gebhart/patrepeval huggingface dataset:
Exercise training confers anticipatory protection from sudden death during acute myocardial ischemia. (1994)

Seven conscious dogs documented to be at high risk by the occurrence of ventricular fibrillation (VF) during acute myocardial ischemia were randomly assigned to 6 weeks of either daily exercise training or cage rest followed by exercise training. After 6 weeks of daily treadmill training, heart rate variability, a marker of vagal tone, increased by 74% (P < .001); baroreflex sensitivity, a marker of the capability to reflexly augment vagal activity, increased by 69% (P < .01); the repetitive extrasystole threshold, a marker of ventricular electrical stability, increased by 44% (P < .05). After exercise training, the incidence of ventricular fibrillation during acute myocardial ischemia decreased by 100%, as all animals survived. Neither passage of time nor heart rate level during ischemia contributed to the outcome. The most likely mechanism to explain the striking change in risk status is the shift in autonomic balance characterized by increased cardiac vagal activity, which was previously shown to have an antifibrillatory effect. These results suggest that exercise training in healthy individuals may decrease their likelihood of developing lethal arrhythmias during acute myocardial ischemia.
Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD) (2013)

There is no evidence of effect of SSRIs in children and emerging evidence of harm. There is limited evidence of the effectiveness of SSRIs in adults from small studies in which risk of bias is unclear.
New Mass-Spectrometry-Compatible Degradable Surfactant for Tissue Proteomics (2015)

Tissue proteomics is increasingly recognized for its role in biomarker discovery and disease mechanism investigation. However, protein solubility remains a significant challenge in mass spectrometry (MS)-based tissue proteomics. Conventional surfactants such as sodium dodecyl sulfate (SDS), the preferred surfactant for protein solubilization, are not compatible with MS. Herein, we have screened a library of surfactant-like compounds and discovered an MS-compatible degradable surfactant (MaSDeS) for tissue proteomics that solubilizes all categories of proteins with performance comparable to SDS. The use of MaSDeS in the tissue extraction significantly improves the total number of protein identifications from commonly used tissues, including tissue from the heart, liver, and lung. Notably, MaSDeS significantly enriches membrane proteins, which are often under-represented in proteomics studies. The acid degradable nature of MaSDeS makes it amenable for high-throughput MS-based proteomics. In addition, the thermostability of MaSDeS allows for its use in experiments requiring high temperature to facilitate protein extraction and solubilization. Furthermore, we have shown that MaSDeS outperforms the other MS-compatible surfactants in terms of overall protein solubility and the total number of identified proteins in tissue proteomics. Thus, the use of MaSDeS will greatly advance tissue proteomics and realize its potential in basic biomedical and clinical research. MaSDeS could be utilized in a variety of proteomics studies as well as general biochemical and biological experiments that employ surfactants for protein solubilization.
The IgG Fc Contains Distinct Fc Receptor (FcR) Binding Sites: The Leukocyte Receptors FcγRI and FcγRIIa Bind to a Region in the Fc Distinct from That Recognized by Neonatal FcR and Protein A (2000)

The CH2-CH3 interface of the IgG Fc domain contains the binding sites for a number of Fc receptors including Staphylococcal protein A and the neonatal Fc receptor (FcRn). It has recently been proposed that the CH2-CH3 interface also contains the principal binding site for an isoform of the low affinity IgG Fc receptor II (Fc gamma RIIb). The Fc gamma RI and Fc gamma RII binding sites have previously been mapped to the lower hinge and the adjacent surface of the CH2 domain although contributions of the CH2-CH3 interface to binding have been suggested. This study addresses the question whether the CH2-CH3 interface plays a role in the interaction of IgG with Fc gamma RI and Fc gamma RIIa. We demonstrate that recombinant soluble murine Fc gamma RI and human Fc gamma RIIa did not compete with protein A and FcRn for binding to IgG, and that the CH2-CH3 interface therefore appears not to be involved in Fc gamma RI and Fc gamma RIIa binding. The importance of the lower hinge was confirmed by introducing mutations in the proposed binding site (LL234,235AA) which abrogated binding of recombinant soluble Fc gamma RIIa to human IgG1. We conclude that the lower hinge and the adjacent region of the CH2 domain of IgG Fc is critical for the interaction between Fc gamma RIIa and human IgG, whereas contributions of the CH2-CH3 interface appear to be insignificant.
Gene Therapy for the COL7A1 Gene (2013)

course of disease and therapy vary significantly depending on the present EB subform Blister formation can be restricted to the soles of the feet or occur generalized. Severe systemic complications and extracutaneous manifestations including blistering and erosions of the cornea and mucosal tissues, stenoses or strictures of respiratory, gastrointestinal and urogenital tracts, pylorus atresia, muscular dystrophy and skin cancer are certain complications associated with different EB subtypes So far over 30 distinctive subtypes have been described and classified in a system, which was recently revised See Table A: Classification scheme for the major EB subtypes Major EB type Major EB subtypes Affected proteins EB simplex (EBS) Suprabasal EBS plakophilin-1, desmoplakin; others? Basal EBS keratins 5 & 14; plectin, 64 integrin, BPAG1 Junctional EB (JEB) JEB, Herlitz (JEB-H) laminin-332, (laminin-5) JEB, other laminin-332, type XVII collagen 64 integrin, 3 integrin Dystrophic EB (DEB) Dominant DEB (DDEB) type VII collagen Recessive DEB (RDEB) type VII collagen Kindler syndrome kindlin-1 B: Classification scheme for all known EB simplex subtypes Major types EBS subtypes Affected proteins EBS suprabasal lethal acantholytic EB desmoplakin plakophilin deficiency plakophilin-1 EBS superficialis ? EBS basal EBS, localized (EBS-loc) a K5, K14 EBS, Dowling Meara (EBS-DM) K5, K14 EBS, other generalized (EBS,gen-nonDM) b K5, K14, BPAG1 EBS with mottled pigmentation(EBS-MP) K5 EBS with muscular dystrophy (EBS-MD) plectin EBS with pylorus atresia (EBS-PA) plectin, 64 integrin EBS, autosomal recessive (EBS-AR) K14 EBS, ogna (EBS-Og) plectin EBS, migratory circinate (EBS-migr) K5 (rare variants in italics) a Previously called EBS, Weber-Cockayne b Includes patients previously classified as EBS-Koebner C: Classification scheme for all known junctional subtypes
High level cell‐free expression and specific labeling of integral membrane proteins (2004)

We demonstrate the high level expression of integral membrane proteins (IMPs) in a cell-free coupled transcription/translation system using a modified Escherichia coli S30 extract preparation and an optimized protocol. The expression of the E. coli small multidrug transporters EmrE and SugE containing four transmembrane segments (TMS), the multidrug transporter TehA with 10 putative TMS, and the cysteine transporter YfiK with six putative TMS, were analysed. All IMPs were produced at high levels yielding up to 2.7 mg of protein per mL of reaction volume. Whilst the vast majority of the synthesized IMPs were precipitated in the reaction mixture, the expression of a fluorescent EmrE-sgGFP fusion construct showed evidence that a small part of the synthesized protein 'remained soluble and this amount could be significantly increased by the addition of E. coli lipids into the cell-free reaction. Alternatively, the majority of the precipitated IMPs could be solubilized in detergent micelles, and modifications to the solubilization procedures yielded proteins that were almost pure. The folding induced by formation of the proposed alpha-helical secondary structures of the IMPs after solubilization in various micelles was monitored by CD spectroscopy. Furthermore, the reconstitution of EmrE, SugE and TehA into proteoliposomes was demonstrated by freeze-fracture electron microscopy, and the function of EmrE was additionally analysed by the specific transport of ethidium. The cell-free expression technique allowed efficient amino acid specific labeling of the IMPs with 15N isotopes, and the recording of solution NMR spectra of the solubilized EmrE, SugE and YfiK proteins further indicated a correctly folded conformation of the proteins.
Berry anthocyanins as novel antioxidants in human health and disease prevention (2007)

Edible berries, a potential source of natural anthocyanin antioxidants, have demonstrated a broad spectrum of biomedical functions. These include cardiovascular disorders, advancing age-induced oxidative stress, inflammatory responses, and diverse degenerative diseases. Berry anthocyanins also improve neuronal and cognitive brain functions, ocular health as well as protect genomic DNA integrity. This chapter demonstrates the beneficial effects of wild blueberry, bilberry, cranberry, elderberry, raspberry seeds, and strawberry in human health and disease prevention. Furthermore, this chapter will discuss the pharmacological benefits of a novel combination of selected berry extracts known as OptiBerry, a combination of wild blueberry, wild bilberry, cranberry, elderberry, raspberry seeds, and strawberry, and its potential benefit over individual berries. Recent studies in our laboratories have demonstrated that OptiBerry exhibits high antioxidant efficacy as shown by its high oxygen radical absorbance capacity (ORAC) values, novel antiangiogenic and antiatherosclerotic activities, and potential cytotoxicity towards Helicobacter pylori, a noxious pathogen responsible for various gastrointestinal disorders including duodenal ulcer and gastric cancer, as compared to individual berry extracts. OptiBerry also significantly inhibited basal MCP-1 and inducible NF-kappabeta transcriptions as well as the inflammatory biomarker IL-8, and significantly reduced the ability to form hemangioma and markedly decreased EOMA cell-induced tumor growth in an in vivo model. Overall, berry anthocyanins trigger genetic signaling in promoting human health and disease prevention.
Exploration of antigenic variation in gp120 from clades A through F of human immunodeficiency virus type 1 by using monoclonal antibodies (1994)

The reactivities of a panel of 14 monoclonal antibodies (MAbs) with monomeric gp120 derived from 67 isolates of human immunodeficiency virus type 1 of clades A through F were assessed by using an antigen-capture enzyme-linked immunosorbent assay. The MAbs used were all raised against gp120 or gp120 peptides from clade B viruses and were directed at a range of epitopes relevant to human immunodeficiency virus type 1 neutralization: the V2 and V3 loops, discontinuous epitopes overlapping the CD4-binding site, and two other discontinuous epitopes. Four of the five V3 MAbs showed modest cross-reactivity within clade B but very limited reactivity with gp120s from other clades. These reactivity patterns are consistent with the known primary sequence requirements for the binding of these MAbs. One V3 human MAb (19b), however, was much more broadly reactive than the others, binding to 19 of 29 clade B and 10 of 12 clade E gp120s. The 19b epitope is confined to the flanks of the V3 loop, and these sequences are relatively conserved in clade B and E viruses. In contrast to the limited reactivity of V3 MAbs, CD4-binding site MAbs were much more broadly reactive across clades, two of these MAbs (205-46-9 and 21h) being virtually pan-reactive across clades A through F. Another human MAb (A-32) to a discontinuous epitope was also pan-reactive. The CD4-binding site is strongly conserved between clades; but when considering the epitopes near the CD4-binding site, clade D gp120 appears to be the most closely related to clade B and clade E appears to be the least related. A tentative rank order for these epitopes is B/D-A/C-E/F. V2 MAbs reacted sporadically within and between clades, and no clear pattern was observable. While results from binding assays do not predict neutralization serotypes, they suggest that there may be antigenic subtypes related, but not identical, to the genetic subtypes.
Efficient VHDL models for various PLD architectures (1995)

VHDL is a flexible language for programming PLDs (Programmable Logic Devices) but the way it is synthesized for different architectures varies. Since there are several types of PLDs and several synthesis tools, it is very important for the designer to know which VHDL model to use for a particular architecture in order to achieve maximum efficiency. The term efficiency refers to a good use of resources that result to a denser fit of the logic design into the PLD with a minimum implementation delay. The choice of the VHDL model also depends on the application and the expectations of the designer. Based on the information from several PLD architectures, this thesis points out the maximum efficiency models for each architecture in different aspects of VHDL programming and sequential logic applications. The architectures that the study is focused on, are the Altera MAX family and the Cypress MAX, Flash and CY7C33x families.
Hepatic complications of total parenteral nutrition (1988)

Elevations in serum hepatic enzyme levels and alterations in hepatic morphology have been noted in patients on total parenteral nutrition, in some cases progressing to fatal hepatic failure. Various factors such as toxins, inappropriate substrates, overfeeding, deficiency states, and gut hormone alterations have been implicated. It would appear that the tailoring of nutritional support to meet patient needs and the maintenance of normal gut integrity will be of increasing importance in reducing the incidence of this potentially fatal complication.
Quantitative Analysis and Characterization of Biofunctionalized Fluorescent Silica Particles (2006)

A strategy for the production and subsequent characterization of biofunctionalized silica particles is presented. The particles were engineered to produce a bifunctional material capable of both (a) the attachment of fluorescent dyes for particle encoding and (b) the sequential modification of the surface of the particles to couple oligonucleotide probes. A combination of microscopic and analytical methods is implemented to demonstrate that modification of the particles with 3-aminopropyl trimethoxysilane results in an even distribution of amine groups across the particle surface. Evidence is provided to indicate that there are negligible interactions between the bound fluorescent dyes and the attached biomolecules. A unique approach was adopted to provide direct quantification of the oligonucleotide probe loading on the particle surface through X-ray photoelectron spectroscopy, a technique which may have a major impact for current researchers and users of bead-based technologies. A simple hybridization assay showing high sequence specificity is included to demonstrate the applicability of these particles to DNA screening.
Helicobacter pylori as a Vaccine Delivery System (2007)

For more than 10 years a vaccine against Helicobacter pylori has been the elusive goal of many investigators. The need for a vaccine was highlighted when eradication attempts in developing countries were foiled by reinfection rates of 15-30% per annum. In addition, physicians in developed countries were concerned that attempts at total eradication of H. pylori would result in widespread macrolide resistance in both H. pylori and other important pathogens. Although attempts to produce vaccines against H. pylori have failed in their ultimate goal, considerable knowledge has been developed on the pathogenesis and immunology of Helicobacter infections. In this article we describe an alternative use for this new knowledge, i.e. a plan to use live Helicobacter species to deliver vaccines against other organisms. Because of its intimate attachment to the gastric mucosa and long-term residence there, H. pylori might succeed as an antigen delivery system, a goal which has eluded most other strategies of nonparenteral vaccination.
Antibody remodeling: a general solution to the design of a metal-coordination site in an antibody binding pocket. (1990)

To develop a general approach to designing cofactor-binding sites for catalytic antibodies, we characterized structural patterns in the binding sites of antibodies and zinc enzymes. Superposition of eight sets of antibody light- and heavy-chain variable domains identified structurally conserved sites within the sequence-variable complementarity determining regions. The pattern for catalytic zinc sites included two ligands close in sequence, a sequence-distant ligand, and a main-chain hydrogen bond joining two ligands. In both the light- and heavy-chain variable domains, the stereochemistry of five structurally conserved sites general to all known antibody structures matched that of the zinc ligands of carbonic anhydrase: three residues on two hydrogen-bonded antiparallel beta-strands. For one such general site, an antibody model replacing residue 34 on the first complementarity determining region of the light chain (L1) and residues 89 and 91 on the third complementarity determining region of the light chain (L3) with histidine ligands formed a zinc-binding site with an open coordination position at the bottom of the antibody binding pocket. For the anti-fluorescein antibody 4-4-20, this L1-L3 site placed the zinc ion about 4 A from the bound fluorescein, an indicator for metal binding. This predicted zinc-binding mutant was created in the single-chain variable domain construct, expressed, and found by fluorescence quenching to bind metal ion with an affinity constant of 10(6) M-1. Thus, our template-based multisite design proved successful for remodeling an antibody to contain a cofactor-binding site, without requiring further mutagenesis and screening. Combination of a specific light or heavy chain containing a catalytic metal site with a library of complementary chains raised to potential substrates or transition state analogs should greatly improve the production of catalytic antibodies with desired activities and specificities.
Crizanlizumab for the Prevention of Pain Crises in Sickle Cell Disease (2016)

In patients with sickle cell disease, crizanlizumab therapy resulted in a significantly lower rate of sickle cell-related pain crises than placebo and was associated with a low incidence of adverse events. (Funded by Selexys Pharmaceuticals and others; SUSTAIN ClinicalTrials.gov number, NCT01895361 .).
Integration of pharmaceutical discovery and development : case histories (1998)

Introduction R. Hirschmann. Renin Inhibitors S.H. Rosenberg, H.D. Kleinert. The Discovery and Development of Angiotensin II Antagonists D.J. Carini, et al. Development of an Orally Active Tripeptide Arginal Thrombin Inhibitor R.T. Shuman, P.D. Gesellchen. Discovery and Development of an Endothelin-A Receptor Selective Antagonist PD 156707 A.M. Doherty, A.C.G. Uprichard. Endothelin Receptor Antagonists J.D. Elliott, et al. LHRH Antagonists F. Haviv, et al. LHRH Agonists K.W. Funk, et al. Discovery and Development of Somatostatin Agonists P. Marbach, et al. Factors Impacting the Delivery of Therapeutic Levels of Pyrone-Based HIV Protease Inhibitors G.E. Padbury, et al. The Integration of Medicinal Chemistry, Drug Metabolism, and Pharmaceutical Research and Development in Drug Discovery and Development: The Story of Crixivan(R), an HIV Protease Inhibitor J.H. Lin, et al. De Novo Design and Discovery of Cyclic HIV Protease Inhibitors Capable of Displacing the Active-Site Structural Water Molecule G.V. De Lucca, et al. Discovery and Development of the BHAP Nonnucleoside Reverse Transcriptase Inhibitor Delaviridine Mesylate W.J. Adams, et al. 12 Additional Chapters. Index.
Shape‐ and Nitric Oxide Flux‐Dependent Bactericidal Activity of Nitric Oxide‐Releasing Silica Nanorods (2013)

Silica nanorods (SNRs) are synthesized and then functionalized with aminoalkoxysilanes to prepare a new class of nitric oxide (NO)-releasing materials. The aspect ratio and size of the SNRs are tuned by varying the temperature, pH, and silane concentration used during the surfactant-templated synthesis. N-Diazeniumdiolate nitric oxide (NO) donors are formed on the secondary amine-functionalized SNRs by reaction with NO gas under basic conditions. Particle surface modifications are employed to manipulate the NO release kinetics. The diverse morphology (i.e., aspect ratio ∼1-8), NO-release kinetics (2000-14,000 ppb NO/mg particle) and similar sizes (i.e., particle volume ∼0.02 μm³) of the resulting NO-releasing SNRs facilitates further studies of how particle shape and NO flux impacts bactericidal activity against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Pseudomonas aeruginosa (P. aeruginosa) bacteria. The bactericidal efficacies of these materials improves with increasing particle aspect ratio and initial NO flux. Both chemical (i.e., NO-release kinetics) and physical (i.e., morphology) properties greatly influenced the bactericidal activity of these materials.
Abstract 18549: Effects of AMR101, a Pure Eicosapentaenoic Omega-3 Fatty Acid, on the Fatty Acid Profile in Plasma and Red Blood Cells in Statin-Treated Patients With Persistent High Triglycerides (Results from the ANCHOR Study) (2012)

AMR101 is an omega-3 fatty acid (FA) investigational new drug containing ≥96% pure icosapent ethyl, the ethyl ester of eicosapentaenoic acid (EPA). This subanalysis of the ANCHOR study evaluated the effects of AMR101 on the FA profiles and relationships between AMR101 and triglyceride (TG) lowering in plasma and RBCs. ANCHOR was a phase 3, double-blind, 12-week clinical study in high-risk statin-treated patients with residually high TG levels (≥200 and &lt;500 mg/dL) despite LDL cholesterol control (≥40 and &lt;100 mg/dL). Patients (N=702) on stable diet were randomized to AMR101 4 g/d, 2 g/d, or placebo. Twenty eight FAs were measured in plasma and RBCs for 153 patients using a gas chromatography/flame ionization detection method. Mean baseline plasma EPA levels were 20, 27, and 24 μg/g for AMR101 4 g/d, 2 g/d, and placebo, respectively; Mean placebo-adjusted EPA levels increased by 650% (P&lt;0.0001) and 268% (P&lt;0.0001) with AMR101 4 g/d and 2 g/d by week 12. Mean baseline plasma EPA expressed as percentage of total FAs (mol%) was 0.4, 0.5, and 0.5% for AMR101 4 g/d, 2 g/d, and placebo, respectively. Mean plasma EPA (mol%) at Week 12 was 3.6, 1.9, and 0.5% for AMR101 4 g/d, 2 g/d, and placebo, respectively. Levels of the EPA metabolite omega-3 docosapentaenoic acid also increased with both doses of AMR101 (P&lt;0.0001). The arachidonic acid (AA)/EPA plasma ratio has been suggested to be useful as a biomarker for arteriosclerotic disease. Mean placebo-adjusted AA/EPA plasma ratio decreased from baseline by 90% (P&lt;0.0001) and 75% (P&lt;0.0001) with AMR101 4 g/d and 2 g/d. Total omega-3 FAs increased and total omega-6 FAs decreased with both doses of AMR101 (P&lt;0.0001). Similar results were observed in RBCs. Increased doses of AMR101 resulted in increased EPA levels and corresponded with reductions in TG. The TG-lowering effect of AMR101 was due to the increase in EPA, as there were no statistically significant changes in plasma docosahexaenoic acid concentrations. Overall, AMR101 significantly increased EPA in plasma and RBCs in a linear, dose-dependent fashion consistent with its TG-lowering effect and caused other shifts in FA concentration and RBC membrane content that may have clinical benefit.