gebhart/patrepeval huggingface dataset:
Modification of Proteins (1982)

Protein chemical modification is a problem-solving technique in research and technology. Modifications also occur in natural deteriorations. Generally these modifications are with the most reactive side chains and are predominantly oxidations, reductions, and nucleophilic and electrophilic substitutions. Deteriorations include peptide bond scissions, racemizations, β-eliminations, and formation of products by the reaction of proteins with added chemicals. Proteins are modified intentionally for structure-function relationship studies or for development of new and improved products. Although appearing quite varied, the techniques used in pharmacological, food and feed, or other industrial areas differ more operationally than from major differences in the levels of chemical sophistication that are used.
Properties and Metabolic Role of Mesaconate Hydratase of an Aerobic Bacterium1 (1977)

Journal Article Properties and Metabolic Role of Mesaconate Hydratase of an Aerobic Bacterium Get access Shintaro SUZUKI, Shintaro SUZUKI Department of Chemistry, Faculty of Science, Kyoto UniversitySakyo-ku, Kyoto, Kyoto 606 Search for other works by this author on: Oxford Academic PubMed Google Scholar Takashi OSUMI, Takashi OSUMI Department of Chemistry, Faculty of Science, Kyoto UniversitySakyo-ku, Kyoto, Kyoto 606 Search for other works by this author on: Oxford Academic PubMed Google Scholar Hirohiko KATSUKI Hirohiko KATSUKI Department of Chemistry, Faculty of Science, Kyoto UniversitySakyo-ku, Kyoto, Kyoto 606 Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Biochemistry, Volume 81, Issue 6, June 1977, Pages 1917–1925, https://doi.org/10.1093/oxfordjournals.jbchem.a131654 Published: 01 June 1977 Article history Received: 09 November 1976 Published: 01 June 1977
Localization of Xenopus Vg1 mRNA by Vera Protein and the Endoplasmic Reticulum (1997)

In many organisms, pattern formation in the embryo develops from the polarized distributions of messenger RNAs (mRNAs) in the egg. In Xenopus, the mRNA encoding Vg1, a growth factor involved in mesoderm induction, is localized to the vegetal cortex of oocytes. A protein named Vera was shown to be involved in Vg1 mRNA localization. Vera cofractionates with endoplasmic reticulum (ER) membranes, and endogenous Vg1 mRNA is associated with a subcompartment of the ER. Vera may promote mRNA localization in Xenopus oocytes by mediating an interaction between the Vg1 3' untranslated region and the ER subcompartment.
Tyrosine kinase inhibitors for non-small-cell lung cancer: finding patients who will be responsive (2011)

In recent years, the management of lung cancer has been moving towards molecular-guided treatment, and the best example of this new approach is the use of the tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib in patients with mutations in the epidermal growth factor receptor (EGFR). Erlotinib was introduced as a second- and third-line therapy for advanced non-small-cell lung cancer and demonstrated a survival advantage over placebo in unselected patients. Gefitinb did not confer the same advantage but specific subgroups of patients obtained higher response rates. The discovery of EGFR mutations explained the molecular mechanism of sensitivity to TKIs, and several clinical trials have evaluated the efficacy of TKIs in EGFR-mutated patients. New molecular alterations involving different genes have also been described and associated with sensitivity or resistance to TKIs. The identification of molecular predictors of response can allow the selection of patients who will be the most likely to respond to erlotinib and gefitinib.
Acidic fibroblast growth factor is a modulator of epithelial plasticity in a rat bladder carcinoma cell line. (1990)

During normal embryogenesis and neoplastic transformation epithelia change their state of differentiation and degree of cohesiveness. It is thus essential to identify the signals modulating these transitions. We report here that acidic fibroblast growth factor (FGF) induces cells derived from a rat bladder carcinoma to lose their epithelial character and to acquire some properties typical of mesenchymal cells. The structurally related basic FGF did not have such an effect; both factors, however, had a mitogenic activity for these cells. Two distinct populations of receptors for acidic FGF and basic FGF were distinguished by their ligand-binding characteristics. The observations that both acidic and basic FGFs had a mitogenic effect on NBT-II cells and that only acidic FGF caused cell dissociation and dispersion strongly suggest that these two biological activities could be medicated through distinct signaling pathways.
Real Time Destination Prediction Based On Efficient Routes (2006)

&lt;div class="htmlview paragraph"&gt;This paper presents a novel method for predicting the location of a driver's destination during the drive. Such a prediction can be used to help decide which information to automatically present to the driver, depending on where the driver is going. The prediction is based on the common intuition that drivers tend to chose efficient routes. We quantify this preference for efficiency probabilistically based on a database of driving trips we gathered with GPS receivers. We show how to use this probability along with a map of driving times to compute the probability of any candidate destination. Our tests show that halfway through the drive, we can predict the destination to within about 10 km, and at three quarters of the way, the error drops to about 3 km.&lt;/div&gt;
Methylation of glycosylated sphingolipid modulates membrane lipid topography and pathogenicity of Cryptococcus neoformans (2011)

In previous studies we showed that the replication of Cryptococcus neoformans in the lung environment is controlled by the glucosylceramide (GlcCer) synthase gene (GCS1), which synthesizes the membrane sphingolipid GlcCer from the C9-methyl ceramide. Here, we studied the effect of the mutation of the sphingolipid C9 methyltransferase gene (SMT1), which adds a methyl group to position 9 of the sphingosine backbone of ceramide. The C. neoformans Δsmt1 mutant does not make C9-methyl ceramide and, thus, any methylated GlcCer. However, it accumulates demethylated ceramide and demethylated GlcCer. The Δsmt1 mutant loses more than 80% of its virulence compared with the wild type and the reconstituted strain. Interestingly, growth of C. neoformans Δsmt1 in the lung was decreased and C. neoformans cells were contained in lung granulomas, which significantly reduced the rate of their dissemination to the brain reducing the onset of meningoencephalitis. Thus, using fluorescent spectroscopy and atomic force microscopy we compared the wild type and Δsmt1 mutant and found that the altered membrane composition and GlcCer structure affects fungal membrane rigidity, suggesting that specific sphingolipid structures are required for proper fungal membrane organization and integrity. Therefore, we propose that the physical structure of the plasma membrane imparted by specific classes of sphingolipids represents a critical factor for the ability of the fungus to establish virulence.
p73 and Reelin in Cajal-Retzius Cells of the Developing Human Hippocampal Formation (2004)

In the fetal human hippocampus, Cajal-Retzius (CR) cells coexpress p73, a p53-family member involved in cell survival and apoptosis, and the glycoprotein reelin, crucial for radial migration. We distinguish two populations of putative CR cells. (1). p73/reelin expressing cells appear around 10 gestational weeks (GW) at the cortico-choroid border in the temporal horn of the lateral ventricle (the ventral cortical hem) and occupy the marginal zone (MZ) overlying the ammonic and dentate primordia. (2). Additional p73-positive cells appear from 14 GW onward in the neuroepithelium near the dentate-fimbrial boundary and spread toward the pial surface, flanking the migrating secondary dentate matrix. From 13 to 17 GW, large parts of the dentate gyrus are almost devoid of CR cells. p73/Reelin-positive CR cells appear in the MZ of the suprapyramidal blade at 16 GW and around 21 GW in the infrapyramidal blade. The p73-positive cells of the dentate-fimbrial boundary express reelin when they are close to the pial surface, suggesting that they differentiate into CR cells of the infrapyramidal blade. Reelin-positive, p73-negative interneurons are prominent in the prospective strata lacunosum-moleculare and radiatum of cornu ammonis as early as 14 GW; in the dentate molecular layer and hilus they appear around midgestation. We propose that CR cells of the human hippocampal formation belong to two distinct cell populations: an early one derived from the ventral cortical hem and mainly related to migration of the ammonic and dentate plates and a later appearing one derived from the dentate-fimbrial neuroepithelium, which may be related to the protracted neurogenesis and migration of dentate granule cells, particularly of the infrapyramidal blade.
Anti-fibrinolytic use for minimising perioperative allogeneic blood transfusion (2007)

Anti-fibrinolytic drugs provide worthwhile reductions in blood loss and the need for allogeneic red cell transfusion. Based on the results of randomised trials their efficacy does not appear to be offset by serious adverse effects. In most circumstances the lysine analogues are probably as effective as aprotinin and are cheaper; the evidence is stronger for tranexamic acid than for aminocaproic acid. In high risk cardiac surgery, where there is a substantial probability of serious blood loss, aprotinin may be preferred over tranexamic acid. Aprotinin does not appear to be associated with an increased risk of vascular occlusion and death, but the data do not exclude an increased risk of renal failure. There is no need for further placebo-controlled trials of aprotinin or lysine analogues in cardiac surgery. The principal need is for large comparative trials to assess the relative efficacy, safety and cost-effectiveness of anti-fibrinolytic drugs in different surgical procedures.
Human natural killer cell expansion is regulated by thrombospondin- mediated activation of transforming growth factor-beta 1 and independent accessory cell-derived contact and soluble factors (1996)

Natural killer cells (NK) were studied to determine factors important in their expansion. Flourescence-activated cell sorter (FACS) purified CD56+/CD3- NK cells cultured alone for 18 days in rIL-2 containing medium (1,000 U/mL) showed enhanced cytotoxicity but only minimal expansion. NK expansion was increased (12.5 +/- 1.6-fold) by coculturing NK with soluble factors produced by irradiated peripheral blood mononuclear cells (PBMNC) in which the two populations were separated by a microporous membrane. However, maximal NK expansion was always observed when NK were cocultured in direct contact with irradiated PBMNC (49.4 +/- 5.9-fold). To determine if marrow stroma, which supports differentiation of primitive NK progenitors, was a better accessory cell population than irradiated PBMNC, NK were cocultured in direct contact with primary marrow stromal layers. NK expansion with marrow stroma was similar to PBMNC. Fibroblast cell lines (M2-10B4, NRK-49F, NIH-3T3) and human umbilical vein endothelial cells (HUVEC), all homogeneous populations and devoid of monocytes, also exhibited a similar contact-dependent increase in NK expansion. Experiments were designed using fixed M2-10B4 stromal cells to separate the contact-induced proliferative stimuli from soluble factors. NK plated directly on ethanol/acetic acid-fixed M2-10B4, which leaves stromal ligands (cell membrane components and ECM) intact, resulted in increased NK expansion compared with medium alone. We further show that the combination of independent contact and soluble factors is responsible for maximal late NK expansion (days 28 through 40) but paradoxically inhibits early NK expansion (day 7). The proliferation inhibitory effects were verified by 3H-thymidine uptake and could be detected at days 2 through 6 but no longer 14 days after the initiation of the culture. We show that both laminin and thrombospondin inhibit early NK proliferation, whereas only thrombospondin was capable of also stimulating late NK expansion. The effect of thrombospondin on early NK proliferation is related to activation of transforming growth factor-beta 1 (TGF-beta) because anti-TGF-beta neutralizing antibody completely abrogated thrombospondin-mediated inhibition of early NK proliferation. Although inhibitory early in culture, active TGF-beta added only at culture initiation increases late NK expansion similar to thrombospondin. TGF-beta was not present in the thrombospondin preparation but latent TGF-beta in serum, or TGF-beta transcripts identified in IL-2-activated NK could explain paracrine or autocrine mechanisms for the regulation of NK proliferation. Finally, anti-TGF-beta neutralizing antibody only minimally affects stroma-mediated inhibition of early NK proliferation suggesting that aside from thrombospondin/TGF-beta, additional contact factors are important for the regulation of NK proliferation.
Biosynthesis of a prostaglandin by a plant enzyme. (1978)

Lipoxygenase-2 from soybeans catalyzes the oxygenation of arachidonic acid to form significant amounts of a prostaglandin product. Results obtained with the dithionite-reduced derivatized product upon combined gas chromatography-mass spectroscopy are consistent with structures of the stereoisomers of 9,11,15-trihydroxyprosta-5,13-dienoic acid. A portion of the material formed by reduction of the enzyme product with dithionite reacts positively in a radioimmunoassay against rabbit anti-prostaglandin F2alpha antibody. This appears to be the first report of the synthesis of a prostaglandin by a non-animal enzyme.
A continuous-wave hybrid AlGaInAs-silicon evanescent laser (2006)

We report a novel laser architecture, the hybrid silicon evanescent laser (SEL), that utilizes offset AlGaInAs quantum wells (QWs) bonded to a silicon waveguide. The silicon waveguide is fabricated on a silicon-on-insulator wafer using a complimentary metal-oxide-semiconductor-compatible process, and is subsequently bonded with the AlGaInAs QW structure using low temperature O/sub 2/ plasma-assisted wafer bonding. The optical mode in the SEL is predominantly confined in the passive silicon waveguide and evanescently couples into the III-V active region providing optical gain. The SEL lases continuous wave (CW) at 1568 nm with a threshold of 23 mW. The maximum temperature for CW operation is 60/spl deg/C. The maximum single-sided fiber-coupled CW output power at room temperature is 4.5 mW.
Low density lipoprotein metabolism by human macrophages activated with low density lipoprotein immune complexes. A possible mechanism of foam cell formation. (1988)

Human macrophages play a key role in atherogenesis and are believed to be the progenitors of the cholesteryl ester (CE)-laden foam cells present in early atherosclerotic lesions. Several mechanisms by which macrophages accumulate CE have been recently described. One involves a perturbation in LDL metabolism subsequent to macrophage activation. Thus, we decided to study the effect of macrophage activation by immune complexes on N-LDL metabolism. Initially, LDL-containing immune complexes (LDL-IC) were chosen, since increased plasma levels of these IC have been reported in patients with coronary heart disease. Human macrophages stimulated for 22 h with LDL-IC (250 micrograms/ml) and incubated afterwards for 20 h with 10 micrograms/ml 125I-N-LDL showed a six- and fourfold increase in the accumulation and degradation, respectively, of 125I-N-LDL over the values observed in nonstimulated cells. Scatchard analysis of 125I-N-LDL-specific binding suggests an increase (20-fold) in the number of LDL receptors in macrophages stimulated with LDL-IC. We studied other immune complexes varying in size and antigen composition. Some of the IC were able to stimulate, although to a lesser degree, the uptake of N-LDL by macrophages. Lipoprotein IC are more efficient and have the greatest capacity to increase N-LDL uptake and CE accumulation. We conclude that human macrophage activation by LDL-IC leads to an increase in LDL receptor activity and promotes in vitro foam cell formation.
Micropharmacology of monoclonal antibodies in solid tumors: direct experimental evidence for a binding site barrier. (1992)

Monoclonal antibodies (MAbs) often distribute nonuniformly in tumors. In part, that observation reflects intrinsic heterogeneity within the tumor; in part, it reflects poor penetration through tumor substance. Several years ago, we proposed the "binding site barrier" hypothesis (J.N. Weinstein, R.R. Eger, D.G. Covell, C.D.V. Black, J. Mulshine, J.A. Carrasquillo, S.M. Larson, and A.M. Keenan, Ann. NY Acad. Sci., 507: 199-210, 1987; K. Fujimori, D.C. Covell, J.E. Fletcher, and J.N. Weinstein, Cancer Res., 49: 5656-5663, 1989), the idea that antibodies (and other ligands) could be prevented from penetrating tumors by the very fact of their successful binding to target antigen. Calculations suggested that this might be a significant factor in the therapy of even microscopic nodules. The higher the affinity and the higher the antigen density, the greater the barrier. Here, we provide direct experimental evidence of such a barrier to the percolation of D3 MAb through intradermally implanted line 10 carcinoma of guinea pigs. After affinity purification using glutaraldehyde-fixed line 10 cells, the D3 had an average immunoreactivity of 88%, a binding constant of 1.6 +/- 0.3 (SEM) x 10(10) M-1, and saturation binding of 355,000 +/- 15,000 molecules/cell. Using a combination of double-label autoradiography and double-chromagen immunohistochemistry, we determined simultaneously the distribution of (a) i.v. injected D3 MAb; (b) coinjected isotype-matched control IgG (BL3); (c) D3 antigen; (d) blood vessels. The previously developed mathematical models aided in the design of these experiments. Double immunochemical staining of the tumors showed antigen-rich patches 100-800 microns across, surrounded by blood vessels. At a low MAb dose (30 micrograms), binding to antigen severely hindered penetration into antigenic patches as small as 200 microns, even at 72 h. Explanation of this finding by a physical barrier was ruled out by the observation that BL3 distributed uniformly in the same patches. At a higher dose (1000 micrograms), the binding site barrier could be partially overcome. The same general principles of micropharmacology may apply to biological ligands other than antibodies, including those secreted by genetically modified cells.
Drug-metabolism research challenges in the new millennium: individual variability in drug therapy and drug safety. (1998)

One of the most challenging research areas in pharmacology in the new millennium is to understand why individuals respond differently to drug therapy and to what extent that individual variability in disposition is responsible for the observed differences in therapeutic efficacy and adverse reactions. To answer these complex questions, drug-metabolism research will rely on multidisciplinary approaches more than ever to investigate the many components involved in drug metabolism and disposition. Major research challenges include the following: (1) the genetic variation of drug targets (receptors, enzymes, etc.), drug transporters (multispecific organic anion transporter, P-glycoprotein, alpha-1-acid glycoprotein, etc.), and drug-metabolizing enzymes (cytochrome P450s and other enzymes); (2) the structure and function of all genetic variants of drug receptors, transporters, and metabolizing enzymes; (3) the induction, repression, and inhibition of all components involved in drug disposition; (4) the development of noninvasive in vivo methods to determine the physiological significance of various components in the handling of specific therapeutic agents in humans; (5) the mechanism of idiosyncratic adverse drug reactions; and (6) the pharmacokinetic and pharmacodynamic relationships to explain the individual differences in therapeutic efficacy and drug safety. Thus successful drug-metabolism research in the new millennium must integrate receptor biology, enzymology, recombinant DNA technology, biochemical toxicology, and drug disposition into study design and conduct balanced in vitro and in vivo experiments to allow a full understanding of the mechanisms of individual variability in drug therapy and drug safety.
Contractile Dysfunction Irrespective of the Mutant Protein in Human Hypertrophic Cardiomyopathy With Normal Systolic Function (2011)

Changes in sarcomere function reflect the clinical HCM phenotype rather than the specific MYBPC3 mutation. Hypocontractile sarcomeres are a common deficit in human HCM with normal systolic left ventricular function and may contribute to HCM disease progression.
The silicon/silica electrode (1980)

Electron flow between silicon and an aqueous solution through a thermally grown SiO2 layer is observed after a suitable activation process. The activation is either a heat treatment in vacuum or a negative bias applied to the silicon. The duration required for the cathodic bias is consistent with the time needed to provide a high positive ion density in the SiO2. As the SiO2 becomes more electronically conducting, copious hydrogen evolution begins. If metal ions such as zinc are present, they can be reduced giving metal deposits. If sufficiently high voltage is applied, cathodic luminescence, characteristic of the ions in solution, is observed. When the electronic conductivity is obtained, the system SiSiO2 behaves like a metal electrode, in that current is passed to reducing or oxidizing agents in solution when the electrode potential reaches the Eº for the redox couple. The results are explained in terms of field-aided ion diffusion into the oxide under the cathodic bias, occurring particularly at flaws in the oxide. The potential importance of the results in MOSFET quality control, in ISFET technology, and in basic models of anodic oxidation is discussed. Elektronenfluß zwischen Silizium und einer wäßrigen Lösung über eine Schicht thermisch gewachsenem SiO2 wird nach einem geeigneten Aktivierungsprozeß beobachtet. Die Aktivierung besteht entweder in einer Wärmebehandlung im Vakuum oder einer negativen Vorspannung am Silizium. Die notwendige Dauer für die negative Vorspannung stimmt mit der Zeit überein, die notwendig ist, um eine hohe positive Ionendichte im SiO2 zu schaffen. Wenn das SiO2 elektronisch stärker leitend wird, beginnt eine starke Wasserstoffentwicklung. Wenn Metallionen, wie z. B. Zink, vorhanden sind, können sie reduziert werden und dabei Metallniederschläge ergeben. Wenn eine genügend hohe Spannung angelegt wird, wird kathodische Lumineszenz, charakteristisch für die gelösten Ionen, beobachtet. Wenn die elektronische Leitfähigkeit einsetzt, verhält sich das System SiSiO2 wie eine Metallelektrode, in der Strom für die Reduktion oder Oxidation der gelösten Agenzien fließt, wenn das Elektrodenpotential den Wert Eº für das Redoxpaar erreicht. Die Ergebnisse werden mit der feldunterstützten Ionendiffusion in das Oxid unter kathodischer Vorspannung erklärt, die besonders an Oxiddefekten auftritt. Die mögliche Bedeutung der Ergebnisse für die Qualitätskontrolle von MOSFET's, für die ISFET-Technologie und für grundlegende Modelle der anodischen Oxidation wird diskutiert.