gebhart/patrepeval huggingface dataset:
Photochemically Patterned Poly(methyl methacrylate) Surfaces Used in the Fabrication of Microanalytical Devices (2005)

We report here the photochemical surface modification of poly(methyl methacrylate), PMMA, microfluidic devices by UV light to yield pendant carboxylic acid surface moieties. Patterns of carboxylic acid sites can be formed from the micrometer to millimeter scale by exposure of PMMA through a contact mask, and the chemical patterns allow for further functionalization of PMMA microdevice surfaces to yield arrays or other structured architectures. Demonstrated here is the relationship between UV exposure time and PMMA surface wettability, topography, surface functional group density, and electroosmotic flow (EOF) of aqueous buffer solutions in microchannels made of PMMA. It is found that the water contact angle on PMMA surfaces decreases from 70 degrees to 24 degrees after exposure to UV light as the result of the formation of carboxylic acid sites. However, upon rinsing with 2-propanol, the water contact angle increases to approximately 80 degrees , and this increase is attributed to changes in surface roughness resulting from removal of low molecular weight PMMA formed from scission events. In addition, the surface roughness and surface coverage of carboxylic acid groups exhibit a characteristic trend with UV exposure time. Electroosmotic flow (EOF) in PMMA microchannels increases upon UV modification and is pH dependent. The possible photolysis mechanism for formation of carboxylic acid groups on PMMA surfaces under the conditions outlined in this work is discussed.
Strategies for Tumor Elimination by Cytotoxic T Lymphocytes (1998)

Despite differences in their tissue of origin, many tumors share high level expression of certain tumor-associated proteins. Our laboratory has focused on the possibility of utilizing antigenic components of these proteins as a focus for T-cell immunotherapy of cancer. The advantage of targeting such commonly expressed proteins is the fact that such therapy could be of value in eliminating many different types of tumors. A potential barrier in the identification of T-cell epitopes derived from these proteins and presented by tumor cells is the fact that these proteins are also expressed at low levels in some normal tissues, and therefore, self-tolerance may eliminate T cells that are capable of recognizing these epitopes with high avidity. We have utilized two different murine model systems to explore the extent to which self-tolerance may limit the immune response to a tumor-specific antigen. The first compared the ability of mice deficient in expression of murine p53 (p53 knock-out mice) and normal mice, to respond against several epitopes of the p53 protein. The second model compares the ability of conventional mice with transgenic mice that express the influenza hemagglutinin in the periphery to respond to a dominant antigenic peptide of this transgene product. In both models we have investigated the effect self-tolerance has on elimination of tumors expressing the toleragen.
Effects of Helicobacter pylori Infection on Gastric Mucin Expression (2008)

These results suggest that H. pylori infection causes alterations of mucin expression, closely related with the development of gastric atrophy with intestinal metaplasia, probably contributing to carcinogenesis.
Hybrid binary-unary hardware accelerator (2019)

Stochastic computing has been used in recent years to create designs with significantly smaller area by harnessing unary encoding of data. However, the low area advantage comes at an exponential price in latency, making the area x delay cost unattractive. In this paper, we present a novel method which uses a hybrid binary / unary representation to perform computations. We first divide the input range into a few sub-regions, perform unary computations on each sub-region individually, and finally pack the outputs of all sub-regions back to compact binary. Moreover, we propose a synthesis methodology and a regression model to predict an optimal or sub-optimal design in the design space. The proposed method is especially well-suited to FPGAs due to the abundant availability of routing and flip-flop resources. To the best of our knowledge, we are the first to show a scalable method based on the principles of stochastic computing that can beat conventional binary in terms of a real cost, i.e., area x delay. Our method outperforms the binary and fully unary methods on a number of functions and on a common edge detection algorithm. In terms of area x delay cost, our cost is on average only 2.51% and 10.2% of the binary for 8- and 10-bit resolutions, respectively. These numbers are 2--3 orders of magnitude better than the results of traditional stochastic methods. Our method is not competitive with the binary method for high-resolution oscillating functions such as sin(15x).
Protective Effect of ACE Inhibitors on Ischemia-Reperfusion-induced Arrhythmias in Rats: Is this Effect Related to the Free Radical Scavenging Action of these Drugs? (1997)

The antiarrhythmic effects of captopril, a sulphydryl-containing angiotensin converting enzyme (ACE) inhibitor, were compared with those of the nonsulphydryl-containing ACE inhibitor lisinopril and the sulphydryl-containing agent glutathione in an in vivo rat model of coronary artery ligation. To produce arrhythmia, the left main coronary artery was occluded for 7 min, followed by 7 min of reperfusion. Captopril (3 mg kg-1) and lisinopril (0.1, 0.3 or 1 mg kg-1) caused marked decreases in mean arterial blood pressure (BP) and heart rate, whereas glutathione (5 mg kg-1) had no effect on them. The incidence of ventricular tachycardia (VT) on ischemia and reperfusion was significantly reduced by captopril and lisinopril. Captopril and 1 mg kg-1 lisinopril also significantly decreased the number of VEB during occlusion and the duration of VT on reperfusion, respectively. These drugs also attenuated the incidence of reversible ventricular fibrillation (VF) and the number of ventricular ectopic beats (VEB) during reperfusion. However, glutathione only reduced the incidence of VT on reperfusion, significantly. These results suggest that, in this experimental model, ACE inhibitors limit the arrhythmias following ischemia-reperfusion and free radical scavenging action of these drugs does not have a major contributory role in their protective effect.
A common pharmacophore for cytotoxic natural products that stabilize microtubules (1999)

Taxol (paclitaxel), a complex diterpene obtained from the Pacific yew, Taxus brevifolia, is arguably the most important new drug in cancer chemotherapy. The mechanism of cytotoxic action for paclitaxel-i.e., the stabilization of microtubules leading to mitotic arrest-is now shared by four recently identified natural products, eleutherobin, epothilones A and B, and discodermolide. Their ability to competitively inhibit [3H]paclitaxel binding to microtubules strongly suggests the existence of a common binding site. Recently, we have developed nonaromatic analogues of paclitaxel that maintain high cytotoxicity and tubulin binding (e.g., nonataxel). We now propose a common pharmacophore that unites paclitaxel, nonataxel, the epothilones, eleutherobin, and discodermolide, and rationalizes the extensive structure-activity relationship data pertinent to these compounds. Insights from the common pharmacophore have enabled the development of a hybrid construct with demonstrated cytotoxic and tubulin-binding activity.
Large-scale RNA-Seq Transcriptome Analysis of 4043 Cancers and 548 Normal Tissue Controls across 12 TCGA Cancer Types (2015)

Abstract The Cancer Genome Atlas (TCGA) has accrued RNA-Seq-based transcriptome data for more than 4000 cancer tissue samples across 12 cancer types, translating these data into biological insights remains a major challenge. We analyzed and compared the transcriptomes of 4043 cancer and 548 normal tissue samples from 21 TCGA cancer types and created a comprehensive catalog of gene expression alterations for each cancer type. By clustering genes into co-regulated gene sets, we identified seven cross-cancer gene signatures altered across a diverse panel of primary human cancer samples. A 14-gene signature extracted from these seven cross-cancer gene signatures precisely differentiated between cancerous and normal samples, the predictive accuracy of leave-one-out cross-validation (LOOCV) were 92.04%, 96.23%, 91.76%, 90.05%, 88.17%, 94.29% and 99.10% for BLCA, BRCA, COAD, HNSC, LIHC, LUAD and LUSC, respectively. A lung cancer-specific gene signature, containing SFTPA1 and SFTPA2 genes, accurately distinguished lung cancer from other cancer samples, the predictive accuracy of LOOCV for TCGA and GSE5364 data were 95.68% and 100%, respectively. These gene signatures provide rich insights into the transcriptional programs that trigger tumorigenesis and metastasis and many genes in the signature gene panels may be of significant value to the diagnosis and treatment of cancer.
Epitope Mapping (1998)

The aim of epitope mapping is to find out which part of its antigen a given antibody binds to, and mapping methods are most widely applied to protein antigens. It is possible to think of epitope mapping as a “simple” biochemical problem of finding out how one well-defined protein (a monoclonal antibody [MAb]) binds to another (the antigen). The term “epitope mapping” is also used to describe the attempt to determine all the major sites on a protein surface that can elicit an antibody response, at the end of which one might claim to have produced an “epitope map” of the protein antigen. This information might be very useful, for example, to someone wishing to produce antiviral vaccines. However, it is questionable how far one can go down this road, since the final map will depend on the individual immune response (although immunodominant regions undoubtedly exist) and on how MAbs are selected, and may depend also on the mapping method used. Epitope mapping is usually done with MAbs, though it can be done with polyclonal antisera in a rather less rigorous way, bearing in mind that antisera behave as a mixture of MAbs of variable complexity. Some authors have extended the epitope concept to the interaction between peptide hormones and their receptors (1); however one feels about this, it does make the point that in mapping epitopes, we are studying a biological process of fundamental importance, that of protein—protein interaction.
Unambiguous determination of the stereochemistry of nucleotidyl transfer catalyzed by DNA polymerase I from Escherichia coli (1981)

Nucleotidyl transfer catalyzed by DNA polymerase I from Escherichia coli proceeds with greater than 97% inversion of configuration at P alpha of the alpha-phosphorothioate analogue of dATP. This is shown by experiments in which dAMPS,18O2 is stereospecifically phosphorylated to (Sp)-dATP alpha S, alpha 18O2, which is then copolymerized with dTTP by DNA polymerase. The product of the polymerization is degraded to dAMPS,18O by methods that do not affect the configuration of the phosphorothioate. After the dAMPS,18O is stereospecifically phosphorylated, the resulting (Sp)-dATP alpha S, alpha 18O is copolymerized as before with dTTP. The 18O is found in the displaced pyrophosphate by mass spectral analysis and so must have been in the pyrophosphate bridge of (Sp)-dATP alpha S, alpha 18O. Since this 18O was originally non-bridging in (Sp)-dATP alpha S, alpha 18O2, the phosphorothioate configuration must have been inverted in the polymerization reaction. This confirms the determination of P. M. J. Burgers & F. Eckstein [(1979) J. Biol. Chem. 254, 6889-6893], who used kinetic correlations based on the stereoselectivity of snake venom phosphodiesterase to deduce the stereochemistry of this reaction.
Los españoles ante la justicia global (2009)

En el terreno de la justicia global, este estudio se interesa por conocer cuales son los criterios que los espanoles introducen a la hora de dibujar la sociedad global ideal, y tambien contrastarlos con las teorias y propuestas normativas de filosofos y analistas.
Manufacturing of half-tone phase-shift masks II: writing and process (1994)

A half-tone phase shift mask process has been developed. The writing and process for normal masks are found to be applicable to HT-PSMs. A dry etch process has been adopted to etch the shifter. Several characteristics of HT-PSMs such as CD uniformity, CD linearity, edge roughness and corner rounding, positional accuracy in the EB process, selectivity in dry etch, pattern profile, durability against cleaning, pelliclization and a blind pattern are evaluated. The process shows a good performance sufficient for first generation 64 MDRAM mask making. The EB writing causes no charge-up problem. The selectivity of HT-shifter to an i-line resist and an new type EB resist in dry etch is satisfactory and the selectivity to a fused silica substrate is more than 300. An exposure test was conducted with our HT-PSM. Coherency factor ((sigma) ) of a stepper is found to strongly affect the defocus range and exposure latitude.
Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects (2020)

Growing interest has been seen in using lysergic acid diethylamide (LSD) in psychiatric research and therapy. However, no modern studies have evaluated subjective and autonomic effects of different and pharmaceutically well-defined doses of LSD. We used a double-blind, randomized, placebo-controlled, crossover design in 16 healthy subjects (eight women, eight men) who underwent six 25 h sessions and received placebo, LSD (25, 50, 100, and 200 µg), and 200 µg LSD 1 h after administration of the serotonin 5-hydroxytryptamine-2A (5-HT<sub>2A</sub>) receptor antagonist ketanserin (40 mg). Test days were separated by at least 10 days. Outcome measures included self-rating scales that evaluated subjective effects, autonomic effects, adverse effects, plasma brain-derived neurotrophic factor levels, and pharmacokinetics up to 24 h. The pharmacokinetic-subjective response relationship was evaluated. LSD showed dose-proportional pharmacokinetics and first-order elimination and dose-dependently induced subjective responses starting at the 25 µg dose. A ceiling effect was observed for good drug effects at 100 µg. The 200 µg dose of LSD induced greater ego dissolution than the 100 µg dose and induced significant anxiety. The average duration of subjective effects increased from 6.7 to 11 h with increasing doses of 25-200 µg. LSD moderately increased blood pressure and heart rate. Ketanserin effectively prevented the response to 200 µg LSD. The LSD dose-response curve showed a ceiling effect for subjective good effects, and ego dissolution and anxiety increased further at a dose above 100 µg. These results may assist with dose finding for future LSD research. The full psychedelic effects of LSD are primarily mediated by serotonin 5-HT<sub>2A</sub> receptor activation.
Biosynthesis of the lysosomal enzyme glucocerebrosidase. (1985)

Multiple biosynthetic forms of glucocerebrosidase were immunoprecipitated after synthesis in vitro using cell-free translation or in vivo using pulse-chase conditions in porcine kidney cells or human fibroblasts. The initial product in vitro was a 52-kDa polypeptide. When canine pancreatic microsomes were present during translation, the nascent polypeptide crossed the microsomal membrane and increased its mass to 60 kDa. Treatment of the 60-kDa polypeptide with endoglycosidase H to remove high mannose carbohydrate yielded a 51-kDa polypeptide. Thus, the membrane-translocated molecule was apparently a high mannose glycoprotein from which a signal peptide had been cleaved, as observed for the lysosomal protease cathepsin D (Erickson, A. H., and Blobel, G. (1979) J. Biol. Chem. 254, 11771-11774). Treatment of pancreatic microsomes or microsomes from porcine kidney cells with protease did not decrease the size of the polypeptide, which shows that this form is not a transmembrane protein bearing a cytoplasmic domain susceptible to digestion. The in vitro product synthesized in the presence of microsomal membranes was indistinguishable from the in vivo product synthesized during pulse-labeling of cultured porcine kidney cells. Following a 2-h chase period, the 60-kDa product was converted to a 59-kDa polypeptide. The major form of glucocerebrosidase detected after a 24-h chase period was a 56-kDa polypeptide, which in turn was converted to a 55-kDa polypeptide by 72 h. The same forms were precipitated from human fibroblasts but the rate of processing was accelerated in this cell type. Limited treatment of the 60-kDa form of glucocerebrosidase with endoglycosidase H suggested that high mannose carbohydrate is added to at least four sites on the polypeptide chain. By 24 h after synthesis, conversion to endoglycosidase H-resistant complex carbohydrate had occurred. Thus, both polypeptide and carbohydrate processing steps are involved in the biosynthesis of glucocerebrosidase.
ChemInform Abstract: Design by Directed Evolution. (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Small lymphocytic lymphoma, marginal zone B-cell lymphoma, and mantle cell lymphoma exhibit distinct gene-expression profiles allowing molecular diagnosis (2003)

Non-germinal center small B-cell lymphomas represent a heterogeneous group of non-Hodgkin lymphomas, the most frequent histologic subtypes being small lymphocytic lymphoma (SLL), splenic marginal zone B-cell lymphoma (MZL), and mantle cell lymphoma (MCL). In order to identify genomic signatures specific for each disease, we analyzed 128 primary tumors using high-density microarrays. Several clusters of genes significantly discriminated the 3 histologic subtypes. Genes associated with cell adhesion, angiogenesis, and inhibition of apoptosis were up-regulated in SLL. Genes associated with intracellular signaling via the AKT1 pathway were up-regulated in splenic MZL. Genes associated with cell cycle control and multidrug resistance were up-regulated in MCL. Using 44 genes selected within the gene clusters discriminant for the 3 lymphoma subtypes, we generated a class prediction score that allowed us to classify the 3 entities in 96% of the cases, including borderline cases. Whereas specific transcriptional profiles easily distinguished all MZL samples, SLL samples, and most of the MCL samples into separate groups, few MCL cases exhibited MZL-type transcriptional profiles. This study demonstrates that SLL, splenic MZL, and MCL possess specific transcriptional profiles that may be relevant to the pathogenesis and the diagnosis of these histologic subtypes.
Folding pathway of the pyridoxal 5′-phosphate C-S lyase MalY from Escherichia coli (2005)

MalY from Escherichia coli is a bifunctional dimeric PLP (pyridoxal 5'-phosphate) enzyme acting as a beta-cystathionase and as a repressor of the maltose system. The spectroscopic and molecular properties of the holoenzyme, in the untreated and NaBH4-treated forms, and of the apoenzyme have been elucidated. A systematic study of the urea-induced unfolding of MalY has been monitored by gel filtration, cross-linking, ANS (8-anilino-1-naphthalenesulphonic acid) binding and by visible, near- and far-UV CD, fluorescence and NMR spectroscopies under equilibrium conditions. Unfolding proceeds in at least three stages. The first transition, occurring between 0 and 1 M urea, gives rise to a partially active dimeric species that binds PLP. The second equilibrium transition involving dimer dissociation, release of PLP and loss of lyase activity leads to the formation of a monomeric equilibrium intermediate. It is a partially unfolded molecule that retains most of the native-state secondary structure, binds significant amounts of ANS (a probe for exposed hydrophobic surfaces) and tends to self-associate. The self-associated aggregates predominate at urea concentrations of 2-4 M for holoMalY. The third step represents the complete unfolding of the enzyme. These results when compared with the urea-induced unfolding profiles of apoMalY and NaBH4-reduced holoenzyme suggest that the coenzyme group attached to the active-site lysine residue increases the stability of the dimeric enzyme. Both holo- and apo-MalY could be successfully refolded into the active enzyme with an 85% yield. Further refolding studies suggest that large misfolded soluble aggregates that cannot be refolded could be responsible for the incomplete re-activation.
Granulocyte Colony-Stimulating Factor Receptor and its Related Receptors (1993)

Click to increase image sizeClick to decrease image sizeKey Words: cell proliferationdifferentiationcytokine receptorreceptor dimerizationsignal transduction
Comparison of the Antimicrobial and Cytotoxic Activities of Twenty Unsaturated Sesquiterpene Dialdehydes from Plants and Mushrooms (1991)

Twenty unsaturated sesquiterpene dialdehydes were tested for antimicrobial, algaecidal, cytotoxic, and mutagenic activity. In addition to the known antifungal activity, polygodial (1) also exhibited antibacterial and cytotoxic activity; epipolygodial (2) was slightly less active. The most active compounds were: isovelleral (7), isoisovelleral (8), velleral (20), and methylmarasmate (6). With the exception of velleral (20), they also exhibited mutagenic activity in the Salmonella/microsome assay. Derivatization to less polar compounds usually increased the antimicrobial and cytotoxic effects and reduced mutagenicity, while the introduction of hydroxyl groups had the reverse effect.
Enzymological Characterization of Recombinant XenopusDG42, A Vertebrate Hyaluronan Synthase (1998)

We have characterized the hyaluronan (HA) synthase activity of the Xenopus DG42 gene product in vitro. The recombinant enzyme produced in yeast does not possess a nascent HA chain and, therefore, is an ideal model system for kinetic studies of the synthase's glycosyltransferase activity. The enzymatic rate was optimal from pH 7.6 to 8.1. Only the authentic sugar nucleotide precursors, UDP-glucuronic acid (UDP-GlcA) and UDP-N-acetylglucosamine (UDP-GlcNAc), were utilized to produce a large molecular weight polymer. UDP-glucose or the galactose epimers of the normal substrates did not substitute. The Michaelis constant, Km, of recombinant DG42 in membranes was 60 +/- 20 and 235 +/- 40 microM for UDP-GlcA and UDP-GlcNAc, respectively, which is comparable to values obtained previously from membranes derived from vertebrate cells. The apparent energy of activation for HA elongation is about 15 kilocalories/mol. DG42 polymerizes HA at average rates of about 80 to 110 monosaccharides/s in vitro. The resulting HA polysaccharide possessed molecular weights spanning 2 x 10(6)-10(7) Da, corresponding to about 10(4) sugar residues. This is the first report characterizing a defined eukaryotic enzyme that can produce a glycosaminoglycan.