a 1:5 dilution of a Universal Placebo gel. However, no direct correlation between these last results and pH or osmolality was found, thus suggesting that the individual toxicity of specific formulation components plays an important role in the outcome of a particular product. Although further assessment is required, these results highlight potential safety issues related to the formulation of commercially available vaginal lubricants.
Hormonal Signaling in Prostatic Hyperplasia and Neoplasia* (1999)

T PROSTATE is the site of two common diseases in aging men, benign prostatic hyperplasia (BPH) and prostate cancer (CaP). Although mortality rates due to BPH are less than 0.5 per 100,000 population, this disease affects the quality of life and health care costs exceed 4 billion dollars per year. If a man in the United States lives to be 80 yr of age, there is a 25% chance that he will require surgical treatment for BPH. In 1999, CaP will be diagnosed in 179,000 American men and it will cause 37,000 deaths. This represents the second most common cause of cancer deaths in men.
Ultrafast Click Conjugation of Macromolecular Building Blocks at Ambient Temperature (2009)

Block copolymers in seconds: Catalyst-free, ambient-temperature click conjugation of individual polymer strands becomes possible using novel ATRP-derived cyclopentadienyl-capped polymers in an extremely rapid hetero-Diels-Alder cycloaddition with macromolecules equipped with electron-deficient dithioester end groups prepared by the RAFT process.
Overexpression of Cyclin D1 Indicates a Poor Prognosis in Squamous Cell Carcinoma of the Head and Neck (1997)

These data provide evidence that overexpression of cyclin D1 protein in resection material of squamous cell carcinomas of the head and neck is indicative of a poor prognosis, independently of other known prognostic factors. Whether overexpression of cyclin D1 may therefore be used to select patients for more intensive treatment should be examined in the context of a clinical trial.
A high speed programming scheme for multi-level NAND flash memory (2002)

A new scheme for page programming of multi-level NAND flash memory has been developed. It maintains the 528 byte page size of 32 Mb NAND flash memories with a high throughput of 0.5 MB/s. The circuitry has been successfully implemented into an experimental 128 Mb multi-level flash memory.
Protease-Activated Receptors in Cardiovascular Diseases (2006)

Thrombosis associated with the pathophysiological activation of platelets and vascular cells has brought thrombin and its receptors to the forefront of cardiovascular medicine. Thrombin signaling through the protease-activated receptors (PARs) has been shown to influence a wide range of physiological responses including platelet activation, intimal hyperplasia, inflammation, and maintenance of vascular tone and barrier function. The thrombin receptors PAR1 and PAR4 can be effectively targeted in animals in which acute or prolonged exposure to thrombin leads to thrombosis and/or restenosis. In the present study, we describe the molecular and pharmacological basis of small-molecule inhibitors that target PAR1. In addition, we discuss a new class of cell-penetrating inhibitors, termed pepducins, that provide insight into previously unidentified roles of PAR1 and PAR4 in protease signaling.
Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure (2005)

Diuretics are frequently required to treat fluid retention in patients with congestive heart failure (CHF). Unfortunately, they can lead to a decline in renal function, electrolyte depletion, and neurohumoral activation. Arginine vasopressin (AVP) promotes renal water reabsorption via the V2 receptor, and its levels are increased in CHF. This study was designed to assess the effects of a single oral dose of tolvaptan, a selective V2-receptor blocker, in the absence of other medications, on renal function in human CHF and to compare this to the effects of a single oral dose of furosemide. We hypothesized that V2-receptor antagonism would yield a diuresis comparable to furosemide but would not adversely affect renal hemodynamics, plasma electrolyte concentration, or neurohumoral activation in stable human CHF. Renal and neurohumoral effects of tolvaptan and furosemide were assessed in an open-label, randomized, placebo-controlled crossover study in 14 patients with NYHA II-III CHF. Patients received placebo or 30 mg of tolvaptan on day 1 and were crossed over to the other medication on day 3. On day 5, all subjects received 80 mg of furosemide. Tolvaptan and furosemide induced similar diuretic responses. Unlike tolvaptan, furosemide increased urinary sodium and potassium excretion and decreased renal blood flow. Tolvaptan, furosemide, and placebo did not differ with respect to mean arterial pressure, glomerular filtration rate, or serum sodium and potassium. We conclude that tolvaptan is an effective aquaretic with no adverse effects on renal hemodynamics or serum electrolytes in patients with mild to moderate heart failure.
Monoclonal Antibody FC-5.01, Directed Against CD63 Antigen, is Internalized into Cytoplasmic Vesicles in the IIB-BR-G Human Breast Cancer Cell Line (1998)

Monoclonal antibody (MAb) FC-5.01, raised against the undifferentiated breast cancer cell line IIB-BR-G, has been recently shown to react with CD63. The antigen (Ag) recognized by MAb FC-5.01 is expressed in plasma membranes of IIB-BR-G and other neoplastic cells, as well as in activated platelets and endothelial cells, as detected by indirect immunofluorescence performed at 4 degrees C on live cells. In permeabilized cells, MAb FC-5.01 colocalizes with acridine orange in acidic vesicles (lysosomal/endosomal compartment). Scatchard plot analysis performed on IB-BR-G cells demonstrated a 1.4+/-0.4 x 10(7) M(-1) affinity constant and 2.1 x 10(6) antigenic sites per cell. MAb FC-5.01 is not able to mediate C fixation or ADCC toward CD63+ cells, but the FC-5.01-CD63 complex is efficiently internalized into cytoplasmic vesicles, as shown by an acid wash immunofluorescence assay. Cellular catabolism of the antibody bound by IIB-BR-G cells was studied using [125I]-FC-5.01. At 18 h, >70% of the radioactivity was present in the supernatant as degraded fragments (TCA-soluble). After internalization, rapid Ag re-expression could be demonstrated in IIB-BR-G cells. MAb FC-5.01 diminished migration of CD63+ cells in a Boyden chamber assay. Some of the above-mentioned properties would enable the use of MAb FC-5.01 as a vehicle to target different compounds inside CD63+ cells.
Genetic Influences on Cost-Efficient Organization of Human Cortical Functional Networks (2011)

The human cerebral cortex is a complex network of functionally specialized regions interconnected by axonal fibers, but the organizational principles underlying cortical connectivity remain unknown. Here, we report evidence that one such principle for functional cortical networks involves finding a balance between maximizing communication efficiency and minimizing connection cost, referred to as optimization of network cost-efficiency. We measured spontaneous fluctuations of the blood oxygenation level-dependent signal using functional magnetic resonance imaging in healthy monozygotic (16 pairs) and dizygotic (13 pairs) twins and characterized cost-efficient properties of brain network functional connectivity between 1041 distinct cortical regions. At the global network level, 60% of the interindividual variance in cost-efficiency of cortical functional networks was attributable to additive genetic effects. Regionally, significant genetic effects were observed throughout the cortex in a largely bilateral pattern, including bilateral posterior cingulate and medial prefrontal cortices, dorsolateral prefrontal and superior parietal cortices, and lateral temporal and inferomedial occipital regions. Genetic effects were stronger for cost-efficiency than for other metrics considered, and were more clearly significant in functional networks operating in the 0.09-0.18 Hz frequency interval than at higher or lower frequencies. These findings are consistent with the hypothesis that brain networks evolved to satisfy competitive selection criteria of maximizing efficiency and minimizing cost, and that optimization of network cost-efficiency represents an important principle for the brain's functional organization.
Modeling of solvent evaporation from polymer jets in electrospinning (2011)

Solvent evaporation plays a critical role in nanofiber formation in electrospinning. Here, we present a nonlinear mass diffusion-transfer model describing the drying process in dilute polymer solution jets. The model is used to predict transient solvent concentration profiles in polyacrylonitrile/N,N-dimethylformamide (PAN/DMF) jets with the initial radii ranging from 50 μm down to 100 nm. Numerical simulations demonstrate high transient inhomogeneity of solvent concentration over the jet cross-section in microscopic jets. The degree of inhomogeneity decreases for finer, submicron jets. The simulated jet drying time decreases rapidly with the decreasing initial jet radius, from seconds for microjets to single milliseconds for nanojets. The results demonstrate the need for further improved coupled multiphysics models of electrospinning jets.
Heterozygosity for a Surfactant Protein C Gene Mutation Associated with Usual Interstitial Pneumonitis and Cellular Nonspecific Interstitial Pneumonitis in One Kindred (2002)

Familial pulmonary fibrosis is a heterogeneous group of interstitial lung diseases of unknown cause that is associated with multiple pathologic subsets. Mutations in the surfactant protein C (SP-C) gene (SFTPC) are associated with familial desquamative and nonspecific interstitial pneumonitis. Genetic studies in familial usual interstitial pneumonitis have been inconclusive. Using a candidate gene approach, we found a heterozygous exon 5 + 128 T-->A transversion of SFTPC in a large familial pulmonary fibrosis kindred, including adults with usual interstitial pneumonitis and children with cellular nonspecific interstitial pneumonitis. The mutation is predicted to substitute a glutamine for a conserved leucine residue and may hinder processing of SP-C precursor protein. SP-C precursor protein displayed aberrant subcellular localization by immunostaining. Electron microscopy of affected lung revealed alveolar type II cell atypia, with numerous abnormal lamellar bodies. Mouse lung epithelial cells transfected with the SFTPC mutation were notable for similar electron microscopy findings and for exaggerated cellular toxicity. We show that an SFTPC mutation segregates with the pulmonary fibrosis phenotype in this kindred and may cause type II cellular injury. The presence of two different pathologic diagnoses in affected relatives sharing this mutation indicates that in this kindred, these diseases may represent pleiotropic manifestations of the same central pathogenesis.
A Single Amino Acid Change (Substitution of the Conserved Glu-590 with Alanine) in the C-terminal Domain of Rat Liver Carnitine Palmitoyltransferase I Increases its Malonyl-CoA Sensitivity Close to That Observed with the Muscle Isoform of the Enzyme (2003)

Carnitine palmitoyltransferase I (CPTI) catalyzes the conversion of long-chain fatty acyl-CoAs to acylcarnitines in the presence of l-carnitine. To determine the role of the highly conserved C-terminal glutamate residue, Glu-590, on catalysis and malonyl-CoA sensitivity, we separately changed the residue to alanine, lysine, glutamine, and aspartate. Substitution of Glu-590 with aspartate, a negatively charged amino acid with only one methyl group less than the glutamate residue in the wild-type enzyme, resulted in complete loss in the activity of the liver isoform of CPTI (L-CPTI). A change of Glu-590 to alanine, glutamine, and lysine caused a significant 9- to 16-fold increase in malonyl-CoA sensitivity but only a partial decrease in catalytic activity. Substitution of Glu-590 with neutral uncharged residues (alanine and glutamine) and/or a basic positively charged residue (lysine) significantly increased L-CPTI malonyl-CoA sensitivity to the level observed with the muscle isoform of the enzyme, suggesting the importance of neutral and/or positive charges in the switch of the kinetic properties of L-CPTI to the muscle isoform of CPTI. Since a conservative substitution of Glu-590 to aspartate but not glutamine resulted in complete loss in activity, we suggest that the longer side chain of glutamate is essential for catalysis and malonyl-CoA sensitivity. This is the first demonstration whereby a single residue mutation in the C-terminal region of the liver isoform of CPTI resulted in a change of its kinetic properties close to that observed with the muscle isoform of the enzyme and provides the rationale for the high malonyl-CoA sensitivity of muscle CPTI compared with the liver isoform of the enzyme.
Fecal microbiota transplantation: techniques, applications, and issues. (2012)

Fecal microbiota transplantation (FMT) has gained widespread recognition in light of the recent Clostridium difficile infection (CDI) epidemic, responsible for almost 110,000 deaths per year. The procedure's success rate has caused experts to reflect on what other conditions may benefit. This article provides an overview of (1) description and history of FMT, (2) FMT publications in CDI, (3) the concept of the gut microbiota as a virtual organ, (4) rationale for FMT use, (5) FMT use in inflammatory bowel disease, (6) emerging FMT applications, (7) how FMT is currently performed, and (8) how FMT may be performed in the future.
Objective Evaluation of Demethylchlortetracycline Hydrochloride in the Treatment of Acne (1966)

Ninety-four patients with inflammatory acne were treated with demethylchlortetracycline hydrochloride in a doubleblind, modified, crossover study. Good to excellent responses were obtained in 58% of the patients receiving demethylchlortetracycline, and in 24% of those receiving placebo. The drug, when used in a dosage of 150 mg three times daily without concomitant therapy, primarily affected inflammatory papules and pustules. Response to treatment was determined by counting lesions on the involved sites.