gebhart/patrepeval huggingface dataset:
The effects of androstenediol and dehydroepiandrosterone on the course and cytokine profile of tuberculosis in BALB/c mice (1998)

Immunity to Mycobacterium tuberculosis requires a T helper 1 (Th1) cytokine balance accompanied by tumour necrosis factor-alpha (TNF-alpha), and activated macrophages. These facets of the immune response are sensitive to suppression by glucocorticoids (GC), which can reactivate and exacerbate tuberculosis in man and animals. Dehydroepiandrosterone (DHEA) and its derivative, 3beta,17beta androstenediol (AED), are reported to have antiglucocorticoid properties in vivo. We therefore investigated the effects of predetermined optimal doses of these compounds, on the course of pulmonary tuberculosis in an established model in BALB/c mice in which an early phase of Th1-mediated response accompanied by adrenal hyperplasia, is followed by a switch to Th2, progressive loss of TNF-alpha expression and disease progression. Both compounds were protective, particularly AED which caused a fall in bacterial counts and prolonged survival. These effects correlated with the appearance within 3 days of cellular infiltrates rich in cells expressing interleukin-2 (IL-2), IL-1alpha and TNF-alpha, and with partial suppression of the switch to IL-4 producing cells that occurred in controls. AED also caused enhanced development of granulomas at 14 days, and persistence of granuloma formation to 120 days, with a corresponding suppression of areas affected by pneumonia. Much of the therapeutic effect of AED and DHEA was obtained by treating for only the first 3 weeks, which is the phase of adrenal hyperplasia. These results suggest that the ratio of GC to anti-GC steroids may play a role in the pathogenesis of tuberculosis, and further investigation could lead to novel treatment strategies.
Polarization effects in apertureless scanning near-field optical microscopy:?an experimental study (1999)

Strong electric-field enhancements at the apex of a tungsten tip illuminated by an external light source were recently predicted theoretically. We present an experimental study of the dependence of this effect on the polarization angle of the incident light. It is shown that the intensity of the light scattered by the tungsten tip of an apertureless scanning near-field optical microscope is 2 orders of magnitude higher when the incident light is p polarized than when it is s polarized. This experimental result is in good agreement with theoretical predictions and provides an easy way to test the quality of the tips.
Ig-Hepta, a Novel Member of the G Protein-coupled Hepta-helical Receptor (GPCR) Family That Has Immunoglobulin-like Repeats in a Long N-terminal Extracellular Domain and Defines a New Subfamily of GPCRs (1999)

A novel member of the G protein-coupled receptor (GPCR) family was cloned and characterized, which is unique, among the members, in its long extracellular domain comprising Ig-like repeats and in its high expression predominantly in the lung. The clone (Ig-Hepta) was first identified as a polymerase chain reaction product generated with primers designed to amplify secretin receptor family members including the parathyroid hormone-related peptide receptors. Analysis of the open reading frame of cDNAs isolated from a rat lung cDNA library indicated that Ig-Hepta is a protein of 1389 amino acid residues and has two Ig-like repeats in the N-terminal extracellular domain (exodomain) of 1053 amino acid residues and 7 transmembrane spans in the C-terminal region. Northern blot analysis revealed very high expression of its mRNA in the lung and low but detectable levels in the kidney and heart. The mRNA expression in the lung was found to be strongly induced postnatally. Biochemical analysis indicated that Ig-Hepta is a highly glycosylated protein and exists as a disulfide-linked dimer. Immunohistochemistry on rat lung and kidney sections revealed dense localization of Ig-Hepta in alveolar walls and intercalated cells in the collecting duct, respectively, suggesting a role in the regulation of acid-base balance. Ig-Hepta defines a new subfamily of GPCRs.
The double cubic lattice method: Efficient approaches to numerical integration of surface area and volume and to dot surface contouring of molecular assemblies (1995)

Abstract The double cubic lattice method (DCLM) is an accurate and rapid approach for computing numerically molecular surface areas (such as the solvent accessible or van der Waals surface) and the volume and compactness of molecular assemblies and for generating dot surfaces. The algorithm has no special memory requirements and can be easily implemented. The computation speed is extremely high, making interactive calculation of surfaces, volumes, and dot surfaces for systems of 1000 and more atoms possible on single‐processor workstations. The algorithm can be easily parallelized. The DCLM is an algorithmic variant of the approach proposed by Shrake and Rupley ( J. Mol. Biol. , 79 , 351–371, 1973). However, the application of two cubic lattices—one for grouping neighboring atomic centers and the other for grouping neighboring surface dots of an atom—results in a drastic reduction of central processing unit (CPU) time consumption by avoiding redundant distance checks. This is most noticeable for compact conformations. For instance, the calculation of the solvent accessible surface area of the crystal conformation of bovine pancreatic trypsin inhibitor (entry 4PTI of the Brookhaven Protein Data Bank, 362‐point sphere for all 454 nonhydrogen atoms) takes less than 1 second (on a single R3000 processor of an SGI 4D/480, about 5 MFLOP). The DCLM does not depend on the spherical point distribution applied. The quality of unit sphere tesselations is discussed. We propose new ways of subdivision based on the icosahedron and dodecahedron, which achieve constantly low ratios of longest to shortest arcs over the whole frequency range. The DCLM is the method of choice, especially for large molecular complexes and high point densities. Its speed has been compared to the fastest techniques known to the authors, and it was found to be superior, especially when also taking into account the small memory requirement and the flexibility of the algorithm. The program text may be obtained on request. © 1995 by John Wiley &amp; Sons, Inc.
Cancer initiating cells or cancer stem cells in the gastrointestinal tract and liver (2008)

It has been suggested that cancer stem cells population within the solid tumor with indefinite proliferation potential drives the growth and metastasis of cancer. In literature, these malignant stem cells also named Cancer initiating cells. Cancer stem cells exhibit low rate of division and proliferation in their niche that help them to avoid chemotherapy and radiation. Epithelial cancers are believed to originate from transformation of tissue stem cells. Bone marrow-derived cells, which are frequently recruited to sites of tissue injury and inflammation, might also represent a potential source of malignancy in the gastrointestinal tract. Pancreatic cancer is one of most common cause of cancer-related death. Pancreatic cancer stem cells have been characterized recently through serial transplantation of human pancreatic cancer cells. The phenotype of Pancreatic cancer stem cells has been defined as CD24(+)CD44(+)CD326 (ESA)(+). CD133 antigen has been also suggested as a potential marker for cancer stem cell in gastrointestinal tract but recently there is also debate in this regard. More recently, other cancer stem cells in gastrointestinal tract, such as colon cancer stem cells, liver cancer stem cells, have been also characterized in their phenotype. These advances clearly will bring the new strategy in cancer treatment and control in the gastrointestinal tract. In this review, the author will discuss the current status and progress about cancer stem cell research in gastrointestinal tract and liver.
Accurate Sensors Localization in Underground Mines or Tunnels (2015)

In this paper, a novel localization algorithm tailored for underground mines is proposed. Using the proposed algorithm, each regular (i.e position-unaware) node estimates its distances to the anchor (i.e., position-aware) nodes exploiting only its locally available information. Furthermore, a new hop count adjustment scheme, which complies with the labyrinthic nature of underground mines, is developed to ensure an accurate distance estimation, thereby making our localization algorithm more precise. Simulations show that our proposed algorithm, consistently outperforms in underground mines the best representative localization algorithms currently available in the literature in terms of
Twenty-Five Years of Quantitative PCR for Gene Expression Analysis (2008)

Following its invention 25 years ago, PCR has been adapted for numerous molecular biology applications. Gene expression analysis by reverse-transcription quantitative PCR (RT-qPCR) has been a key enabling technology of the post-genome era. Since the founding of BioTechniques, this journal has been a resource for the improvements in qPCR technology, experimental design, and data analysis. qPCR and, more specifically, real-time qPCR has become a routine and robust approach for measuring the expression of genes of interest, validating microarray experiments, and monitoring biomarkers. The use of real-time qPCR has nearly supplanted other approaches (e.g., Northern blotting, RNase protection assays). This review examines the current state of qPCR for gene expression analysis now that the method has reached a mature stage of development and implementation. Specifically, the different fluorescent reporter technologies of real-time qPCR are discussed as well as the selection of endogenous controls. The conceptual framework for data analysis methods is also presented to demystify these analysis techniques. The future of qPCR remains bright as the technology becomes more rapid, cost-effective, easier to use, and capable of higher throughput.
Safety and efficacy of bivalirudin monotherapy in patients with non-ST-segment elevation acute coronary syndromes with positive biomarkers undergoing percutaneous coronary intervention: a report from the Acute Catheterization and Urgent Intervention Triage Strategy trial (2019)

Compared with heparin plus GPI or bivalirudin plus GPI, bivalirudin monotherapy provides similar protection from ischemic events with less major bleeding at 30 days among patients with NSTE-ACS and positive biomarkers.
Cell Swelling and a Nonselective Cation Channel Regulated by Internal Ca2+and ATP in Native Reactive Astrocytes from Adult Rat Brain (2001)

Hypoxia-ischemia and ATP depletion are associated with glial swelling and blebbing, but mechanisms involved in these effects remain incompletely characterized. We examined morphological and electrophysiological responses of freshly isolated native reactive astrocytes (NRAs) after exposure to NaN(3), which depletes cellular ATP. Here we report that NaN(3) caused profound and sustained depolarization attributable to activation of a novel 35 pS Ca(2+)-activated, [ATP](i)-sensitive nonselective cation (NC(Ca-ATP)) channel, found in >90% of excised membrane patches. The channel was impermeable to Cl(-), was nearly equally permeable to monovalent cations, with permeabilities relative to K(+) being P(Cs)+/P(K)+(1.06) approximately P(Na)+/P(K)+(1.04) approximately P(Rb)+/P(K)+(1.02) approximately P(Li)+/P(K)+(0.96), and was essentially impermeable to Ca(2+) and Mg(2+) (P(Ca)2+/P(K)+ approximately P(Mg)2+/P(K)+ < 0.001), with intracellular Mg(2+) (100 microm to 1 mm) causing inward rectification. Pore radius, estimated by fitting relative permeabilities of organic cations to the Renkin equation, was 0.41 nm. This channel exhibited significantly different properties compared with previously reported NC(Ca-ATP) channels, including different sensitivity to block by various adenine nucleotides (EC(50) of 0.79 microm for [ATP](i), with no block by AMP or ADP), and activation by submicromolar [Ca](i). The apparent dissociation constant for Ca(2+) was voltage dependent (0.12, 0.31, and 1.5 microm at -40, -80, and -120 mV, respectively), with a Hill coefficient of 1.5. Channel opening by [ATP](i) depletion was accompanied by and appeared to precede blebbing of the cell membrane, suggesting participation of this channel in cation flux involved in cell swelling. We conclude that NRAs from adult rat brain express a 35 pS NC(Ca-ATP) channel that may play an important role in the pathogenesis of brain swelling.
Activation of murine B lymphocytes by Neisseria meningitidis and isolated meningococcal surface antigens (1983)

Heat-killed Neisseria meningitidis was found to be a potent mitogen for mouse splenic lymphocytes. Results obtained with different cell separation techniques indicated that the bacteria acted to selectively induce proliferation of B lymphocytes. First, partial or total depletion of T lymphocytes by treatment with various anti-T-cell antisera plus complement did not affect the ability of the remaining spleen cells to proliferate in response to N. meningitidis. Second, T lymphocytes purified by affinity chromatography through an immunoglobulin-antiimmunoglobulin-coated glass bead column were unresponsive to meningococcal stimulation, even when provided with a source of macrophages (irradiated or mitomycin C-treated spleen cells). Finally, treatment of spleen cells with soy bean agglutinin showed that, whereas the soy bean agglutinin-positive population (B-enriched lymphocytes) was highly responsive to stimulation by N. meningitidis, the soy bean agglutinin-negative population (T-enriched lymphocytes) displayed only a background level of proliferation when exposed to the bacteria. Isolated meningococcal surface antigens such as lipopolysaccharide (LPS) and outer membranes also possessed mitogenic activity and induced proliferation of B lymphocytes in a dose-dependent manner. Both LPS and non-LPS components contributed to the mitogenicity of outer membranes since the addition of outer membrane preparations to spleen cells from the low LPS responder C3H/HeJ mouse strain gave rise to a high level of proliferative activity.
Stability assessment on a library scale: a rapid method for the evaluation of the commutability and insertion of residues in C-terminal loops of the CH3 domains of IgG1-Fc (2013)

Antigen-binding Fc fragments (Fcab) are generated by engineering the C-terminal loop regions in the CH3 domain of human immunoglobulin G class 1-crystallizable fragment (IgG1-Fc). For an optimum library design with high percentage of well-folded clones for efficient binder selection, information about the correlation between primary structure and stability is needed. Here, we present a rapid method that allows determination of the overall stability of whole libraries of IgG1-Fc on the surface of yeast by flow cytometry. Libraries of IgG1-Fc mutants with distinct regions in AB-, CD- and EF-loops of the CH3 domains randomized or carrying therein insertions of five additional residues were constructed, incubated at increasing temperatures and probed for residual binding of generic Fc ligands. Calculated temperatures of half-maximal irreversible denaturation of the libraries gave a clear hierarchy of tolerance to randomization of distinct loop positions. Experimental data were evaluated by a computational approach and are discussed with respect to the structure of IgG1-Fc and variation in sequence and length of these loops in homologous Fc proteins. Generally, the described method allows for quick assessment of the effects of randomization of distinct regions on the foldability and stability of a yeast-displayed protein library.
Predicting the functional impact of protein mutations: application to cancer genomics (2011)

As large-scale re-sequencing of genomes reveals many protein mutations, especially in human cancer tissues, prediction of their likely functional impact becomes important practical goal. Here, we introduce a new functional impact score (FIS) for amino acid residue changes using evolutionary conservation patterns. The information in these patterns is derived from aligned families and sub-families of sequence homologs within and between species using combinatorial entropy formalism. The score performs well on a large set of human protein mutations in separating disease-associated variants (∼19 200), assumed to be strongly functional, from common polymorphisms (∼35 600), assumed to be weakly functional (area under the receiver operating characteristic curve of ∼0.86). In cancer, using recurrence, multiplicity and annotation for ∼10 000 mutations in the COSMIC database, the method does well in assigning higher scores to more likely functional mutations ('drivers'). To guide experimental prioritization, we report a list of about 1000 top human cancer genes frequently mutated in one or more cancer types ranked by likely functional impact; and, an additional 1000 candidate cancer genes with rare but likely functional mutations. In addition, we estimate that at least 5% of cancer-relevant mutations involve switch of function, rather than simply loss or gain of function.
Denaturing Gradient Gel Electrophoresis (DGGE): A Rapid and Sensitive Technique to Screen Nucleotide Sequence Variation in Populations (1999)

We describe a rapid and sensitive method for the detection of nucleotide sequence variation that can be used for large-scale screening of population markers. Denaturing gradient gel electrophoresis (DGGE) detects sequence variants of amplified fragments by the differences in their melting behavior. DGGE detects most single-base substitutions when carried out on products amplified with a primer to which a GC clamp has been added. Although DGGE has been primarily used for the detection of limited numbers of single-base mutations in disease studies, it offers great potential for use in population analysis of genetic markers with greater levels of sequence variation. The methodology described was developed to identify the number and distribution of MHC class I alpha 1 alleles among chinook salmon (Oncorhynchus tshawytscha) populations. DGGE detects 28 of 31 identified alpha 1 sequences, which differ by between 1 and 16 nucleotides and a two-codon indel. By creating a network of control alleles, 22-23 of the MHC alleles can be resolved rapidly and accurately by a single gel run condition, and 27 alleles can be resolved by two gel run conditions. This techniques has been used in surveys scoring alleles from two MHC markers (class I alpha 1 and alpha 2) in 20,000 individuals of chinook and coho (O. kisutch) salmon. A single person in our laboratory now analyzes 160 salmon from one MHC locus per day with DGGE.
Remote instrument diagnosis on the Internet (1998)

First AID (Automated Instrument Diagnostics) is a fault-diagnosis expert system that is based on an information client architecture. This expert system uses generic tools such as Web browsers to aid service engineers in remotely diagnosing the faults in LEO scanning electron microscopes (SEMs). The system lets engineers acquire information directly from the SEM, diagnose inaccurate behavior and remedy inappropriate instrument settings.
Roles of Metabotropic Glutamate Receptors in Brain Plasticity and Pathology (1995)

In summary, the mGluRs are a large family of receptor subtypes with diverse properties in terms of transduction coupling, pharmacology, and anatomical distribution. Many divergent studies have demonstrated that activation of these receptors can result in either neuroprotection or neuropathology. We hypothesized that the mGluRs of astrocytes may have a role in determining the response following administration of mGluR agonists in vivo, and we have defined a suitable in vitro model for the study of these receptors. The experimental plasticity demonstrated in the astrocyte culture model may represent a more general principle that conditions in the microenvironment may differentially alter mGluR subtype expression as part of development, functional specialization, or pathology. This astrocyte model of receptor regulation provides a system suitable for studying the effects of specific growth factors, neurotrophins, cytokines, and other substances released by neurons and glia that may act in both autocrine and paracrine fashions. Alteration in the ratios of receptors by such variables could then modify future signaling properties and neuroglial interactions, a form of conditioning of the astrocytic response that would alter the physiological output following glutamate release. One measure of the value of this model will be its usefulness in stimulating the generation of hypotheses that can be tested in vivo. For example, the morphology of the astrocytes when cultured in the defined medium has similarities to the morphology of astrocytes undergoing reactive gliosis in pathological states. It is also interesting to note that treatments that have been reported to increase excitatory amino acid-stimulated PI hydrolysis in ex vivo brain slices (lesions, ischemia, and kindling) are accompanied by reactive gliosis. Those findings combined with the present in vitro results lead us to speculate that mGluR5 expression may also be altered in vivo during reactive gliosis. If so, it will be important to examine the functional consequences of such a change with regard to the astrocytic response to injury and maintaining the balance between excitatory transmission and excitotoxicity.
Fermentation (2004)

Abstract Fermentation processes, products, and economic aspects are summarized according to the product classes of primary metabolites, secondary metabolites, biomass, enzymes (and whole cell biocatalysts), and biologicals. Although the information is focused on aerobic stirred tank processes, anaerobic, bubble column, and/or immobilized production techniques are referenced where applicable. Advantages of biochemical production over strictly synthetic processes are discussed. The history of fermentation is described at time periods of pre‐1700s, 1700s–1900, 1900–1945, 1945–1960, 1960–1970, 1970–1995, and 1995 to the present. This progression is followed by an overview of microbiological and fermentation principles, equipment requirements, inoculum development and scale‐up techniques, utilities, and regulatory considerations. Throughout this article specific product and process examples are included.
Nonspecific Suppression of [ 3 H]Thymidine Incorporation by "Control" Oligonucleotides (1992)

Phosphodiester oligonucleotides are rapidly degraded in spleen cell cultures. The present studies were conducted to determine whether thymidine released from degradation of such oligonucleotides could be reutilized and compete with [3H]thymidine incorporation, thereby causing nonspecific inhibition of "proliferation" assays. Our studies in mitogen-stimulated mouse spleen cells demonstrate that "control" oligonucleotides that contain thymidine can cause more than 90% inhibition of [3H]thymidine incorporation. This inhibitory effect was generally dependent on the location of the thymidine within the oligonucleotide: oligonucleotides that had 3'-terminal thymidine(s) caused more suppression than those in which thymidines were at the 5' end. All oligonucleotides caused a modest but variable inhibition of [3H]uridine incorporation. Furthermore, [3H]thymidine incorporation was partially inhibited even by oligonucleotides that did not contain thymidine. We propose that investigators who use [3H]thymidine incorporation assays to assess antisense effects do so with caution. It may be prudent to use control oligonucleotides with the same number and location of thymidine bases and to confirm [3H]thymidine incorporation assays with other measures of cell proliferation.