gebhart/patrepeval huggingface dataset:
Lipopolysaccharide-Activated B Cells Down-Regulate Th1 Immunity and Prevent Autoimmune Diabetes in Nonobese Diabetic Mice (2001)

B cells can serve dual roles in modulating T cell immunity through their potent capacity to present Ag and induce regulatory tolerance. Although B cells are necessary components for the initiation of spontaneous T cell autoimmunity to beta cell Ags in nonobese diabetic (NOD) mice, the role of activated B cells in the autoimmune process is poorly understood. In this study, we show that LPS-activated B cells, but not control B cells, express Fas ligand and secrete TGF-beta. Coincubation of diabetogenic T cells with activated B cells in vitro leads to the apoptosis of both T and B lymphocytes. Transfusion of activated B cells, but not control B cells, into prediabetic NOD mice inhibited spontaneous Th1 autoimmunity, but did not promote Th2 responses to beta cell autoantigens. Furthermore, this treatment induced mononuclear cell apoptosis predominantly in the spleen and temporarily impaired the activity of APCs. Cotransfer of activated B cells with diabetogenic splenic T cells prevented the adoptive transfer of type I diabetes mellitus (T1DM) to NOD/scid mice. Importantly, whereas 90% of NOD mice treated with control B cells developed T1DM within 27 wk, <20% of the NOD mice treated with activated B cells became hyperglycemic up to 1 year of age. Our data suggest that activated B cells can down-regulate pathogenic Th1 immunity through triggering the apoptosis of Th1 cells and/or inhibition of APC activity by the secretion of TGF-beta. These findings provide new insights into T-B cell interactions and may aid in the design of new therapies for human T1DM.
Handbook of Aqueous Electrolyte Thermodynamics (1986)

This handbook, describes the details of an electrolyte thermodynamics and the engineer's need for a source of recommended calculations and thermodynamic data either through recommended tabular values or annotated bibliographies which point to suitable sources. It provides a systematic presentation of electrolyte thermodynamics from basic definitions of equilibrium constants of ionic reactions to the prediction of activity coefficients of various species in multicomponent aqueous solutions of strong and/or weak electrolytes as well as the resulting phase equilibria calculative techniques. It is designed to assist the engineer in solving industrially important problems involving aqueous solutions of electrolytes and understanding the possible alternatives available as well as how they may be applied to solve problems either with available data or through available data prediction and analysis techniques. Several examples are used to illustrate the calculative techniques needed for the solution of different types of problems. Examples cited can be solved with limited computer facilities. Techniques can be expanded for the solution of more complex problems.
Effects of Vitamin D Metabolites and Analogues on Renal Function (1981)

The long-term effects of vitamin D analogues and metabolites on renal function were assessed in 24 patients with and without chronic renal failure. Treatment for periods of 5-45 months did not adversely affect renal function in 10 of 11 patients with stable renal function, although transient hypercalcaemia did cause transient rises in plasma creatinine. Of 13 patients with progressive renal failure before treatment, vitamin D-like compounds or the vehicle used for their administration may have accelerated renal failure in 3 patients independently of changes in plasma calcium or phosphate. Particular difficulties in assessing the effects of vitamin D-like compounds in progressive renal disease are discussed.
Minimized estradiol absorption with ultra-low-dose 10 μg 17β-estradiol vaginal tablets (2010)

During 12 weeks' administration, 10 microg vaginal tablets resulted in at least 50% lower mean estradiol concentrations than with the 25 microg dose within 24 h after dosing. Administering the 25 microg dose, mean E2 levels during the first 2 weeks exceeded the published reference range for postmenopausal women using the GCMS method, while, with the 10 microg dose, mean E2 levels remained in that range from the beginning, indicating minimized estradiol absorption.
Alternate Approaches to the Synthesis of 2′- O -Me Nucleosides (1995)

Abstract Three different approaches to the synthesis of 2′-O-methyl nucleosides starting from the corresponding nucleoside or commercially available 1,2:5,6-di-O-isopropylidene-α-D-allofuranose 1 are described.
The treatment of premature ejaculation: Psychological andbiological strategies (1998)

This review provides criteria for defining premature ejaculation (PE) and identifying men with this dysfunction. Included are discussions of possible PE subtypes and causes of PE. Furthermore, two empirically supported cognitive-behavioral approaches for treating PE are described and salient issues surrounding these types of treatment are considered. Biologically based treatments available to PE men are presented, with attention to the relative effectiveness and limitations of the various alternatives. Finally, a model illustrating factors relevant to determining the best therapeutic strategy is described, concluding with a brief discussion of the value of combining biological and psychological modes of treatment.
Antigenic Conservation of an Immunodominant Invariable Region of the VlsE Lipoprotein among European Pathogenic Genospecies ofBorrelia burgdorferiSL (2000)

Lyme disease is caused by genetically divergent spirochetes, including 3 pathogenic genospecies: Borrelia burgdorferi sensu stricto, B. garinii, and B. afzelii. Serodiagnosis is complicated by this genetic diversity. A synthetic peptide (C(6)), based on the 26-mer invariable region (IR(6)) of the variable surface antigen of B. burgdorferi (VlsE), was used as ELISA antigen, to test serum samples collected from mice experimentally infected with the 3 genospecies and from European patients with Lyme disease. Regardless of the infecting strains, mice produced a strong antibody response to C(6), which indicates that IR(6) is antigenically conserved among the pathogenic genospecies. Twenty of 23 patients with culture-confirmed erythema migrans had a detectable antibody response to C(6). A sensitivity of 95.2% was achieved, with serum samples collected from patients with well-defined acrodermatitis chronica atrophicans. Fourteen of 20 patients with symptoms of late Lyme disease also had a positive anti-IR(6) ELISA. Thus, it is possible that C(6) may be used to serodiagnose Lyme disease universally.
Revisiting the Role of First Trimester Homocysteine as an Index of Maternal and Fetal Outcome (2014)

AIM. To revisit the role of first trimester homocysteine levels with the maternal and fetal outcome. METHODS. This was a cohort study comprising 100 antenatal women between 8 and 12 weeks of gestation. Serum homocysteine levels were checked after overnight fasting. RESULTS. There were significantly elevated homocysteine levels among women with prior history of hypertensive disorders of pregnancy and prior second or third trimester pregnancy losses. There was no significant difference in homocysteine levels among women with previous gestational diabetes mellitus, preterm deliveries, or fetal malformations. Homocysteine levels were significantly elevated in those who developed hypertensive disorder of pregnancy, oligohydramnios, and meconium stained amniotic fluid, had a pregnancy loss, or delivered a low birth weight baby. There was no significant difference in homocysteine levels for those who developed gestational diabetes mellitus. CONCLUSIONS. Increased first trimester serum homocysteine is associated with history of pregnancy losses, hypertensive disorders of pregnancy, and preterm birth. This is also associated with hypertensive disorders of pregnancy, pregnancy loss, oligohydramnios, meconium stained amniotic fluid, and low birth weight in the current pregnancy. This trial is registered with ClinicalTrials.gov CTRI/2013/02/003441.
Retinal haemodynamics in individuals with well-controlled type 1 diabetes (2007)

Type 1 diabetic patients with no or minimal retinopathy who maintain relatively good glycaemic control do not show abnormalities of the retinal circulation at steady state, even after several years of diabetes. In such patients it may be necessary to test the vascular response to challenges to uncover any subtle abnormalities of the retinal vessels.
Synthesis and Characterization of Far‐Red/NIR‐Fluorescent BODIPY Dyes, Solid‐State Fluorescence, and Application as Fluorescent Tags Attached to Carbon Nano‐onions (2015)

A series of π-extended distyryl-substituted boron dipyrromethene (BODIPY) derivatives with intense far-red/near-infrared (NIR) fluorescence was synthesized and characterized, with a view to enhance the dye's performance for fluorescence labeling. An enhanced brightness was achieved by the introduction of two methyl substituents in the meso positions on the phenyl group of the BODIPY molecule; these substituents resulted in increased structural rigidity. Solid-state fluorescence was observed for one of the distyryl-substituted BODIPY derivatives. The introduction of a terminal bromo substituent allows for the subsequent immobilization of the BODIPY fluorophore on the surface of carbon nano-onions (CNOs), which leads to potential imaging agents for biological and biomedical applications. The far-red/NIR-fluorescent CNO nanoparticles were characterized by absorption, fluorescence, and Raman spectroscopies, as well as by thermogravimetric analysis, dynamic light scattering, high-resolution transmission electron microscopy, and confocal microscopy.
A genetic pathway for regulation of tra-2 translation (1997)

In Caenorhabditis elegans, the tra-2 sex-determining gene is regulated at the translational level by two 28 nt direct repeat elements (DREs) located in its 3' untranslated region (3'UTR). DRF is a factor that binds the DREs and may be a trans-acting translational regulator of tra-2. Here we identify two genes that are required for the normal pattern of translational control. A newly identified gene, called laf-1, is required for translational repression by the tra-2 3'UTR. In addition, the sex-determining gene, tra-3, appears to promote female development by freeing tra-2 from laf-1 repression. Finally, we show that DRF activity correlates with translational repression of tra-2 during development and that tra-3 regulates DRF activity. We suggest that tra-3 may promote female development by releasing tra-2 from translation repression by laf-1 and that translational control is important for proper sex determination--both in the early embryo and during postembryonic development.
Selective killing of K-ras mutant cancer cells by small molecule inducers of oxidative stress (2011)

Activating K-RAS mutations are the most frequent oncogenic mutations in human cancer. Numerous downstream signaling pathways have been shown to be deregulated by oncogenic K-ras. However, to date there are still no effective targeted therapies for this genetically defined subset of patients. Here we report the results of a small molecule, synthetic lethal screen using mouse embryonic fibroblasts derived from a mouse model harboring a conditional oncogenic K-ras(G12D) allele. Among the >50,000 compounds screened, we identified a class of drugs with selective activity against oncogenic K-ras-expressing cells. The most potent member of this class, lanperisone, acts by inducing nonapoptotic cell death in a cell cycle- and translation-independent manner. The mechanism of cell killing involves the induction of reactive oxygen species that are inefficiently scavenged in K-ras mutant cells, leading to oxidative stress and cell death. In mice, treatment with lanperisone suppresses the growth of K-ras-driven tumors without overt toxicity. Our findings establish the specific antitumor activity of lanperisone and reveal oxidative stress pathways as potential targets in Ras-mediated malignancies.
A single-site hydroxyapatite-bound zinc catalyst for highly efficient chemical fixation of carbon dioxide with epoxides (2005)

A zinc-based hydroxyapatite catalyst in conjunction with a Lewis base proved to be efficient for the coupling of CO2 and epoxide in the absence of additional organic solvents under an atmospheric CO2 pressure; the work-up procedure is straightforward and the catalyst could be reused without loss of catalytic activity and selectivity.
Hydrolysis and Condensation of Self-Assembled Monolayers of (3-Mercaptopropyl)trimethoxysilane on Ag and Au Surfaces (1997)

Self-assembled monolayer films of (3-mercaptopropyl)trimethoxysilane (3MPT) and their hydrolysis products on Ag and Au surfaces are characterized using Raman spectroscopy, FTIR spectroscopy, ellipsometry, X-ray photoelectron spectroscopy (XPS), and electrochemistry. 3MPT monolayers are formed through metal−thiolate bonding through the S atom on both metals, similar to other alkanethiol chemisorption chemistries. The orientation of 3MPT molecules in these monolayers is similar on both metals. Prior to hydrolysis, the molecules form an organized monolayer with the methoxy headgroups oriented largely parallel to the surface and the propyl chain in a largely trans conformation. When the methoxy groups are hydrolyzed, the 3MPT molecules cross-link through the formation of siloxane bonds. Although the surface vibrational spectroscopy indicates the presence of a small number of unreacted silanol groups on the siloxane surface, cyclic voltammetry of underpotential deposition of Pb suggests that the Si−O−Si network is highly cross-linked and relatively free from gross defects. The number of these unreacted silanols is estimated using XPS to be fewer than 5% of the original Si−O sites in the 3MPT monolayer.
Cultured dermal papilla cells induce follicle formation and hair growth by transdifferentiation of an adult epidermis (1992)

Adult rat pelage follicle dermal papilla cells induced follicle neogenesis and external hair growth when associated with adult footpad skin epidermis. They thus demonstrated a capacity to completely change the structural arrangement and gene expression of adult epidermis--an ability previously undocumented for cultured adult cells. Isolation chambers ensured that de novo follicle formation must have occurred by eliminating the possibility of cellular contributions, and/or inductive influences, from local skin follicles. These findings argue against previous suggestions of vibrissa follicle specificity, and imply that the potential for hair follicle induction may be common to all adult papilla cells.
Quantitative studies on SMN1 gene and carrier testing of spinal muscular atrophy. (2005)

SMN1 copy number could be detected precisely by real-time fluorescence quantitative PCR; the screening of gene carriers could provide essential data for genetic counseling.
A partition function algorithm for nucleic acid secondary structure including pseudoknots (2003)

Nucleic acid secondary structure models usually exclude pseudoknots due to the difficulty of treating these nonnested structures efficiently in structure prediction and partition function algorithms. Here, the standard secondary structure energy model is extended to include the most physically relevant pseudoknots. We describe an O(N(5)) dynamic programming algorithm, where N is the length of the strand, for computing the partition function and minimum energy structure over this class of secondary structures. Hence, it is possible to determine the probability of sampling the lowest energy structure, or any other structure of particular interest. This capability motivates the use of the partition function for the design of DNA or RNA molecules for bioengineering applications.
T cell receptor alpha/beta expressing double-negative (CD4-/CD8-) and CD4+ T helper cells in humans augment the production of pathogenic anti-DNA autoantibodies associated with lupus nephritis. (1989)

It is generally accepted that human Th cells express the surface glycoproteins CD4 and alpha/beta-chain heterodimer of the TCR whereas cytotoxic/suppressor cells are usually CD8+ and alpha/beta TCR+. Another minor set of T cells found in the periphery are CD4-/CD8- (double negative) and express the gamma/delta TCR; these cells can manifest MHC-restricted or nonrestricted cytotoxicity but no helper function. Herein we describe the existence of an unusual Th population in the peripheral blood of humans that are CD4-/CD8- and alpha/beta TCR+. These double-negative Th were markedly expanded in patients with the autoimmune disease SLE and along with CD4+ Th, they induced production of the pathogenic variety of anti-DNA autoantibodies that are IgG in class and cationic in charge. The cationic anti-DNA antibodies induced by the Th were markedly restricted in spectrotype indicating that an oligoclonal population of B cells were committed to produce the pathogenic autoantibodies in active lupus. IL-2-dependent T cell lines were also derived from the patients with active lupus nephritis but the majority of those T cell lines lacked pathogenic autoantibody-inducing capability. Only 4 out of 42 T cell lines from a lupus patient could induce the production of cationic IgG class anti-DNA autoantibodies. The phenotypes of the pathogenic autoantibody-inducing Th lines were similar to the Th subsets: CD4+, alpha/beta TCR+ or CD4-/CD8-, alpha/beta TCR+. These studies suggest that production of pathogenic autoantibodies in human lupus is mediated by mechanisms that are distinct from the generalized, nonspecific polyclonal B cell hyperactivity that leads to excessive production of natural autoantibodies.
Regulation of Thyroid Hormone Receptor Isoforms in Physiological and Pathological Cardiac Hypertrophy (2001)

Physiological and pathological cardiac hypertrophy have directionally opposite changes in transcription of thyroid hormone (TH)-responsive genes, including alpha- and beta-myosin heavy chain (MyHC) and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), and TH treatment can reverse molecular and functional abnormalities in pathological hypertrophy, such as pressure overload. These findings suggest relative hypothyroidism in pathological hypertrophy, but serum levels of TH are usually normal. We studied the regulation of TH receptors (TRs) beta1, alpha1, and alpha2 in pathological and physiological rat cardiac hypertrophy models with hypothyroid- and hyperthyroid-like changes in the TH target genes, alpha- and beta-MyHC and SERCA. All 3 TR subtypes in myocytes were downregulated in 2 hypertrophy models with a hypothyroid-like mRNA phenotype, phenylephrine in culture and pressure overload in vivo. Myocyte TRbeta1 was upregulated in models with a hyperthyroid-like phenotype, TH (triiodothyronine, T3), in culture and exercise in vivo. In myocyte culture, TR overexpression, or excess T3, reversed the effects of phenylephrine on TH-responsive mRNAs and promoters. In addition, TR cotransfection and treatment with the TRbeta1-selective agonist GC-1 suggested different functional coupling of the TR isoforms, TRbeta1 to transcription of beta-MyHC, SERCA, and TRbeta1, and TRalpha1 to alpha-MyHC transcription and increased myocyte size. We conclude that TR isoforms have distinct regulation and function in rat cardiac myocytes. Changes in myocyte TR levels can explain in part the characteristic molecular phenotypes in physiological and pathological cardiac hypertrophy.
Optical Response of Nanostructured Surfaces: Experimental Investigation of the Composite Diffracted Evanescent Wave Model (2006)

The past decade has seen a rapidly developing interest in the response of subwavelength-structured surfaces to optical excitation. Many studies have interpreted the optical coupling to the surface in terms of surface plasmon polaritons, but recently another approach involving diffraction of surface evanescent waves, the Composite Diffractive Evanescent Wave (CDEW) model has been proposed. We present here a series of measurements on very simple one-dimensional (1-D) subwavelength structures with the aim of testing key properties of the surface waves predicted by the CDEW model.
Picogram doses of lipopolysaccharide exacerbate antibody‐mediated thrombocytopenia and reduce the therapeutic efficacy of intravenous immunoglobulin in mice (2007)

Exacerbation of antibody-mediated thrombocytopenia following infection with viruses has recently been demonstrated in a mouse model of the disease. The phenomenon was caused by an increased activation of phagocytes through gamma-interferon secretion in response to infection. Endotoxins from Gram-negative bacteria are also known to be potent activators of phagocytic cells. The objective of the present work was to determine whether lipopolysaccharide (LPS) could exacerbate antibody-mediated thrombocytopenia in vivo and so alter the therapeutic efficacy of intravenous immunoglobulin (IVIg), using a mouse model of thrombocytopenia. Very low doses of LPS (picogram range) and of anti-platelet antibodies (nanogram range), which did not induce thrombocytopenia individually, could synergize in vivo, resulting in significant decreases in platelet counts. The therapeutic efficacy of IVIg in antibody-mediated thrombocytopenia was significantly reduced in presence of LPS. These in vivo observations further support a role for bacterial infections in the aetiology of immune thrombocytopenic purpura (ITP) and may contribute to better understand the recognized lack of efficacy of IVIg in a significant proportion of patients with ITP.
Dissociation of Antithrombotic Effect and Bleeding Time Prolongation in Rabbits by Inhibiting Tissue Factor Function (1997)

Inhibition of the tissue factor/factor VIIa (TF/F.VIIa) complex attenuates thrombosis in different animal models of arterial thrombosis. However, it remains unclear to what extent the antithrombotic effects are associated with changes in hemostatic functions and how this compares with inhibition of thrombin, an enzyme acting at a later stage in the coagulation cascade. The antithrombotic and the antihemostatic effects of a monoclonal anti-TF antibody (AP-1) were compared in a model of arterial thrombosis to those of a direct thrombin inhibitor (napsagatran) and heparin. In anesthetized rabbits transient arterial thrombi were induced by mechanical damage to the subendothelium of a moderately stenosed carotid artery. Recurrent formation and dislodgement of thrombi resulted in cyclic flow variations (CFVs) which were monitored over 2 hours. Rabbits received intravenously either a placebo (control), a monoclonal anti-rabbit TF antibody (AP-1, 0.05 mg/kg as an i.v. bolus repeated every 15 min, a specific low molecular weight thrombin inhibitor (napsagatran, 3 microg/kg/min) or heparin (3 and 13 microg/kg/min). The effect of the inhibitors on the hemostatic system was studied in a separate set of rabbits by measuring template bleeding times (BT) in the ear arterioles, marginal ear vein and the nail cuticle of the foreleg. AP-1 and napsagatran showed a similar antithrombotic activity (78% and 80% abolition of the CFVs, respectively), whereas either low or high dose heparin was poorly effective (43% and 40% inhibition of CFVs, respectively). At these antithrombotic doses and even at 4-fold higher dosage, AP-1 did not significantly alter the BT, whereas napsagatran and heparin prolonged the ear vessels and cuticle BT in a dose-dependent manner. These results suggest that in contrast to direct thrombin inhibition, the blockade of the TF/F. VIIa function did not result in a concomitant prolongation of the bleeding time. Thus, dissociation of antithrombotic and antihemostatic effects indicates that inhibition of the coagulation system at its initial stage represents a promising approach for the development of new anticoagulants.