gebhart/patrepeval huggingface dataset:
Prediction of enzyme classification from protein sequence without the use of sequence similarity. (1997)

We describe a novel approach for predicting the function of a protein from its amino-acid sequence. Given features that can be computed from the amino-acid sequence in a straightforward fashion (such as pI, molecular weight, and amino-acid composition), the technique allows us to answer questions such as: Is the protein an enzyme? If so, in which Enzyme Commission (EC) class does it belong? Our approach uses machine learning (ML) techniques to induce classifiers that predict the EC class of an enzyme from features extracted from its primary sequence. We report on a variety of experiments in which we explored the use of three different ML techniques in conjunction with training datasets derived from PDB and from Swiss-Prot. We also explored the use of several different feature sets. Our method is able to predict the first EC number of an enzyme with 74% accuracy (thereby assigning the enzyme to one of six broad categories of enzyme function), and to predict the second EC number of an enzyme with 68% accuracy (thereby assigning the enzyme to one of 57 subcategories of enzyme function). This technique could be a valuable complement to sequence-similarity searches and to pathway-analysis methods.
Observing Reusable Password Choices (1992)

From experience, a significant number of recent computer breakins --- perhaps the majority --- can be traced back to an instance of a poorly-chosen reusable password. Once a system intruder has gained access to one account by breaking a password, it is often a simple matter to find system flaws and weaknesses that thereafter allow entry to other accounts and increasing amounts of privilege. The OPUS project being conducted at Purdue is an attempt to screen users&amp;apos; selection of passwords to prevent poor choices. The focus of the project is on using screening methods that are both time and space-efficient and to provide a mechanism that is effective for workstations with little or no disk as well as mainframes. To test this mechanism, we require a representative sample of real passwords. Thus, we constructed a method of sampling real passwords choices as they were made by users. The challenge of such a sampling mechanism is how to protect it from attack, and how to protect the results fro...
Prevalence of Liver Disease and Contributing Factors in Patients Receiving Home Parenteral Nutrition for Permanent Intestinal Failure (2000)

The prevalence of complicated home parenteral nutrition-related liver disease increased with longer duration of parenteral nutrition. This condition was one of the main causes of death in patients with permanent intestinal failure. Parenteral intake of omega-6-rich long-chain triglycerides lipid emulsion consisting of less than 1 g/kg per day is recommended in these patients.
Real-time monitoring of cardiac radio-frequency ablation lesion formation using an optical coherence tomography forward-imaging catheter (2010)

Radio-frequency ablation (rfa) is the standard of care for the treatment of cardiac arrhythmias; however, there are no direct measures of the successful delivery of ablation lesions. Optical coherence tomography (OCT) imaging has the potential to provide real-time monitoring of cardiac rfa therapy, visualizing lesion formation and assessing tissue contact in the presence of blood. A rfa-compatible forward-imaging conical scanning probe is prototyped to meet this need. The forward-imaging probe provides circular scanning, with a 2-mm scan diameter and 30-µm spot size. During the application of rf energy, dynamics are recorded at 20 frames per second with a 40-kHz A-line rate. Real-time monitoring of cardiac rfa lesion formation and imaging in the presence of blood is demonstrated ex vivo in a swine left ventricle with a forward, flexible, circular scanning OCT catheter.
The Practice of Optimal Execution (2006)

Optimal execution is a term that is widely used, and even though the concept is intuitively clear, in practice it is not uniformly achieved. In fact, the gap between this intuition and the perceived reality of algorithm behavior probably accounts for much of the remaining skepticism regarding algorithmic trading. This article examines why the gap exists and how it can be reduced. The typical approach is based upon a formulation that abstracts away from critical elements of the problem facing a trader who is executing in actual markets. It is not surprising that this approach fails to address a number of material risks facing the trader and portfolio manager. One particular risk is known as signaling risk, the risk of conveying information about trading intentions to market participants. It is demonstrated that when signaling risk is ignored, the typical solution is not the strategy that an intelligent, risk-averse rational trader would employ in real-time. By examining how information is utilized by the market, it is possible to derive practical conclusions that can help manage signaling risk from within a trading algorithm. Building on this, it is shown how the execution optimization problem should be revised to provide a better representation of actual trading environments. Solutions to the revised problem correspond to optimal trading strategies that can be employed in practice with greater confidence that signaling risk is being managed.
UV‐B RADIATION EFFECTS ON PHOTOSYNTHESIS, GROWTH and CANNABINOID PRODUCTION OF TWO Cannabis sativa CHEMOTYPES (1987)

Abstract The effects of UV‐B radiation on photosynthesis, growth and cannabinoid production of two greenhouse‐grown C. sativa chemotypes (drug and fiber) were assessed. Terminal meristems of vegetative and reproductive tissues were irradiated for 40 days at a daily dose of 0, 6.7 or 13.4 kJ m ‐2 biologically effective UV‐B radiation. Infrared gas analysis was used to measure the physiological response of mature leaves, whereas gas‐liquid chromatography was used to determine the concentration of cannabinoids in leaf and floral tissue. There were no significant physiological or morphological differences among UV‐B treatments in either drug‐ or fiber‐type plants. The concentration of Δ 9 ‐tetrahydrocannabinol (Δ 9 ‐THC), but not of other cannabinoids, in both leaf and floral tissues increased with UV‐B dose in drug‐type plants. None of the cannabinoids in fiber‐type plants were affected by UV‐B radiation. The increased levels of Δ 9 ‐THC in leaves after irradiation may account for the physiological and morphological tolerance to UV‐B radiation in the drug‐type plants. However, fiber plants showed no comparable change in the level of cannabidiol (a cannabinoid with UV‐B absorptive characteristics similar to Δ 9 THC). Thus the contribution of cannabinoids as selective UV‐B filters in C. sativa is equivocal.
Short-Term Metabolic Effects of Recombinant Human Insulin-like Growth Factor I in Healthy Adults (1987)

Insulin-like growth factor I (IGF I) is structurally similar to insulin and shares many of its biologic properties. We compared the short-term metabolic effects of recombinant IGF I (100 micrograms [13.3 nmol] per kilogram of body weight) and insulin (0.15 IU [1 nmol] per kilogram) in eight healthy volunteers (four men and four women). The hypoglycemic responses to both hormones were nearly identical in the doses used. The lowest blood glucose levels were reached after 30 minutes: 1.98 +/- 0.44 mmol per liter after IGF I and 1.78 +/- 0.29 after insulin. On a molar basis, IGF I was only 6 percent as potent as insulin in the production of hypoglycemia. Insulin also inhibited lipolysis more effectively than IGF I. Levels of epinephrine, norepinephrine, growth hormone, glucagon, and cortisol responded similarly to both agents. The hypoglycemia produced by IGF I is probably due to the supraphysiologic concentrations of the free peptide that result from its rapid intravenous injection. Fifteen minutes after injection, the serum level of IGF I increased from 144 +/- 38 ng per milliliter at base line to 424 +/- 56, of which 80 percent was free in the plasma (not bound to IGF carrier proteins). The determination of whether any of the short-term metabolic effects of IGF I have any clinical application will require further investigation.
Block copolymers: synthetic strategies, physical properties, and applications (2003)

Preface. Abbreviations and Symbols. I: BLOCK COPOLYMER SYNTHESIS. 1 Block Copolymers by Anionic Polymerization. 2 Block Copolymers by Cationic Polymerization. 3 Block Copolymers by Living Free Radical Polymerization. 4 Block Copolymers by Group Transfer Polymerization. 5 Block Copolymers by Ring Opening Metathesis Polymerization. 6 Synthesis of Block Copolymers by a Combination of Different Polymerization Methods. 7 Synthesis of Block Copolymers by Chemical Modification. 8 Nonlinear Block Copolymers. II: MOLECULAR CHARACTERIZATION OF BLOCK COPOLYMERS. 9 Molecular Characterization of Block Copolymers. III: SOLUTION PROPERTIES OF BLOCK COPOLYMERS. 10 Dilute Solutions of Block Copolymers in Nonselective Solvents. 11 Dilute Solutions of Block Copolymers in Selective Solvents. 12 Adsorption of Block Copolymers At Solid-Liquid Interfaces. IV: PHYSICAL PROPERTIES OF BLOCK COPOLYMERS. 13 Theory. 14 Structure Factor and Chain Architecture. 15 Block Copolymer Phase State. 16 Viscoelastic Properties of Block Copolymers. 17 Phase Transformation Kinetics. 18 Block Copolymers with Strongly Interacting Groups. 19 Block Copolymer Morphology. 20 Block Copolymer Dynamics. V: APPLICATIONS. 21 Block Copolymer Applications. Index.
Regulatory T cells: balancing protection versus pathology (2016)

Foxp3+ regulatory T cells (Tregs) maintain immune tolerance, prevent autoimmunity and modulate immune responses during infection and cancer. Recent studies have revealed considerable heterogeneity and plasticity within the Treg compartment, depending on the immunological context, which may result in Tregs losing their suppressive function in inflammatory environments. We review how dysfunctional Tregs contribute to disease pathogenesis in inflammatory conditions and how inappropriate regulatory responses may hamper protective immunity in the context of infection and cancer. We also discuss how Tregs might be targeted therapeutically to re-establish a proper balance between regulatory and effector responses in autoimmunity, infections, and cancer.
THE REDUCING ACTION OF THE GRIGNARD REAGENT AND THE SYNTHESIS OF TERTIARY ALIPHATIC CARBINOLS (1932)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTHE REDUCING ACTION OF THE GRIGNARD REAGENT AND THE SYNTHESIS OF TERTIARY ALIPHATIC CARBINOLSA. H. Blatt and Julius F. Stone Jr.Cite this: J. Am. Chem. Soc. 1932, 54, 4, 1495–1499Publication Date (Print):April 1, 1932Publication History Published online1 May 2002Published inissue 1 April 1932https://pubs.acs.org/doi/10.1021/ja01343a034https://doi.org/10.1021/ja01343a034research-articleACS PublicationsRequest reuse permissionsArticle Views68Altmetric-Citations5LEARN 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
Hemocompatibility on graft copolymers composed of poly(2‐methacryloyloxyethyl phosphorylcholine) side chain and poly(n‐butyl methacrylate) backbone (1994)

To improve the hemocompatibility on hydrophobic biomedical materials by a simple coating technique, graft copolymers composed of a hydrophilic side chain with phospholipid polar groups and a hydrophobic backbone were synthesized. The hydrophilic chain had phospholipid polar groups, poly[2-methacryloyloxyethyl phosphorylcholine (MPC)], and the hydrophobic backbone was poly[n-butyl methacrylate (BMA)]. Because the graft copolymers obtained could dissolve in ethanol, they could be used as a coating material. When the poly(MPC-graft-BMA) was coated onto a poly(BMA) membrane, the composition of the MPC units on the surface was maintained in the bulk graft copolymer even after immersion in water. Protein adsorption on the membrane coated with the graft copolymer from human plasma detected by a gold-colloid labeled immunoassay was drastically decreased compared with that on glass and the original membrane. Moreover, blood cell adhesion, activation, and aggregation on the membrane after contact with human citrated whole blood were suppressed by the coating of the graft copolymer. These results clearly show that the poly(MPC-graft-BMA) is a suitable material for improving hemocompatibility on the biomedical devices because of its protein adsorption and cell adhesion resistant properties.
High Sensitivity Methods to Quantify Chloroquine and its Metabolite in Human Blood Samples Using LC–MS/MS (2019)

The developed methods demonstrated satisfactory validation performance with high sensitivity and selectivity. The assays used simple and easy to automate extraction techniques. All methods were reliable with robust performance and demonstrated to be suitable to implement into high-throughput routine analysis of clinical pharmacokinetic samples.
Discovery of Cathepsin S Inhibitor LY3000328 for the Treatment of Abdominal Aortic Aneurysm (2014)

Cathepsin S (Cat S) plays an important role in many pathological conditions, including abdominal aortic aneurysm (AAA). Inhibition of Cat S may provide a new treatment for AAA. To date, several classes of Cat S inhibitors have been reported, many of which form covalent interactions with the active site Cys25. Herein, we report the discovery of a novel series of noncovalent inhibitors of Cat S through a medium-throughput focused cassette screen and the optimization of the resulting hits. Structure-based optimization efforts led to Cat S inhibitors such as 5 and 9 with greatly improved potency and drug disposition properties. This series of compounds binds to the S2 and S3 subsites without interacting with the active site Cys25. On the basis of in vitro potency, selectivity, and efficacy in a CaCl2-induced AAA in vivo model, 5 (LY3000328) was selected for clinical development.
Overexpression of a zinc-finger protein gene from rice confers tolerance to cold, dehydration, and salt stress in transgenic tobacco (2004)

Stress perception and signal transduction leading to tolerance involve a complex interplay of different gene products. We describe here the isolation and characterization of an intronless gene (OSISAP1) from rice encoding a zinc-finger protein that is induced after different types of stresses, namely cold, desiccation, salt, submergence, and heavy metals as well as injury. The gene is also induced by stress hormone abscisic acid. Overexpression of the gene in transgenic tobacco conferred tolerance to cold, dehydration, and salt stress at the seed-germination/seedling stage as reflected by the percentage of germination/green seedlings, the fresh weight of seedlings, and their developmental pattern. Thus, OSISAP1 seems to be an important determinant of stress response in plants.
A constant rate of spontaneous mutation in DNA-based microbes. (1991)

In terms of evolution and fitness, the most significant spontaneous mutation rate is likely to be that for the entire genome (or its nonfrivolous fraction). Information is now available to calculate this rate for several DNA-based haploid microbes, including bacteriophages with single- or double-stranded DNA, a bacterium, a yeast, and a filamentous fungus. Their genome sizes vary by approximately 6500-fold. Their average mutation rates per base pair vary by approximately 16,000-fold, whereas their mutation rates per genome vary by only approximately 2.5-fold, apparently randomly, around a mean value of 0.0033 per DNA replication. The average mutation rate per base pair is inversely proportional to genome size. Therefore, a nearly invariant microbial mutation rate appears to have evolved. Because this rate is uniform in such diverse organisms, it is likely to be determined by deep general forces, perhaps by a balance between the usually deleterious effects of mutation and the physiological costs of further reducing mutation rates.
Inhibitors of the entry of HIV into host cells. (2003)

The development of mechanistic insight into the process by which HIV enters host cells has revealed a panoply of targets that offer considerable potential as sites for pharmacological intervention. The gp120/gp41 protein complex, expressed on the virion surface, mediates HIV entry by a process initiated by the engagement of the host cell receptor CD4. Subtle conformational changes triggered by this interaction expose elements of gp120 to the seven-transmembrane, G protein-coupled chemokine receptors CCR5 or CXCR4 expressed on host cells, a contact that relieves constraints imposed on gp41 by gp120. This leads to a major conformational rearrangement of gp41, which results in the insertion of the fusion peptide into the host cell membrane and the assembly of the amino terminus heptad repeat into a trimeric form that is subsequently recognized by the carboxy terminal heptad repeat. The latter process leads to juxtaposition of the viral and host cell membranes, a prelude to fusion. The most prominent strategies and targets that are actively being exploited as drug discovery opportunities are inhibition of the attachment of HIV to host cells, blockade of chemokine receptors and interference with the function of gp41. Inhibitors of each of these steps in the HIV entry process with potential clinical relevance are reviewed in the context of their status in the drug development process. The most significant entity to emerge from this area of research to date is enfuvirtide, a 36-amino acid derivative that interferes with the function of gp41. Enfuvirtide is the first HIV entry inhibitor to be granted a license for marketing (it was approved in the US and Europe in March 2003), and its introduction portends the beginning of what promises to be an exciting new era of HIV therapy.
Normobaric hyperoxia inhibits NADPH oxidase‐mediated matrix metalloproteinase‐9 induction in cerebral microvessels in experimental stroke (2008)

Matrix metalloproteinase-9 (MMP-9) and NADPH oxidase contribute to blood-brain barrier (BBB) disruption after ischemic stroke. We have previously shown that normobaric hyperoxia (NBO) treatment reduces MMP-9 and oxygen free radical generation in ischemic brain. In this study, we tested the hypothesis that NBO protects the BBB through inhibiting NADPH oxidase-mediated MMP-9 induction in transient focal cerebral ischemia. Male Sprague-Dawley rats (n = 69) were given NBO (95% O2) or normoxia (21% O2) during 90-min filament occlusion of the middle cerebral artery. Cerebral microvessels were isolated for analyzing MMP-9 and NADPH oxidase. BBB damage was non-invasively quantified with magnetic resonance imaging. In normoxic rats, both NADPH oxidase catalytic subunit gp91(phox) and MMP-9 expression were up-regulated in ischemic hemispheric microvessels after 90-min middle cerebral artery occlusion with 22.5 h reperfusion. Inhibition of NADPH oxidase with apocynin reduced the MMP-9 increase, indicating a causal link between NADPH oxidase-derived superoxide and MMP-9 induction. NBO treatment inhibited gp91(phox) expression, NADPH oxidase activity, and MMP-9 induction, which led to significantly less BBB damage and brain edema in the ischemic brain. These results suggest that gp91(phox) containing NADPH oxidase plays an important role in MMP-9 induction in ischemic BBB microvasculature, and that NBO treatment may attenuate MMP-9 induction and brain edema through inhibiting NADPH oxidase after transient cerebral ischemia.
Mechanisms of Phrenic Nerve Injury During Radiofrequency Ablation at the Pulmonary Vein Orifice (2005)

Phrenic nerve injury can be more common than anticipated with RF ablation at the RSPV orifice. Relatively low tissue temperatures can injure the nerve. Immediate nerve effects suggest a second mechanism of nerve dysfunction related to electrical current. Transient nerve effects occur prior to permanent damage, providing an opportunity to discontinue energy delivery before permanent injury.
Chaperonins groEL and groES promote assembly of heterotetramers (alpha 2 beta 2) of mammalian mitochondrial branched-chain alpha-keto acid decarboxylase in Escherichia coli. (1992)

We have investigated the possible role of chaperonins groEL and groES in the folding and assembly of heterotetramers (alpha 2 beta 2) of mammalian mitochondrial branched-chain alpha-keto acid decarboxylase (E1) in Escherichia coli. The mature E1 alpha subunit fused to maltose-binding protein (MBP) was coexpressed with mature E1 beta on the same vector in ES- and EL- mutant strains. Only small or trace amounts of active E1 component were obtained. Cotransformation of the ES- mutant host with a second vector overexpressing groEL and groES resulted in a greater than 500-fold increase in E1-specific activity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed that the content of both MBP-E1 alpha and E1 beta polypeptides was markedly increased in the presence of overexpressed chaperonin proteins. The time course studies showed that the increase in E1-specific activity and subunit levels correlated with the increase in groEL and groES until the concentration of the chaperonins reached a saturating level in the cell. The functional MBP-E1 fusion protein from ES- double transformants were purified by amylose resin affinity chromatography. The MBP moiety was removed by subsequent digestion with Factor Xa endoprotease, followed by Sephacryl S-300HR chromatography. It was found that E1 alpha and E1 beta assembled into an active 160-kDa species, which was consistent with the alpha 2 beta 2 structure of E1. The present results demonstrate that chaperonins groEL and groES promote folding and assembly of heterotetrameric proteins of mammalian mitochondrial origin.
RNA-protein interactions in regulation of picornavirus RNA translation (1996)

The translation of picornavirus RNA occurs by a cap-independent mechanism directed by a region of about 450 nucleotides from the 5' untranslated region, termed an internal ribosome entry site (IRES). Internal initiation of protein synthesis occurs without any requirement for viral proteins. Furthermore, it is maintained when host cell protein synthesis is almost abolished. By using in vitro translation systems, two distinct families of IRES elements which have very different predicted RNA secondary structures have been defined. The cardiovirus and aphthovirus elements function very efficiently in rabbit reticulocyte lysate, whereas the enterovirus and rhinovirus elements function poorly in this system. However, supplementation of this translation system with additional cellular proteins can stimulate translation directed by the enterovirus and rhinovirus RNAs and reduce production of aberrant initiation products. The characterization of cellular proteins interacting with the picornavirus IRES is a major focus of research. Many different protein species can be observed to interact with regions of the IRES by in vitro analyses, e.g., UV cross-linking. However, the function and significance of many of these interactions are not always known. For two proteins, La and the polypyrimidine tract-binding protein, evidence has been obtained for a functional role of their interaction with IRES elements.