gebhart/patrepeval huggingface dataset:
HEAT CAPACITY IN PROTEINS (2005)

Heat capacity (Cp) is one of several major thermodynamic quantities commonly measured in proteins. With more than half a dozen definitions, it is the hardest of these quantities to understand in physical terms, but the richest in insight. There are many ramifications of observed Cp changes: The sign distinguishes apolar from polar solvation. It imparts a temperature (T) dependence to entropy and enthalpy that may change their signs and which of them dominate. Protein unfolding usually has a positive deltaCp, producing a maximum in stability and sometimes cold denaturation. There are two heat capacity contributions, from hydration and protein-protein interactions; which dominates in folding and binding is an open question. Theoretical work to date has dealt mostly with the hydration term and can account, at least semiquantitatively, for the major Cp-related features: the positive and negative Cp of hydration for apolar and polar groups, respectively; the convergence of apolar group hydration entropy at T approximately 112 degrees C; the decrease in apolar hydration Cp with increasing T; and the T-maximum in protein stability and cold denaturation.
Small molecules originating from microbes (SMOM) and their role in microbes–host relationship (2000)

A hypothesis proposed, according to which non-specific purulent-inflammatory processes are mainly caused by disturbances at low-molecular level—i.e. by small molecules originating from microbes (SMOM), while SMOM homeostasis decompensation takes the leading role in complex polyfactorial pathogenesis of sepsis. The hypothesis is logically justified by understanding the reasonableness for creation within the ontogenesis the system of signal molecules, which would serve as mediators for informational exchange between microorganisms and host’s cells. To check this hypothesis we’ve studied blood of 25 healthy donors and 161 patients with various conditions (peritonitis, endocarditis, infections of urinary tract etc.) using Gas chromatography-Mass spectrometry. In all cases we detected SMOMs-fatty acids (hydroxy-acids, branched, unsaturated and cyclopropanoic acids), aldehydes, alcohol’s and phenyl-carbonic substances, that are never normally synthesized by mammals, but are structural components or metabolites of microorganisms. The quantitative and qualitative characteristics of SMOMs varied significantly in patients from those of healthy people. Substances of low molecular weight—that are the structural components of normal endogenous microflora and dominate in blood of healthy people—have disappeared or were present in very low quantities. Meanwhile concentration of bacterial molecules that are rarely found in healthy persons, has increased by 10–100 times. Other SMOMs, never present in healthy people, were also found. The data obtained stand pro the hypothesis on constant presence of SMOMs in blood of healthy and ill individuals and allow to formulate the Concept on Homeostasis of small molecules originating from microbes; serious break up of this homeostasis (decompensation of SMOM homeostasis) serves as inductor of general inflammatory response, septic shock and multisystem organ failure. Keywords: microbial markers, phenylcarbonic compounds, gas chromatography–mass spectrometry, fatty acids, homeostasis, human blood, non-antibiotics, sepsis.
The Mechanism of Insulin Resistance Caused by HIV Protease Inhibitor Therapy (2000)

Retroviral protease inhibitors used as therapy for HIV-1 infection have been causally associated with serious metabolic side effects, including peripheral lipodystrophy, hyperlipidemia, insulin resistance, and in some cases, overt type 2 diabetes. The etiology of this characteristic clinical syndrome remains unknown. We demonstrate that the HIV protease inhibitor, indinavir, dramatically inhibits insulin-stimulated glucose uptake in 3T3-L1 adipocytes in a dose-dependent manner (63% inhibition observed with 100 micrometer indinavir). Indinavir treatment did not affect early insulin signaling events or the translocation of intracellular Glut1 or Glut4 glucose transporters to the cell surface. To determine whether indinavir may be directly affecting the intrinsic transport activity of glucose transporters, the Glut1 and Glut4 isoforms were heterologously expressed and analyzed in Xenopus laevis oocytes. Indinavir at 100 microm had no effect on Glut1 transport activity in Xenopus oocytes, whereas Glut4 activity was significantly inhibited (45% inhibition). Similar effects on glucose transport were observed for other HIV protease inhibitors. We conclude that HIV protease inhibitors as a class are capable of selectively inhibiting the transport function of Glut4 and that this effect may be responsible for a major iatrogenic complication frequently observed in HIV patients.
Diels−Alder Reaction of 2-Amino-Substituted Furans as a Method for Preparing Substituted Anilines (1997)

5-Amino-2-furancarboxylic acid methyl ester undergoes a facile Diels−Alder cycloaddition with a variety of dienophiles to afford ring-opened cycloadducts that are readily dehydrated using BF3· OEt2 to give polysubstituted anilines. In each case, the cycloaddition proceeds with high regioselectivity, with the electron-withdrawing group being located ortho to the amino group. The most favorable FMO interaction is between the HOMO of the furanamine and the LUMO of the dienophile. The atomic coefficient at the ester carbon of the furan is larger than that at the amino center, and this nicely accommodates the observed regioselectivity. The [4 + 2]-cycloaddition of N-(5-nitrofuranyl)morpholine with methyl vinyl ketone affords a mixture of three phenols. One of the phenols is derived from a Diels−Alder reaction followed by nitro group ejection and subsequent aromatization. The remaining two phenols are the result of cleavage of the initially formed oxabicyclic intermediate with concomitant migration of the nitro group. The mild reaction conditions with which furan-2-carbamic acid tert-butyl ester undergoes Diels−Alder cycloaddition with N-phenylmaleimide allow for the ready isolation of the initial oxybridged cycloadduct.
Catalysis of a protein folding reaction: Thermodynamic and kinetic analysis of subtilisin BPN' interactions with its propeptide fragment (1993)

The in vivo folding of subtilisin is dependent on a 77 amino acid propeptide, which is eventually cleaved from the N-terminus of subtilisin to create the 275 amino acid mature form of the enzyme (Ikemura et al., 1987). We have cloned, expressed, and purified large quantities of the 77 amino acid subtilisin propeptide. This has enabled us to characterize its participation in the subtilisin folding reaction by spectroscopic and microcalorimetric methods. Unfolded subtilisin, when returned to native conditions, is kinetically isolated from its native state. Folding of subtilisin with the native calcium site-A is extremely slow even in the presence of a high concentration of isolated propeptide. The folding of a calcium-free mutant subtilisin, however, is readily catalyzed by the isolated propeptide. The propeptide-subtilisin folding reaction can be described as the following equilibrium: P(u) + S(u)<==>P-S<==>Pf-Sf<==>P(u) + Sf, where S(u) and P(u) are subtilisin and propeptide, respectively, which are largely unstructured at the start of the reaction; P-S is a collision complex of unfolded subtilisin and propeptide; Pf-Sf is the complex of folded subtilisin and propeptide; and Sf is folded subtilisin. The rate-limiting step in the folding reaction of calcium-free mutant subtilisin is formation of the initial collision complex, P-S. The rate at which P(u) and S(u) form a productive collision complex is approximately 500 M-1 s-1. The collision complex appears to be an early folding unit which, once formed, results in rapid isomerization to the fully folded complex. The rate constant for isomerization of the collision complex to the folded complex is > or = 0.5 s-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Immune-stimulating effects of lactic acid bacteria in vivo and in vitro (2010)

The health-promoting effects of lactic acid bacteria (LAB) are well recognised, making them a popular functional food ingredient. Commercially available probiotic products are often promoted as capable of improving immune defences also in healthy subjects. However, while strain-specific differences exist in the effects of LAB, conventional yoghurt bacteria have proved beneficial as well. For comparing the immunological effects of conventional and probiotic LAB, young healthy women received either a commercially available probiotic fermented milk product or a conventional yoghurt for four weeks. Both treatments showed comparable effects resulting in a stronger immunological reaction to stimuli (natural cytotoxicity against cancer cells, mitogen-induced T-lymphocyte activation and stimulated cytokine production). To study the mechanisms behind these effects, conventional (Lactobacillus delbrueckii) and probiotic (Lactobacillus rhamnosus GG), LAB were compared in vitro at the cellular level. Interestingly, L. rhamnosus GG was more potent in inducing maturation of dendritic cells (DC) that play a substantial role in directing the immune response to stimuli. In turn, L. delbrueckii provoked a higher secretion of proinflammatory cytokines as well as IL-10. These effects were, however, observed only after direct incubation of DC and LAB, not when both were separated by a layer of enterocyte-like Caco-2 cells. LAB also induced cytokine secretion in peripheral blood mononuclear cells in a similar manner and this effect was reduced in a Caco-2 cell model, suggesting a modulating influence of gut epithelial cells. While both conventional and probiotic strains modulate the immune response, specific properties may offer therapeutic options in the treatment of certain diseases.
Anti-inflammatory Effects of ElectronicSignal Treatment (2008)

Inflammation often plays a key role in the perpetuation of pain. Chronic inflammatory conditions (e.g. osteoarthritis, immune system dysfunction, micro-circulatory disease, painful neuritis, and even heart disease) have increased as baby boomers age. Medicine’s current antiinflammatory choices are NSAIDs and steroids; the value in promoting cure and side effect risks of these medications are unclear and controversial, especially considering individual patient variations. Electricity has continuously been a powerful tool in medicine for thousands of years. All medical professionals are, to some degree, aware of electrotherapy; those who directly use electricity for treatment know of its anti-inflammatory effects. Electronic signal treatment (EST), as an extension of presently available technology, may reasonably have even more anti-inflammatory effects. EST is a digitally produced alternating current sinusoidal electronic signal with associated harmonics to produce theoretically reasonable and/or scientifically documented physiological effects when applied to the human body. These signals are produced by advanced electronics not possible even 10 to 15 years ago. The potential long-lasting anti-inflammatory effects of some electrical currents are based on basic physical and biochemical facts listed in the text below, namely that of stimulating and signaling effective and long-lasting anti-inflammatory effects in nerve and muscle cells. The safety of electrotherapeutic treatments in general and EST in particular has been established through extensive clinical use. The principles of physics have been largely de-emphasized in modern medicine in favor of chemistry. These electrical treatments, a familiar application of physics, thus represent powerful and appropriate elements of physicians’ pain care armamentaria in the clinic and possibly for prescription for use at home to improve overall patient care and maintenance of quality of life via low-risk and potentially curative treatments. Key words: Electroanalgesia, electronic signal treatment (EST), inflammation, anti-inflammatory effects, immune system, neurogenic inflammation, chronic pain, steroids, NSAIDs, oscillo/torsional effect, cAMP, membrane repair and stabilization, pain care/management
Epigenetic Temporal Control of Mouse Hox Genes in Vivo (2009)

During vertebrate development, the temporal control of Hox gene transcriptional activation follows the genomic order of the genes within the Hox clusters. Although it is recognized that this "Hox clock" serves to coordinate body patterning, the underlying mechanism remains elusive. We have shown that successive Hox gene activation in the mouse embryo is closely associated with a directional transition in chromatin status, as judged by the dynamic progression of transcription-competent modifications: Increases in activation marks correspond to decreases in repressive marks. Furthermore, using a mouse in which a Hox cluster was split into two pieces, we document the necessity to maintain a clustered organization to properly implement this process. These results suggest that chromatin modifications are important parameters in the temporal regulation of this gene family.
Prolyl hydroxylase, protein disulfide isomerase, and other structurally related proteins (1998)

4-Hydroxylase: An Overview, Norberto A. Guzman Prolyl 4-Hydroxylase Inhibitors, Volkmar Gunzler and Klaus Weidmann Occurrence of Dihydroxyproline in Proteins and Peptides, Steven W. Taylor and J. Herbert Waite Distribution and Expression of Prolyl 4-Hydroxylase-Beta Subunit/Protein Disulfide Isomerase in Vertebrate Cells, William V. Everson and Winston W. Y. Kao Prolyl 4-Hydroxylase and Protein Disulfide Isomerase in Plants, Richard A. Dixon and Basil S. Shorrosh Protein Disulfide Isomerase from Soybean: Isolation, Structure, and Function in Protein Folding, Yukio Kawamura, Tetsuya Ookura, and Ken Kainuma Physiological Roles of the Thiol: Protein Disulfide Oxidoreductases, Jordan L. Holtzman HIP-70/GRP58/ERp61/PLC-Alpha/CPT: A Single Gene Product and Member of the Protein Disulfide Isomerase Gene Family with Thiol Oxidoreductase Activity Subject Neuroendocrine Regulation, Charles V. Mobbs, Michael Kaplitt, and Donald Pfaff Estrogen-Responsive Domain of Protein Disulfide Isomerase, Lois T. Hunt, John C. M. Tsibris, and William N. Spellacy Protein Disulfide Isomerase as a Novel Target for ATP, Eric Quemeneur The Thioredoxin System and Thioredoxin Domains of Protein Disulfide Isomerase from the Endoplasmic Reticulum, Johanna Lundstrom-Ljung and Arne Holmgren Chaperone Activity of Protein Disulfide Isomerase, Chih-chen Wang Protein Disulfide Isomerase and the Complications of Protein Folding, Hiram F. Gilbert The Peptide Binding Site of Protein Disulfide Isomerase, Robert Noiva, Sawako Onodera, Melissa D. Schwaller, and William A. Irwin Protein Disulfide Isomerase as a Component of Muscle Sarcoplasmic Reticulum, Shairaz Baksh, Marek Michalak, and Larry Fliegel Microsomal Triglyceride Transfer Protein: A Heterodimer Consisting of Protein Disulfide Isomerase and a Unique Large Subunit, John R. Wetterau Reductive Function of PDI at the Surface of Mammalian Cells: Its Role in Diphtheria Toxin Translocation and HIV Entry into Human Cells, Hugues J.-P. Ryser, Richard Mandel, Angelo Gallina, and Alicia Rivera Structural Analysis of the Beta Subunit of Prolyl 4-Hydroxylase, James A. Bassuk Retina Cognin: A Tissue-Specific PDI-Related Protein Involved in Cell Signaling, Robert E. Hausman, Johanna L. Phillips, Harold Pariser, Vered Holdengreber, and Yehuda Ben-Shaul Protein Disulfide Isomerase: A Putative Calcium Storage Protein in the Endoplasmic Reticulum, Benjamin Kaminer, Djamel Lebeche, and Hector A. Lucero Protein Disulfide Isomerase: Cellular Enzymology of the CXXC Motif, Peter T. Chivers, Martha C. A. Laboissiere, and Ronald T. Raines Protein Disulfide Isomerase: Use in the Production of Recombinant Pharmaceutical Proteins, Janet L. Wolfe
Endothelin and angiotensin II stimulation of Na+-H+ exchange is impaired in cardiac hypertrophy. (1997)

We compared the effects of endothelin-1 (ET-1) on intracellular pH, intracellular [Ca2+]i, and cell contraction in hypertrophied adult ventricular myocytes from ascending aortic banded rats and age-matched controls. Intracellular pH (pH(i)) was measured in individual myocytes with SNARF-1, and [Ca2+]i was measured with indo-1, simultaneous with cell motion. Experiments were performed at 36 degrees C in myocytes paced at 0.5 Hz in Hepes-buffered solution (pH(o) 7.40) containing 1.2 mM CaCl2. At baseline, calibrated pH(i), diastolic and systolic [Ca2+]i values, and the amplitude of cell contraction were similar in hypertrophied and control myocytes. Exposure of the control myocytes to 10 nM ET-1 caused an increase in the amplitude of cell contraction to 163+/-22% of baseline (P < 0.05), associated with intracellular alkalinization (pH(i) + 0.08+/-0.02 U, P < 0.05) and a slight increase in peak systolic [Ca2+]i (104+/-11% of baseline, P < 0.05). In contrast, in the hypertrophied myocytes, exposure to ET-1 did not increase the amplitude of cell contraction or cause intracellular alkalinization (-0.01+/-0.02 U, NS). Similar effects were observed in the hypertrophied and control myocytes in response to exposure to 10 nM angiotensin II. ET-1 also increased the rate of recovery from intracellular acidosis induced by the washout of NH4Cl in the control cells, but did not do so in the hypertrophied cells. In the presence of 10 microM 5-(N-ethyl-N-isopropyl)-amiloride, which inhibits Na+-H+ exchange, ET-1 did not cause a positive inotropic effect or intracellular alkalinization in control cells. The activation of protein kinase C by exposure to phorbol ester caused intracellular alkalinization and it increased the rate of recovery from intracellular acidification induced by an NH4Cl pulse in control cells but not in hypertrophied cells. ET-1, as well as angiotensin II, and phorbol ester, fail to stimulate forward Na+-H+ exchange in adult hypertrophied myocytes. These data suggest a defect in the coupling of protein kinase C signaling with Na+-H+ exchange in adult hypertrophied myocytes.
On the Interpretation of the Hazard Ratio and Communication of Survival Benefit (2017)

This brief communication will clarify the difference between a relative hazard and a relative risk. We highlight the importance of this difference, and demonstrate in practical terms that 1 minus the hazard ratio should not be interpreted as a risk reduction in the commonly understood sense of the term. This article aims to provide a better understanding of the type of risk reduction that a hazard ratio implies, thereby clarifying the intent in the communication among practitioners and researchers and establishing an accurate and realistic foundation for communicating with patients. <b><i>The Oncologist</i></b> 2017;22:484-486.
Measuring Similarity for Security Vulnerabilities (2010)

As the number of software vulnerabilities increases year by year, software vulnerability becomes a focusing point in information security. This paper proposes a vulnerability similarity measurement to compare different vulnerabilities according to a set of criteria. Our approach is based on the structural hierarchy of vulnerabilities, and the similarity is defined using established mathematical models. The National Vulnerability Database and the Ontology of Vulnerability Management provide the information necessary for the similarity calculation. The similarity measurement can be used in many areas of vulnerability management, such as vulnerability classification, mitigation, and patching.
Penciclovir: a review of its spectrum of activity, selectivity, and cross-resistance pattern (1993)

The antiherpesvirus agent penciclovir has been evaluated extensively in cell culture. The spectrum of activity of penciclovir against human herpesviruses is similar to that of acyclovir, both compounds having good activity against herpes simplex viruses types 1 and 2 (HSV-1, HSV-2), varicella-zoster virus (VZV), and Epstein-Barr virus (EBV). Like acyclovir, penciclovir has slight activity against cytomegalovirus (CMV). The susceptibility of recent clinical isolates was not influenced by geographical origin. The activity of penciclovir was examined in several antiviral assays (plaque reduction, virus antigen, virus yield, and viral DNA inhibition) and in many different host cells (fibroblast, epithelial-like, keratinocyte). The comparative activity of penciclovir and acyclovir depended on both the host cell and the assay and, while in certain circumstances penciclovir was more active than acyclovir, overall the activities of the two compounds were considered comparable. Both compounds were highly selective antiviral agents with minimal effects on a wide range of representative, proliferating human cells. The inhibition of a variety of acyclovir-resistant strains has been examined and, as expected, thymidine kinase-negative strains were resistant to both penciclovir and acyclovir. The majority of acyclovir-resistant HSV and VZV clinical strains were cross-resistant to penciclovir. However, certain acyclovir-resistant strains, some of which were of clinical origin and all of which expressed altered thymidine kinase or DNA polymerase, were susceptible to penciclovir. In addition, a series of foscarnet-resistant HSV isolates appeared to be susceptible to both penciclovir and acyclovir. These results led to the evaluation of penciclovir in further cell culture studies, and also in animal models. Furthermore, the mechanism of action of penciclovir has also been investigated. Since the oral absorption of penciclovir in animals was poor, an oral form, famciclovir, was selected which gave improved oral bioavailability of penciclovir.
Architecture of a Database System (2007)

Database Management Systems (DBMSs) are a ubiquitous and critical component of modern computing, and the result of decades of research and development in both academia and industry. Historically, DBMSs were among the earliest multi-user server systems to be developed, and thus pioneered many systems design techniques for scalability and reliability now in use in many other contexts. While many of the algorithms and abstractions used by a DBMS are textbook material, there has been relatively sparse coverage in the literature of the systems design issues that make a DBMS work. This paper presents an architectural discussion of DBMS design principles, including process models, parallel architecture, storage system design, transaction system implementation, query processor and optimizer architectures, and typical shared components and utilities. Successful commercial and open-source systems are used as points of reference, particularly when multiple alternative designs have been adopted by different groups.