gebhart/patrepeval huggingface dataset:
The tricarboxylic acid cycle of Helicobacter pylori (1999)

The composition and properties of the tricarboxylic acid cycle of the microaerophilic human pathogen Helicobacter pylori were investigated in situ and in cell extracts using [1H]- and [13C]-NMR spectroscopy and spectrophotometry. NMR spectroscopy assays enabled highly specific measurements of some enzyme activities, previously not possible using spectrophotometry, in in situ studies with H. pylori, thus providing the first accurate picture of the complete tricarboxylic acid cycle of the bacterium. The presence, cellular location and kinetic parameters of citrate synthase, aconitase, isocitrate dehydrogenase, alpha-ketoglutarate oxidase, fumarate reductase, fumarase, malate dehydrogenase, and malate synthase activities in H. pylori are described. The absence of other enzyme activities of the cycle, including alpha-ketoglutarate dehydrogenase, succinyl-CoA synthetase, and succinate dehydrogenase also are shown. The H. pylori tricarboxylic acid cycle appears to be a noncyclic, branched pathway, characteristic of anaerobic metabolism, directed towards the production of succinate in the reductive dicarboxylic acid branch and alpha-ketoglutarate in the oxidative tricarboxylic acid branch. Both branches were metabolically linked by the presence of alpha-ketoglutarate oxidase activity. Under the growth conditions employed, H. pylori did not possess an operational glyoxylate bypass, owing to the absence of isocitrate lyase activity; nor a gamma-aminobutyrate shunt, owing to the absence of both gamma-aminobutyrate transaminase and succinic semialdehyde dehydrogenase activities. The catalytic and regulatory properties of the H. pylori tricarboxylic acid cycle enzymes are discussed by comparing their amino acid sequences with those of other, more extensively studied enzymes.
Expression of the normal p53 gene induces differentiation of K562 cells. (1992)

The multistep nature of human cancers is well illustrated by chronic myelogenous leukemia (CML), a clonal hematologic malignancy with two distinct phases: chronic and acute. Transition between these phases is characterized by unregulated growth and loss of differentiation of myeloid cells and their progenitors. We recently reported that loss of normal p53 expression correlates with transition from the chronic to acute phase in at least 25% of cases of CML. However, the precise relationship between this loss and biologic features of acute-phase CML is uncertain. To study this question, we artificially expressed normal p53 in K562, an erythroid acute-phase CML cell line lacking normal p53 expression. Biological effects were assessed by determining several growth parameters and by measuring synthesis of hemoglobin, a feature of mature erythroid cells. K562 cells expressing normal p53 had an increased proportion of cells in G1 versus S + G2, a longer doubling time and a lower growth saturation density than control K562 cells or K562 cells with antisense p53. Cells with normal p53 also expressed up to 50-fold more hemoglobin than controls. These data are consistent with the notion that loss of p53 expression may be responsible for many of the features of acute-phase CML cells. The data also demonstrate direct involvement of p53 in differentiation processes.
Total Synthesis and Biological Evaluation of Halipeptins A and D and Analogues (2006)

The marine-derived halipeptins A (1a) and D (1d) and their analogues 3a, 3d and 4a, 4d were synthesized starting from building blocks 10, 13, 14a or 14d, 15, and 16. The first strategy for assembling the building blocks, involving a macrolactamization reaction to form the 16-membered ring hydroxy thioamide 52d as a precursor, furnished the epi-isoleucine analogue (4d) of halipeptin D, whereas a second approach involving thiazoline formation prior to macrolactamization led to a mixture of halipeptins A (1a) and D (1d) and their analogues 3a, 3d (epimers at the indicated site) and 4a, 4d (epimers at the indicated site). The same route starting with D-Ala resulted in the exclusive formation of the epimeric halipeptin D analogue 3d. The synthesized halipeptins, together with the previously constructed oxazoline analogues 5d and 6d, were subjected to biological evaluation revealing anti-inflammatory properties for 1a, 1d, and 6d while being noncytotoxic against human colon cancer cells (HCT-116).
Enzymatic Removal of Free and Conjugated Sterols Forming Pitch Deposits in Environmentally Sound Bleaching of Eucalypt Paper Pulp (2006)

Free and conjugated sterols are among the main compounds responsible for pitch deposition in the manufacture of wood chemical pulps, making difficult the implementation of totally chlorine free bleaching (TCF) and closure of bleach plant circuits. In this work, the suitability of oxidative enzymes in efficiently removing sterols from eucalypt pulps is revealed. The enzymatic treatment was applied as an additional stage of an industrial-type TCF sequence for bleaching eucalypt kraft pulp. The pulp obtained after oxygen delignification was treated with a high-redox potential and thermostable fungal laccase using 1-hydroxybenzotriazole as an enzyme mediator. This pulp was further submitted to chelation and peroxide stages and compared with a control TCF pulp obtained using chemical reagents. The composition of the lipophilic extractives in the pulps and the corresponding liquids after the different stages was analyzed by gas chromatography and gas chromatography--mass spectrometry. Free sitosterol and sitosterol esters and glucosides, the major lipophilic compounds in eucalypt pulps, were completely removed during the laccase-mediator treatment. Only some intermediate products from sitosterol oxidation remained after the laccase stage, as well as in the final pulp. Pulp brightness was also improved due to the simultaneous removal of lignin by the laccase-mediator treatment.
A sensitive scanning technology for low frequency nuclear point mutations in human genomic DNA (2000)

Knowledge of the kinds and numbers of nuclear point mutations in human tissues is essential to the understanding of the mutation mechanisms underlying genetic diseases. However, nuclear point mutant fractions in normal humans are so low that few methods exist to measure them. We have now developed a means to scan for point mutations in 100 bp nuclear single copy sequences at mutant fractions as low as 10(-6). Beginning with about 10(8) human cells we first enrich for the desired nuclear sequence 10,000-fold from the genomic DNA by sequence-specific hybridization coupled with a biotin-streptavidin capture system. We next enrich for rare mutant sequences 100-fold against the wild-type sequence by wide bore constant denaturant capillary electrophoresis (CDCE). The mutant-enriched sample is subsequently amplified by high fidelity PCR using fluorescein-labeled primers. Amplified mutant sequences are further enriched via two rounds of CDCE coupled with high fidelity PCR. Individual mutants, seen as distinct peaks on CDCE, are then isolated and sequenced. We have tested this approach by measuring N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced point mutations in a 121 bp sequence of the adenomatous polyposis coli gene (APC) in human lymphoblastoid MT1 cells. Twelve different MNNG-induced GC-->AT transitions were reproducibly observed in MNNG-treated cells at mutant fractions between 2 x 10(-6) and 9 x 10(-6). The sensitivity of this approach was limited by the fidelity of Pfu DNA polymerase, which created 14 different GC-->TA transversions at a mutant fraction equivalent to approximately 10(-6) in the original samples. The approach described herein should be general for all DNA sequences suitable for CDCE analysis. Its sensitivity and capacity would permit detection of stem cell mutations in tissue sectors consisting of approximately 10(8) cells.
DNA Hybridization Assays Using Temperature Gradient Focusing and Peptide Nucleic Acids (2004)

Two types of DNA hybridization assays are demonstrated with temperature gradient focusing (TGF) and peptide nucleic acids (PNAs). In TGF, the application of a controlled temperature gradient along the length of a microchannel filled with an appropriate temperature-dependent buffer results in the formation of a gradient in both the electric field and electrophoretic velocity. Ionic species move in this gradient and concentrate at a unique point where the total velocity sums to zero. The first assay is a mixing assay in which PNA is allowed to flow through spatially focused DNA targets within a capillary. The second assay detects single base pair mutations (SBPM) by monitoring the fluorescence intensity of PNA/DNA duplexes as a function of temperature within the capillary. The SBPM analysis can be performed in less than 5 min with 100-fold more dilute analyte compared to conventional UV melting measurements.
Differential expression of p63 isoforms in normal tissues and neoplastic cells (2002)

The p63 gene encodes at least six different proteins with homology to the tumour suppressor protein p53 and the related p53 family member p73. So far, there have been limited data concerning the expression patterns of individual p63 proteins, due to a lack of reagents that distinguish between the different isoforms. Three antibodies have been produced specifically directed against the two N-terminal isoforms (TAp63 and DeltaNp63) and the C-terminal region of the p63alpha proteins. TAp63 proteins are located suprabasally in stratified epithelia compared with the N-terminal truncated forms, which are more abundantly expressed in the basal cell layer, indicating a switch in expression of p63 isoforms during normal cellular differentiation. Analysis of squamous cell carcinomas shows DeltaNp63alpha to be the most widely expressed isoform, compatible with a role for this protein in promoting neoplastic cell growth in these tissues. DeltaNp63 protein expression is also restricted to basal cells in breast and prostate, whilst TAp63 isoforms are more widely expressed in these tissues as well as in tumours at these sites. TAp63, but not DeltaNp63 or p63alpha, is detected in normal colon and in colon carcinoma. TAp63 proteins are also expressed in the nuclei of a sub-population of lymphoid cells and in most malignant lymphomas, whereas DeltaNp63 proteins are not expressed. Taken together, a hitherto unrecognized regulation of p63 isoform expression in vivo has been uncovered, with different p63 proteins expressed during differentiation and in different cell types. The data indicate roles for specific p63 isoforms not only in maintaining epithelial stem cell populations, but also in cellular differentiation and neoplasia.
Quantitating the subtleties of microglial morphology with fractal analysis (2013)

It is well established that microglial form and function are inextricably linked. In recent years, the traditional view that microglial form ranges between "ramified resting" and "activated amoeboid" has been emphasized through advancing imaging techniques that point to microglial form being highly dynamic even within the currently accepted morphological categories. Moreover, microglia adopt meaningful intermediate forms between categories, with considerable crossover in function and varying morphologies as they cycle, migrate, wave, phagocytose, and extend and retract fine and gross processes. From a quantitative perspective, it is problematic to measure such variability using traditional methods, but one way of quantitating such detail is through fractal analysis. The techniques of fractal analysis have been used for quantitating microglial morphology, to categorize gross differences but also to differentiate subtle differences (e.g., amongst ramified cells). Multifractal analysis in particular is one technique of fractal analysis that may be useful for identifying intermediate forms. Here we review current trends and methods of fractal analysis, focusing on box counting analysis, including lacunarity and multifractal analysis, as applied to microglial morphology.
Interleukin 12 potentiates the curative effect of a vaccine based on interleukin 2-transduced tumor cells. (1996)

The purpose of these studies was to determine whether systemic administration of recombinant interleukin 12 (rIL-12) is able to potentiate an initial, but insufficient T-cell antitumor response. Mice challenged with carcinoma cells engineered to release interleukin 2 (IL-2) and displaying such a response received single or multiple i.p. injections of rIL-12. This combination of systemic rIL-12 and local IL-2 increased the percentage of mice that rejected two different IL-2 gene-transduced tumors. In another set of experiments more closely resembling a clinical situation, IL-2 gene-transduced tumors were used as vaccines in an attempt to cure mice bearing wild-type parental tumors. The combination of these vaccines with systemic rIL-12 cured mice more effectively than rIL-12 and IL-2 gene-transduced tumor vaccines alone.
Sequential production of Th1 and Th2 cytokines in response to live bacillus Calmette-Guérin. (1995)

Causes of individual variation in susceptibility to mycobacterial diseases are only partly understood. An efficient cell-mediated immune response is crucial for resistance. Macrophages and T cells interact to eliminate the mycobacteria, partially through the effects of secreted cytokines. A vigorous anti-bacterial inflammatory response is sometimes accompanied by severe tissue damage, while immunosuppression leads to progressive infection. Here, live, attenuated Mycobacterium bovis, bacillus Calmette-Guérin (BCG), was used as a model antigen to study cytokine production at the single-cell level in response to mycobacteria. Peripheral blood mononuclear cells from healthy individuals were challenged in vitro and the kinetics and frequencies of cytokine-producing cells were studied by immunofluorescent visualization of intracellular cytokines. Fourteen cytokines were assayed; interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-1 receptor antagonist (IL-1ra), IL-2, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), TNF-beta and granulocyte-macrophage colony-stimulating factor (GM-CSF). A sequential production of T helper-1 (Th1) and T helper-2 (Th2) cytokines was induced by BCG. Early, at days 1-2 after stimulation, the response was dominated by monokines and a low IFN-gamma and TNF-beta production. At days 4-5 there was a marked production of Th1 lymphokines, with approximately 6% IFN-gamma+ cells, 4% TNF-beta+ cells and 2% IL-2+ cells. Late in the reaction, at days 10-12, a Th2 response with IL-4, IL-5 and IL-10 was detected, while the synthesis of Th1 lymphokines and monokines declined. Overall, our results provide further evidence of IFN-gamma as the major cytokine induced by mycobacteria in healthy individuals, but also suggest that Th2 cytokines participate in the response.
Small Interfering RNA Targeting RelB Protects Against Renal Ischemia-reperfusion Injury (2009)

Silencing RelB, using siRNA, can significantly attenuate IRI-induced renal dysfunction and protect mice against lethal kidney ischemia, highlighting the potential for siRNA-based clinical therapy.
Inflammation-activated Protein Kinases as Targets for Drug Development (2005)

Given the prevalence and debilitating nature of chronic inflammatory diseases, there is a never-ending quest to identify novel targets for the rational development of antiinflammatory drugs. The major signaling pathway that controls inflammation-associated gene expression is the one which leads to activation of transcription factor nuclear factor-kappaB. Therefore, inhibitors of the kinase responsible for nuclear factor-kappaB activation, IkappaB kinase, are expected to have potent antiinflammatory activity. Indeed, our results with cell type-specific inactivation of the beta-catalytic subunit of IkappaB kinase are by and large consistent with this assertion. In addition to IkappaB kinase and nuclear factor-kappaB, the expression of certain proinflammatory cytokines, such as interleukin-1 and tumor necrosis factor-alpha, is dependent on mitogen-activated protein kinases. Therefore, considerable attention has also been given to mitogen-activated protein kinases as likely targets for the development of novel antiinflammatory therapeutics. Preliminary preclinical data suggest that inhibitors that target all these pathways exhibit antiinflammatory activity. This review focuses on the possible mechanisms through which such inhibitors may interfere with inflammation and some of the complications that may be associated with their use.
Quantitative Determination of Metabolic Fluxes during Coutilization of Two Carbon Sources: Comparative Analyses with Corynebacterium glutamicum during Growth on Acetate and/or Glucose (2000)

Growth of Corynebacterium glutamicum on mixtures of the carbon sources glucose and acetate is shown to be distinct from growth on either substrate alone. The organism showed nondiauxic growth on media containing acetate-glucose mixtures and simultaneously metabolized these substrates. Compared to those for growth on acetate or glucose alone, the consumption rates of the individual substrates were reduced during acetate-glucose cometabolism, resulting in similar total carbon consumption rates for the three conditions. By (13)C-labeling experiments with subsequent nuclear magnetic resonance analyses in combination with metabolite balancing, the in vivo activities for pathways or single enzymes in the central metabolism of C. glutamicum were quantified for growth on acetate, on glucose, and on both carbon sources. The activity of the citric acid cycle was high on acetate, intermediate on acetate plus glucose, and low on glucose, corresponding to in vivo activities of citrate synthase of 413, 219, and 111 nmol. (mg of protein)(-1). min(-1), respectively. The citric acid cycle was replenished by carboxylation of phosphoenolpyruvate (PEP) and/or pyruvate (30 nmol. [mg of protein](-1). min(-1)) during growth on glucose. Although levels of PEP carboxylase and pyruvate carboxylase during growth on acetate were similar to those for growth on glucose, anaplerosis occurred solely by the glyoxylate cycle (99 nmol. [mg of protein](-1). min(-1)). Surprisingly, the anaplerotic function was fulfilled completely by the glyoxylate cycle (50 nmol. [mg of protein](-1). min(-1)) on glucose plus acetate also. Consistent with the predictions deduced from the metabolic flux analyses, a glyoxylate cycle-deficient mutant of C. glutamicum, constructed by targeted deletion of the isocitrate lyase and malate synthase genes, exhibited impaired growth on acetate-glucose mixtures.
Stromal expression of fibroblast activation protein/seprase, a cell membrane serine proteinase and gelatinase, is associated with longer survival in patients with invasive ductal carcinoma of breast (2001)

Fibroblast activation protein (FAP)/seprase is a serine integral membrane proteinase with gelatinase activity, which is expressed by activated fibroblasts in the stroma of various epithelial cancers, mesenchymal tumors and breast-cancer cells, as well as during wound repair. However, the pathophysiologic significance of its expression remains poorly understood. The present study was designed to reveal the impact of stromal expression of FAP/seprase on survival in human breast cancer. Immunohistochemical expression of FAP/seprase was restricted to stromal fibroblasts adjacent to tumor-cell nests but not cancer cells, which was confirmed by double-labeling immunohistochemistry. Clinicopathologic analysis revealed that more abundant FAP/seprase expression in 112 cases of invasive ductal carcinoma is associated with longer overall and disease-free survival. Multivariate analysis with other clinicopathologic factors demonstrated that FAP/seprase expression is an independent prognostic factor. The effect on the survival rate of FAP/seprase was also apparent in cases with lymph node metastasis. FAP/seprase expression is one of the manifestations of the stromal reaction (i.e., matrix turnover); thus, invasive ductal carcinomas with fewer stromal reactions expressing FAP/seprase may be more aggressive.
Plantas Nativas da Medicina Tradicional Brasileira: Uso Atual e Necessidade de Proteção (2006)

Apesar do secular emprego de muitas plantas nativas na medicina tradicional, raros são os exemplos de produtos registrados no Brasil com essas espécies. Neste estudo, são apresentados dados históricos e atuais sobre 23 plantas medicinais nativas do Brasil, usadas na medicina tradicional de Minas Gerais e inscritas na Farmacopéia Brasileira. O estudo mostra o quanto as empresas brasileiras e as dos demais países ricos em biodiversidade têm investido pouco no desenvolvimento e patenteamento de produtos da sua própria flora medicinal, confirmando a necessidade de estímulos à validação e proteção dessas plantas.
Expression cloning of beta 1,4 N-acetylgalactosaminyltransferase cDNAs that determine the expression of GM2 and GD2 gangliosides. (1992)

GM2 and GD2 gangliosides are sialic acid-containing glycosphingolipids expressed in some normal tissues such as brain and in various tumors such as neuroblastomas, astrocytomas, and malignant melanomas. We used a eukaryotic cell transient expression system to isolate cDNA clones that determine GM2 expression. We developed a new cell line from murine melanoma line B16 by transfecting with the polyoma T antigen gene that was suitable for this purpose. Two cDNA clones, both of which have a continuous open reading frame of 1683 base pairs, were isolated. Although the cloned cDNAs had no primary sequence similarity to reported glycosyltransferases, the deduced amino acid sequence predicted a type II transmembrane protein with an overall structure similar to other glycosyltransferases. The cDNA clones, when stably transfected, determined the expression of GM2 in B16 cells and GM2 and GD2 in the human melanoma line MeWo. Northern blot analysis revealed two transcripts in all cells that expressed either GM2 or GD2 or both. These findings indicate that the cDNAs catalyze the transfer of GalNAc onto GM3 and GD3 by a beta 1,4 linkage, resulting in the synthesis of GM2 and GD2, respectively. Namely they suggest that these cDNAs derive from the UDP-GalNAc: GM3/GD3 beta 1,4 N-acetylgalactosaminyltransferase (EC 2.4.1.92) gene.
Branch prediction for free (1993)

Many compilers rely on branch prediction to improve program performance by identifying frequently executed regions and by aiding in scheduling instructions. Profile-based predictors require a time-consuming and inconvenient compile-profile-compile cycle in order to make predictions. We present a program-based branch predictor that performs well for a large and diverse set of programs written in C and Fortran. In addition to using natural loop analysis to predict branches that control the iteration of loops, we focus on heuristics for predicting non-loop branches, which dominate the dynamic branch count of many programs. The heuristics are simple and require little program analysis, yet they are effective in terms of coverage and miss rate. Although program-based prediction does not equal the accuracy of profile-based prediction, we believe it reaches a sufficiently high level to be useful. Additional type and semantic information available to a compiler would enhance our heuristics.