gebhart/patrepeval huggingface dataset:
A synthetic substrate assay for the gamma‐secretase of the β‐A4 amyloid of alzheimer's disease (1995)

gamma-secretase, the endoprotease which releases the C-terminus of beta A4 amyloid peptide, cleaves within the hydrophobic transmembrane domain of the amyloid precursor protein. In order to obtain a substrate for gamma-secretase, a dodecapeptide which spans the cleavage site was synthesized, labelled with 125-iodine and conjugated to an agarose gel. A radiometric solid-phase assay was developed using this immobilized substrate. Peptide products were separated by reverse-phase HPLC and TLC to allow characterization of the cleavage site(s).
A model for intent interpretation for multiple agents with conflicts (2002)

Intent interpretation is the process of forming a causal explanation of the observed actions of an agent in terms of the current purposes of the agent. Most of the current work in this area has dealt with interpretation of the actions of single agents without unresolved conflicts. This paper describes the use of the plan-goal representational approach as originally formulated in Geddes (1989) to interpret actions of multiple agents with unresolved conflicts. This situation is of importance in the practical world, arising often in cooperative team and organizational behavior as well as in overt adversarial behavior.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
PILER-CR: Fast and accurate identification of CRISPR repeats (2007)

PILER-CR is a useful tool for rapid identification and classification of CRISPR repeats. The software is donated to the public domain. Source code and a Linux binary are freely available at http://www.drive5.com/pilercr.
Identification of interdomain sequences promoting the intronless evolution of a bacterial protein family. (1996)

In the evolution of eukaryotic genes, introns are believed to have played a major role in increasing the probability of favorable duplication events, chance recombinations, and exon shuffling resulting in functional hybrid proteins. As a rule, prokaryotic genes lack introns, and the examples of prokaryotic introns described do not seem to have contributed to gene evolution by exon shuffling. Still, certain protein families in modern bacteria evolve rapidly by recombination of genes, duplication of functional domains, and as shown for protein PAB of the anaerobic bacterial species Peptostreptococcus magnus, by the shuffling of an albumin-binding protein module from group C and G streptococci. Characterization of a protein PAB-related gene in a P. magnus strain with less albumin-binding activity revealed that the shuffled module was missing. Based on this fact and observations made when comparing gene sequences of this family of bacterial surface proteins interacting with albumin and/or immunoglobulin, a model is presented that can explain how this rapid intronless evolution takes place. A new kind of genetic element is introduced: the recer sequence promoting interdomain, in frame recombination and acting as a structure-less flexibility-promoting spacer in the corresponding protein. The data presented also suggest that antibiotics could represent the selective pressure behind the shuffling of protein modules in P. magnus, a member of the indigenous bacterial flora.
An oncogenic form of p53 confers a dominant, gain-of-function phenotype that disrupts spindle checkpoint control (1998)

Although it is well-established that p53 functions as a tumor suppressor gene, certain mutations exhibit gain-of-function activities that increase oncogenic transformation. We have found a common class of p53 missense mutation that exhibits a dominant, gain-of-function activity that generates genomic instability. Fibroblasts from Li-Fraumeni syndrome heterozygotes with such mutations generate polyploid cells when exposed to spindle depolymerizing agents. Expression of such mutant alleles in normal fibroblasts yields the same phenotype. This class of dominant, gain-of-function p53 mutation (p53(RSC), relaxed spindle checkpoint allele) does not require the transcriptional activation function of p53 for this behavior. Thus p53 mutations can contribute to progression of a cancer cell not only by absence of p53 tumor suppressor activity but also by the presence of an activity that promotes genetic instability.
Impact of an ectoparasite on the immunity and pathology of an invertebrate: Evidence for host immunosuppression and viral amplification (2005)

Varroa mites (Varroa destructor) are ectoparasites of honey bees (Apis mellifera) and cause serious damage to bee colonies. The mechanism of how varroa mites kill honey bees remains unclear. We have addressed the effects of the mites on bee immunity and the replication of a picorna-like virus, the deformed wing virus (DWV). The expression of genes encoding three antimicrobial peptides (abaecin, defensin, and hymenoptaecin) and four immunity-related enzymes (phenol oxidase, glucose dehydrogenase, glucose oxidase, and lysozyme) were used as markers to measure the difference in the immune response. We have demonstrated an example of an ectoparasite immunosuppressing its invertebrate host with the evidence that parasitization significantly suppressed expression of these immunity-related genes. Given that ticks immunosuppress their vertebrate hosts, our finding indicates that immunosuppression of hosts may be a common phenomenon in the interaction and coevolution between ectoparasites and their vertebrate and invertebrate hosts. DWV viral titers were significantly negatively correlated with the expression levels of the immunity-related enzymes. All bees had detectable DWV. Mite-infested pupae developed into adults with either normal or deformed wings. All of the deformed-wing bees were greatly infected by DWV (approximately 10(6) times higher than varroa-infested but normal-winged bees). Injection with heat-killed bacteria dramatically promoted DWV titers (10(5) times in 10 h) in the mite-infested, normal-winged bees to levels similar to those found in mite-infested, deformed-wing bees. Varroa mites may cause the serious demise of honey bees by suppressing bee immunity and by boosting the amplification of DWV in bees exposed to microbes.
Intestinal Epithelial Cell Surface Membrane Glycoprotein Synthesis (1973)

Abstract Cell surface glycoproteins, which have been implicated in the control and expression of cell turnover, differentiation, and malignant transformation in tissue culture studies, were examined for a possible similar role in the intestinal epithelial cell. This cell is characterized by a rapid cell turnover and by a gradient of differentiation from crypt to villus. A method was developed which isolated epithelial cells from different levels of crypt and villus areas and when radioactive labeled d-glucosamine, l-fucose, or d-galactosamine were given intraperitoneally into a rat, a sharp gradient of radioactive incorporation paralleled the specific activity gradients of sucrase and alkaline phosphatase. Isolated epithelial cells incubated with d-[1-14C]glucosamine also showed that the upper villus cells had a much higher incorporation of d-[1-14C]glucosamine than did crypt cells. Subcellular fractionation of the intestinal cells labeled in vivo demonstrated that the highest specific activity was in the purified microvillus plasma membranes and the lowest specific activity was in the microsomal and cytosol fractions. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of microvillus membranes showed peaks of d-[1-14C]glucosamine incorporation which coincided with peaks of sucrase and alkaline phosphatase activities and most of the bands which stained for protein also stained for glycoprotein. Microvillus core proteins separated on sodium dodecyl sulfate polyacrylamide did not show peaks of d-[1-14C]glucosamine incorporation and did not stain for glycoprotein. These results suggest that the more differentiated upper villus cells incorporate more labeled sugar precursors into membrane glycoproteins than the less differentiated lower villus or crypt cells and that these membrane glycoproteins are associated with membrane-bound enzymes.
Genome-Wide Analysis of Core Cell Cycle Genes in Arabidopsis (2002)

Cyclin-dependent kinases and cyclins regulate with the help of different interacting proteins the progression through the eukaryotic cell cycle. A high-quality, homology-based annotation protocol was applied to determine the core cell cycle genes in the recently completed Arabidopsis genome sequence. In total, 61 genes were identified belonging to seven selected families of cell cycle regulators, for which 30 are new or corrections of the existing annotation. A new class of putative cell cycle regulators was found that probably are competitors of E2F/DP transcription factors, which mediate the G1-to-S progression. In addition, the existing nomenclature for cell cycle genes of Arabidopsis was updated, and the physical positions of all genes were compared with segmentally duplicated blocks in the genome, showing that 22 core cell cycle genes emerged through block duplications. This genome-wide analysis illustrates the complexity of the plant cell cycle machinery and provides a tool for elucidating the function of new family members in the future.
Small-Molecule Interferon Inducers. Toward the Comprehension of the Molecular Determinants through Ligand-Based Approaches (2009)

Hepatitis C is becoming an increasingly common cause of mortality especially in the HIV-coinfected group. Due to the efficacy of interferon (IFN) based therapy in the treatment of hepatitis C, various compounds possessing IFN-inducing activity have been hitherto reported. In the present study, we describe how steric, electrostatic, hydrophobic, and hydrogen-bonding interactions might influence the biological activity of a published set of IFN inducers, using a three-dimensional quantitative structure-activity relationship (3-D QSAR) approach. Analyses were conducted evaluating different series of compounds structurally related to 8-hydroxyadenines and 1H-imidazo[4,5-c]quinolines. A ligand-based alignment protocol in combination with the GRID/GOLPE approach was applied: 62 3-D QSAR models were derived using different GRID probes and several training sets. Performed 3-D QSAR investigations proved to be of good statistical value displaying r2, q2CV-LOO, and cross-validated SDEP values of 0.73, 0.61, 0.61 and 0.89, 0.64, 0.58 using the OH or the DRY probe, respectively. Additionally, the predictive performance was evaluated using an external test set of 20 compounds. Analyses of the resulting models led to the definition of a pharmacophore model that can be of interest to explain the observed affinities of known compounds as well as to design novel low molecular weight IFN inducers (IFNIs). To the best of our knowledge, this is the first 3-D QSAR application on IFN-inducing agents.
A Selectiveα-L-Fucosidase Inhibitor Based on an Aminocyclopentane Framework (1999)

(1R,2R,3R,4S,5R)-4-amino-5-methylcyclopentane-1,2,3-triol (1) was prepared stereoselectively from D-ribose (Scheme). Aminocyclopentanetriol 1, which by its design may be considered an analog of the fucosyl cation, inhibits α-L-fucosidase selectively (Ki=28 μM) over α- and β-glucosidase, α- and β-mannosidase, and α- and β-galactosidase (Table).
Photopatterning and selective electroless metallization of surface-attached ligands (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotopatterning and selective electroless metallization of surface-attached ligandsWalter J. Dressick, Charles S. Dulcey, Jacque H. Georger, Jr., and Jeffrey M. CalvertCite this: Chem. Mater. 1993, 5, 2, 148–150Publication Date (Print):February 1, 1993Publication History Published online1 May 2002Published inissue 1 February 1993https://pubs.acs.org/doi/10.1021/cm00026a002https://doi.org/10.1021/cm00026a002research-articleACS PublicationsRequest reuse permissionsArticle Views262Altmetric-Citations100LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Bimodal protein solubility distribution revealed by an aggregation analysis of the entire ensemble of Escherichia coli proteins (2009)

Protein folding often competes with intermolecular aggregation, which in most cases irreversibly impairs protein function, as exemplified by the formation of inclusion bodies. Although it has been empirically determined that some proteins tend to aggregate, the relationship between the protein aggregation propensities and the primary sequences remains poorly understood. Here, we individually synthesized the entire ensemble of Escherichia coli proteins by using an in vitro reconstituted translation system and analyzed the aggregation propensities. Because the reconstituted translation system is chaperone-free, we could evaluate the inherent aggregation propensities of thousands of proteins in a translation-coupled manner. A histogram of the solubilities, based on data from 3,173 translated proteins, revealed a clear bimodal distribution, indicating that the aggregation propensities are not evenly distributed across a continuum. Instead, the proteins can be categorized into 2 groups, soluble and aggregation-prone proteins. The aggregation propensity is most prominently correlated with the structural classification of proteins, implying that the prediction of aggregation propensity requires structural information about the protein.
Use of Current Generation Perfluorocarbon Emulsions in Cardiac Surgery (1994)

The development of novel perfluorocarbon emulsions that contain higher concentrations of perfluorochemicals than previous emulsions has renewed interest in the use of this class of erythrocyte substitute in cardiopulmonary bypass (CPB). Perfluorocarbons have the potential to increase the oxygen content of the perfusate and thus increase the capacity of the heart-lung machine to deliver oxygen to the body during CPB. Increasing the capacity of the heart-lung machine to deliver oxygen to the body has important implications for the conduct of cardiac operations. For example, adding perfluorocarbons to the pump prime solution may allow larger volumes of blood to be withdrawn from the patient immediately prior to bypass for transfusion after bypass. Lowering the acceptable hematocrit during CPB with the use of perfluorocarbons may also decrease the need for homologous transfusions of erythrocytes in neonates or anemic adults who undergo CPB.
Predominance of Th1 immune response in diffuse proliferative lupus nephritis (2001)

We have identified a predominance of Thl-type response in both peripheral and renal tissues of patients with DPLN, suggesting that the peripheral blood Thl:Th2 ratio directly reflects the local histopathologic findings. In patients with lupus nephritis, the peripheral blood Th1:Th2 ratio could be useful as a parameter that reflects the renal histologic activity or the strength of the local Thl response.
Pulse oximetry through spectral analysis (2002)

Signal processing algorithms for pulse oximetry waveforms are typically completed in the time domain utilizing analog filtering and moving average techniques. This investigation evaluated the use of spectral analysis as an alternative algorithm for the signal processing of pulse oximetry waveforms. Fast Fourier transformation of eight separate red and infrared waveform data segments was accomplished via a custom C-program. Magnitudes of spectral peaks in the cardiac spectrum were utilized to compute an SpO2 value. In this limited trial, spectral analysis derived SpO2 values were at least as accurate as time series SpO2 values. However, further investigation is needed to further define the limits of spectral analysis on pulse oximetry waveforms with unusual respiratory variations, electrical noise, and motion artifact.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mesalazine inhibits activation of transcription factor NF-κB in inflamed mucosa of patients with ulcerative colitis (2000)

OBJECTIVES: The salicylate mesalazine is commonly used for the treatment of inflammatory bowel diseases, yet its precise mechanism of action is unknown. Because transcription factor NF-κB plays an important role in inflammatory bowel diseases, we investigated the effects of mesalazine therapy on NF-κB activation in patients with ulcerative colitis. METHODS: A total of 20 patients with moderately active ulcerative colitis received mesalazine for 8 wk. Biopsies were taken before and after drug administration and analyzed for NF-κB activation using an antibody specific for active NF-κB. RESULTS: In biopsies of active ulcerative colitis but not in noninflamed mucosa, activation of NF-κB was detected predominantly in macrophages. Mesalazine therapy resulted in a strong abrogation of NF-κB activation in situ. CONCLUSIONS: Our results suggest that the therapeutic properties of mesalazine rely at least in part on the inhibition of NF-κB activation, resulting in the suppression of proinflammatory gene expression in the inflamed mucosa.
Field emission of carbon nanotubes grown on carbon cloth (2004)

Field emission from carbon nanotubes grown on carbon cloth has been studied. An extremely low electric field of less than 0.4V∕μm is required to reach an emission current density of 1mA∕cm2. This ultralow operating electric field of carbon nanotubes grown on carbon cloth is mainly due to a very high field enhancement factor of 1.882×104, which is the result of geometrical configuration of the carbon nanotubes and the substrate. In addition to the field enhancement, the highly disordered microstructure of carbon nanotubes grown on carbon cloth plays an important role to field emission. This unexpected result indicates that the roughness of the substrates on which carbon nanotubes grow is very important. This result also brings us significantly closer to practical applications such as highly efficient lamps, field emission displays, micro vacuum electron sources, etc.
The Use of Liver Transglutaminase for Protein Labeling (1977)

Guinea‐pig transglutaminase catalyzes the formation of an amide bond between the γ‐carboxyl group of peptide‐bound glutamine and a variety of amines, including fluorescent or spin‐labeled derivatives. A systematic study was conducted with this enzyme in order to establish its usefulness as a protein‐labeling technique. Transglutaminase‐catalyzed amine incorporation was tested with isolated proteins, intact cells, membrane preparations, and virus particles. It was found that, due to its large molecular weight and its specificity, the transglutaminase reaction is limited to highly exposed glutamine residues. For example, proteins such as tubulin and α 2 ‐macroglobulin were modified while immunoglobulins (IgG) from a variety of sources were not, despite their high glutamine content. The peptide hormone glucagon was modified by transglutaminase, which resulted in the loss of hormonal activity. Most of the intact cells were not labeled with transglutaminase. Only in the case of human fibroblasts the labeling of a few heavy‐molecular‐weight proteins, including large external transformation‐sensitive (LETS) protein, occurred. However, isolated membrane preparations, such as erythrocyte ghosts, sarcoplamic reticulum and retinal disc membranes, were significantly labeled. Intact influenza virions were susceptible to the transglutaminase‐catalyzed reaction; however, only hemaglutinin but not neuraminidase was labeled. The transglutaminase reaction was found useful when specific and limited labeling is required. This technique should be particularly amenable for the introduction of fluorescent probes into membrane proteins and for elucidation of the structure‐function relationship of the proteins.
A Role for the Mouse 12/15-Lipoxygenase Pathway in Promoting Epithelial Wound Healing and Host Defense (2005)

The surface of the eye actively suppresses inflammation while maintaining a remarkable capacity for epithelial wound repair. Our understanding of mechanisms that balance inflammatory/reparative responses to provide effective host defense while preserving tissue function is limited, in particular, in the cornea. Lipoxin A(4) (LXA(4)) and docosahexaenoic acid-derived neuroprotectin D1 (NPD1) are lipid autacoids formed by 12/15-lipoxygenase (LOX) pathways that exhibit anti-inflammatory and neuroprotective properties. Here, we demonstrate that mouse corneas generate endogenous LXA(4) and NPD1. 12/15-LOX (Alox15) and LXA(4) receptor mRNA expression as well as LXA(4) formation were abrogated by epithelial removal and restored during wound healing. Amplification of these pathways by topical treatment with LXA(4) or NPD1 (1 microg) increased the rate of re-epithelialization (65-90%, n = 6-10, p < 0.03) and attenuated the sequelae of thermal injury. In contrast, the proinflammatory eicosanoids, LTB(4) and 12R-hydroxyeicosatrienoic acid, had no impact on corneal re-epithelialization. Epithelial removal induced a temporally defined influx of neutrophils into the stroma as well as formation of the proinflammatory chemokine KC. Topical treatment with LXA(4) and NPD1 significantly increased PMNs in the cornea while abrogating KC formation by 60%. More importantly, Alox15-deficient mice exhibited a defect in both corneal re-epithelialization and neutrophil recruitment that correlated with a 43% reduction in endogenous LXA(4) formation. Collectively, these results identify a novel action for the mouse 12/15-LOX (Alox15) and its products, LXA(4) and NPD1, in wound healing that is distinct from their well established anti-inflammatory properties.
Improvements in Respiratory and Psychosocial Functioning following Total Laryngectomy by the Use of a Heat and Moisture Exchanger (1993)

A prospective clinical study in 61 patients was undertaken to investigate the subjective and objective influence of a heat and moisture exchanger (HME) on the respiratory and psychosocial problems following total laryngectomy. Although statistical comparisons failed to detect significant differences between the experimental and the control groups, there was a clear trend toward improvements in respiratory and psychosocial functioning in the experimental group. Analyses of differences over time within the HME user group showed significant reductions in the incidence of coughing, the mean daily frequency of sputum production, forced expectoration, and stoma cleaning. Significant improvements were also found in shortness of breath, fatigue and malaise, sleep problems, levels of anxiety and depression, and perceived voice quality. Pulmonary function tests showed significant improvements in inspiratory flow and volume values following use of the HME. This objective improvement in inspiratory pulmonary function reflects the decrease in sputum production reported by the patients.