gebhart/patrepeval huggingface dataset:
Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B (2015)

Bromodomains are acetyl-lysine specific protein interaction domains that have recently emerged as a new target class for the development of inhibitors that modulate gene transcription. The two closely related bromodomain containing proteins BAZ2A and BAZ2B constitute the central scaffolding protein of the nucleolar remodeling complex (NoRC) that regulates the expression of noncoding RNAs. However, BAZ2 bromodomains have low predicted druggability and so far no selective inhibitors have been published. Here we report the development of GSK2801, a potent, selective and cell active acetyl-lysine competitive inhibitor of BAZ2A and BAZ2B bromodomains as well as the inactive control compound GSK8573. GSK2801 binds to BAZ2 bromodomains with dissociation constants (KD) of 136 and 257 nM for BAZ2B and BAZ2A, respectively. Crystal structures demonstrated a canonical acetyl-lysine competitive binding mode. Cellular activity was demonstrated using fluorescent recovery after photobleaching (FRAP) monitoring displacement of GFP-BAZ2A from acetylated chromatin. A pharmacokinetic study in mice showed that GSK2801 had reasonable in vivo exposure after oral dosing, with modest clearance and reasonable plasma stability. Thus, GSK2801 represents a versatile tool compound for cellular and in vivo studies to understand the role of BAZ2 bromodomains in chromatin biology.
Development of a “reverse capture” autoantibody microarray for studies of antigen‐autoantibody profiling (2006)

Diagnosing cancers based on serum profiling is a particularly attractive concept. However, the technical challenges to analysis of the serum proteome arise from the dynamic range of protein amounts. Cancer sera contain antibodies that react with a unique group of autologous cellular antigens, which affords a dramatic amplification of signal in the form of antibodies relative to the amount of the corresponding antigens. The serum autoantibody repertoire from cancer patients might, therefore, be exploited for antigen-antibody profiling. To date, studies of antigen-antibody reactivity using microarrays have relied on recombinant proteins or synthetic peptides as arrayed features. However, recombinant proteins and/or synthetic peptides may fail to accurately detect autoantibody binding due to the lack of proper PTMs. Here we describe the development and use of a "reverse capture" autoantibody microarray. Our "reverse capture" autoantibody microarray is based on the dual-antibody sandwich immunoassay platform of ELISA, which allows the antigens to be immobilized in their native configuration. As "proof-of-principle", we demonstrate its use for antigen-autoantibody profiling with sera from patients with prostate cancer and benign prostate hyperplasia.
Freeze-Drying/Lyophilization of Pharmaceutical and Biological Products (2016)

Glimpses into the Realm of Freeze-Drying - Fundamental Issues. Structural and Dynamic Properties of Bulk and Confined Water. Mechanisms of Protein Stabilization During Freeze-Drying and Storage: The Relative Importance of Thermodynamic Stabilizationand Glassy State Relaxation Dynamics. Freezing and Annealing Phenomenon in Lyophilization. Freezing- and Drying-Induced Perturbations of Protein Structure andMechanisms of Protein Protection by Stabilizing Additives. Molecular Mobility of Freeze-Dried Formulations as Determined by NMR Relaxation, and its Effect on Storage Stability. Formulation Characterization. Practical Aspects of Freeze-Drying ofPharmaceutical and Biological Products Using Non-Aqueous Co-solvent Systems. Closure and Container Considerations in Lyophilization. Advanced Glass-Ware for Freeze-DryingCritical steps in the Preparation of Elastomeric Closures for BiopharmaceuticalFreeze-Dried Products. Development of a new Concept for Bulk Freeze-Drying: LYOGUARD Freeze Dry Packaging. Regulatory Control of Freeze-Dried Products: Importance and Evaluation of Residual Moisture. Freeze-Drying of Biological Standards. IndustrialFreeze-Drying for Pharmaceutical Applications. Development of Process Data In a Pilot Plant Transferable to Production. Technical Procedures for Operation of Cleaning-in-Place and Sterilization-in-Place Process for Production Freeze-Drying Equipment.Freeze-Drying Cycle Parameters Global Validation by Using Integral HFT Systems. Lyophilizer Qualification: Some Practical Advice. Lyophilization Process Validation. A New Development: Irradiation of Pharmaceutical and Biological Products. Some LeadingEdge Prospects in Freeze-Drying
Atrial septal thickness and area in normal heart specimens and in those with ostium secundum atrial septal defects (1979)

This anatomic study suggests that an understanding of the thickness of the atrial septum should allow better visualization of most portions of the blade-shaped atrial septum during cross-sectional echocardiography, both in normal subjects and in patients with ostium secundum atrial septal defects. The thickness measurements also demonstrate that difficulties in imaging the atrial septum are a function of resolution limits of existing echocardiographic equipment.
Recombinant Galectin-1 and Its Genetic Delivery Suppress Collagen-Induced Arthritis via T Cell Apoptosis (1999)

Galectin-1 (GAL-1), a member of a family of conserved beta-galactoside-binding proteins, has been shown to induce in vitro apoptosis of activated T cells and immature thymocytes. We assessed the therapeutic effects and mechanisms of action of delivery of GAL-1 in a collagen-induced arthritis model. A single injection of syngeneic DBA/1 fibroblasts engineered to secrete GAL-1 at the day of disease onset was able to abrogate clinical and histopathological manifestations of arthritis. This effect was reproduced by daily administration of recombinant GAL-1. GAL-1 treatment resulted in reduction in anticollagen immunoglobulin (Ig)G levels. The cytokine profile in draining lymph node cells and the anticollagen IgG isotypes in mice sera at the end of the treatment clearly showed inhibition of the proinflammatory response and skewing towards a type 2-polarized immune reaction. Lymph node cells from mice engaged in the gene therapy protocol increased their susceptibility to antigen-induced apoptosis. Moreover, GAL-1-expressing fibroblasts and recombinant GAL-1 revealed a specific dose-dependent inhibitory effect in vitro in antigen-dependent interleukin 2 production to an A(q)-restricted, collagen type 2-specific T cell hybridoma clone. Thus, a correlation between the apoptotic properties of GAL-1 in vitro and its immunomodulatory properties in vivo supports its therapeutic potential in the treatment of T helper cell type 1-mediated autoimmune disorders.
Self—Consistent Molecular Orbital Methods. XII. Further Extensions of Gaussian—Type Basis Sets for Use in Molecular Orbital Studies of Organic Molecules (1972)

Two extended basis sets (termed 5–31G and 6–31G) consisting of atomic orbitals expressed as fixed linear combinations of Gaussian functions are presented for the first row atoms carbon to fluorine. These basis functions are similar to the 4–31G set [J. Chem. Phys. 54, 724 (1971)] in that each valence shell is split into inner and outer parts described by three and one Gaussian function, respectively. Inner shells are represented by a single basis function taken as a sum of five (5–31G) or six (6–31G) Gaussians. Studies with a number of polyatomic molecules indicate a substantial lowering of calculated total energies over the 4–31G set. Calculated relative energies and equilibrium geometries do not appear to be altered significantly.
Electroactive polymers and rapid prototyping : symposium held November 26-30, 2001, Boston, Massachusetts, U.S.A (2002)

This book contains the proceedings of two symposia held at the 2001 MRS Fall Meeting in Boston. Electroactive polymers (EAPs) continue to emerge from anonymity to the spotlight of the science and engineering community. The characteristics of inducing large displacements, lightweight, easy processing, low cost and the functionality to emulate biological muscles are making EAPs attractive for consideration in an increasing number of applications. To make these materials actuators-of choice, however, it is necessary to solidify the technical foundations and identify niche applications where their unique capabilities provide the necessary edge. Papers focus on a wide range of these issues, from fundamental materials understanding and characterization, to new material development, to novel device concepts and demonstrations. Papers also outline many different rapid prototyping approaches including fused deposition of ceramics, stereolithography, microstamping, directed assembly, plasma spray, laser particle guidance, MAPLE DW, laser CVD, micropen, inkjet and several novel liquid or droplet microdispensing approaches.
Correction: Coadministration of Lopinavir/Ritonavir and Rifampicin in HIV and Tuberculosis Co-Infected Adults in South Africa (2013)

Background: In HIV-infected patients receiving rifampicin-based treatment for tuberculosis (TB), the dosage of lopinavir/ ritonavir (LPV/r) is adjusted to prevent sub-therapeutic lopinavir concentrations. In this setting, South African clinicians were advised to administer super-boosted LPV/r (400 mg/400 mg) twice daily, instead of standard dosed LPV/r (400 mg/100 mg) twice daily. We sought to determine -in routine practice -the tolerability and HIV treatment outcomes associated with super-boosted LPV/r compared to unadjusted LPV/r in combination with rifampicin-based TB treatment.
Changes in Myocardial Electrical Impedance Induced by Coronary Artery Occlusion in Pigs With and Without Preconditioning (1997)

A rapid impairment of myocardial impedance occurs after 30 minutes of coronary occlusion, and its onset is better defined by shift in phase angle than by rise in tissue resistivity. Phase 1b arrhythmias are associated with marked impedance changes, and both are delayed by preconditioning. Reversion of ST-segment elevation is partially associated with impairment of myocardial impedance, but other factors play a role as well.
Mixed Azide-Terminated Monolayers:  A Platform for Modifying Electrode Surfaces (2006)

We have prepared and characterized mixed self-assembled monolayers (SAM) on gold electrodes from azido alkane thiols and various omega-functionalized alkane thiols. In the presence of copper(I) catalysts, these azide-modified surfaces are shown to react rapidly and quantitatively with terminal acetylenes forming 1,2,3-triazoles, via "click" chemistry. The initial azide substituents can be identified and monitored using both grazing-angle infrared (IR) and X-ray photoelectron spectrosopies. Acetylenes possessing redox-active ferrocene substituents react with the azide-terminated mixed SAMs and electrochemical measurements of the ferrocene-modified SAM electrodes have been used to quantify the redox centers attached to these platforms. Time-resolved electrochemical measurements have enabled us to follow the formation of these ferrocene centers and thus to measure the rate of the surface "click" reaction. Under optimal conditions this well-behaved second-order reaction takes place with a rate constant of 1 x 10(3) M(-)(1) s(-)(1). Typical reaction times of several minutes were realized using micromolar concentrations of acetylene. These techniques have been used to construct well-characterized, covalently modified monolayers that can be employed as functional electrode surfaces.
Proteolytic Processing of the Open Reading Frame 1b-Encoded Part of Arterivirus Replicase Is Mediated by nsp4 Serine Protease and Is Essential for Virus Replication (1999)

The open reading frame (ORF) 1b-encoded part of the equine arteritis virus (EAV) replicase is expressed by ribosomal frameshifting during genome translation, which results in the production of an ORF1ab fusion protein (345 kDa). Four ORF1b-encoded processing products, nsp9 (p80), nsp10 (p50), nsp11 (p26), and nsp12 (p12), have previously been identified in EAV-infected cells (L. C. van Dinten, A. L. M. Wassenaar, A. E. Gorbalenya, W. J. M. Spaan, and E. J. Snijder, J. Virol. 70:6625-6633, 1996). In the present study, the generation of these four nonstructural proteins was shown to be mediated by the nsp4 serine protease, which is the main viral protease (E. J. Snijder, A. L. M. Wassenaar, L. C. van Dinten, W. J. M. Spaan, and A. E. Gorbalenya, J. Biol. Chem. 271:4864-4871, 1996). Mutagenesis of candidate cleavage sites revealed that Glu-2370/Ser, Gln-2837/Ser, and Glu-3056/Gly are the probable nsp9/10, nsp10/11, and nsp11/12 junctions, respectively. Mutations which abolished ORF1b protein processing were introduced into a recently developed infectious cDNA clone (L. C. van Dinten, J. A. den Boon, A. L. M. Wassenaar, W. J. M. Spaan, and E. J. Snijder, Proc. Natl. Acad. Sci. USA 94:991-997, 1997). An analysis of these mutants showed that the selective blockage of ORF1b processing affected different stages of EAV reproduction. In particular, the mutant with the nsp10/11 cleavage site mutation Gln-2837-->Pro displayed an unusual phenotype, since it was still capable of RNA synthesis but was incapable of producing infectious virus.
The exclusive induction of extinction is gated by BDNF (2010)

We have previously reported that the reconsolidation and extinction of hippocampal-dependent contextual fear memory can be initiated by a single context conditioned stimulus (CS) presentation of either short or long duration, and that both processes require protein synthesis in this brain region. Furthermore, reconsolidation depends on Zif268 activity in this region. Here we show that by infusing a recombinant brain-derived neurotrophic factor (rBDNF) directly into the brain of rats, that high levels of mature BDNF in the hippocampus at retrieval constrain the extinction of the fear memory after prolonged memory recall. We also show after a short CS exposure that reconsolidation was impaired using antisense oligonucleotides targeting Zif268, and that, similarly, reductions in conditioned behavior were observed after prolonged CS presentation when extinction is constrained by high levels of BDNF. This is direct evidence that in the mammalian brain extinction proceeds exclusively after prolonged CS exposure. In addition, that BDNF activity in the hippocampus contributes to a molecular switch for the extinction of hippocampal-dependent memory.
gerbil: Genotype resolution and block identification using likelihood (2004)

The abundance of genotype data generated by individual and international efforts carries the promise of revolutionizing disease studies and the association of phenotypes with individual polymorphisms. A key challenge is providing an accurate resolution (phasing) of the genotypes into haplotypes. We present here results on a method for genotype phasing in the presence of recombination. Our analysis is based on a stochastic model for recombination-poor regions ("blocks"), in which haplotypes are generated from a small number of core haplotypes, allowing for mutations, rare recombinations, and errors. We formulate genotype resolution and block partitioning as a maximum-likelihood problem and solve it by an expectation-maximization algorithm. The algorithm was implemented in a software package called GERBIL (genotype resolution and block identification using likelihood), which is efficient and simple to use. We tested GERBIL on four large-scale sets of genotypes. It outperformed two state-of-the-art phasing algorithms. The phase algorithm was slightly more accurate than GERBIL when allowed to run with default parameters, but required two orders of magnitude more time. When using comparable running times, GERBIL was consistently more accurate. For data sets with hundreds of genotypes, the time required by phase becomes prohibitive. We conclude that GERBIL has a clear advantage for studies that include many hundreds of genotypes and, in particular, for large-scale disease studies.
Invited Review: Effects of different activity and inactivity paradigms on myosin heavy chain gene expression in striated muscle (2001)

The goal of this mini-review is to summarize findings concerning the role that different models of muscular activity and inactivity play in altering gene expression of the myosin heavy chain (MHC) family of motor proteins in mammalian cardiac and skeletal muscle. This was done in the context of examining parallel findings concerning the role that thyroid hormone (T(3), 3,5,3'-triiodothyronine) plays in MHC expression. Findings show that both cardiac and skeletal muscles of experimental animals are initially undifferentiated at birth and then undergo a marked level of growth and differentiation in attaining the adult MHC phenotype in a T(3)/activity level-dependent fashion. Cardiac MHC expression in small mammals is highly sensitive to thyroid deficiency, diabetes, energy deprivation, and hypertension; each of these interventions induces upregulation of the beta-MHC isoform, which functions to economize circulatory function in the face of altered energy demand. In skeletal muscle, hyperthyroidism, as well as interventions that unload or reduce the weight-bearing activity of the muscle, causes slow to fast MHC conversions. Fast to slow conversions, however, are seen under hypothyroidism or when the muscles either become chronically overloaded or subjected to intermittent loading as occurs during resistance training and endurance exercise. The regulation of MHC gene expression by T(3) or mechanical stimuli appears to be strongly regulated by transcriptional events, based on recent findings on transgenic models and animals transfected with promoter-reporter constructs. However, the mechanisms by which T(3) and mechanical stimuli exert their control on transcriptional processes appear to be different. Additional findings show that individual skeletal muscle fibers have the genetic machinery to express simultaneously all of the adult MHCs, e.g., slow type I and fast IIa, IIx, and IIb, in unique combinations under certain experimental conditions. This degree of heterogeneity among the individual fibers would ensure a large functional diversity in performing complex movement patterns. Future studies must now focus on 1) the signaling pathways and the underlying mechanisms governing the transcriptional/translational machinery that control this marked degree of plasticity and 2) the morphological organization and functional implications of the muscle fiber's capacity to express such a diversity of motor proteins.
The risk of transmission of human immunodeficiency virus in dental practice. (1992)

After a decade of study of the acquired immunodeficiency syndrome (AIDS) there is evidence to address the concerns of dental staff about possible transmission of human immunodeficiency virus (HIV). This paper reviews that evidence which demonstrates an extremely low risk of transmission of HIV to staff and patients. Only a few isolated cases have implicated transmission during dental practice, however, there are no proven cases where seroconversion has been demonstrated in relation to an exposure during dental treatment.
CD2 Costimulation Reveals Defective Activity by Human CD4+CD25hi Regulatory Cells in Patients with Multiple Sclerosis (2011)

Studying the activity of homogeneous regulatory T cell (Treg) populations will advance our understanding of their mechanisms of action and their role in human disease. Although isolating human Tregs exhibiting low expression of CD127 markedly increases purity, the resulting Treg populations are still heterogeneous. To examine the complexity of the Tregs defined by the CD127 phenotype in comparison with the previously described CD4(+)CD25(hi) subpopulations, we subdivided the CD25(hi) population of memory Tregs into subsets based on expression of CD127 and HLA-DR. These subsets exhibited differences in suppressive capacity, ability to secrete IL-10 and IL-17, Foxp3 gene methylation, cellular senescence, and frequency in neonatal and adult blood. The mature, short telomere, effector CD127(lo)HLA-DR(+) cells most strongly suppressed effector T cells within 48 h, whereas the less mature CD127(lo)HLA-DR(-) cells required 96 h to reach full suppressive capacity. In contrast, whereas the CD127(+)HLA-DR(-) cells also suppressed proliferation of effector cells, they could alternate between suppression or secretion of IL-17 depending upon the stimulation signals. When isolated from patients with multiple sclerosis, both the nonmature and the effector subsets of memory CD127(lo) Tregs exhibited kinetically distinct defects in suppression that were evident with CD2 costimulation. These data demonstrate that natural and not induced Tregs are less suppressive in patients with multiple sclerosis.
Detection of metastatic neuroblastoma in bone marrow: when is routine marrow histology insensitive? (1997)

Except at diagnosis and relapse when gross disease is present, marrow sampling by histology has limited sensitivity. Current practice grossly underestimates the true prevalence of marrow disease.
Structural analysis of the mouse chromosomal gene encoding interleukin 4 which expresses B cell, T cell and mast cell stimulating activities (1987)

Based on homology with the mouse interleukin 4 (IL-4) cDNA that expresses B cell, T cell, and mast cell stimulating activities (Lee, F. et al., (1986) Proc. Natl. Acad. Sci. USA 83, 2061), we have isolated from a Balb/c mouse liver DNA library the mouse chromosomal gene and analyzed its overall structure. The gene occurs as a single copy in the haploid genome and contains four exons and three introns. The exon sequences almost completely match the cloned cDNA sequence. Interestingly, there is a fairly high degree of homology between mouse IL-4 and mouse IL-2 genes extending more than 200 bp upstream of a "TATA" like sequence located 20 bp upstream of the transcription initiation site. These sequences may play an important role in the regulated expression of this gene in concanavalin A or antigen-stimulated T lymphocytes. The supernatant of COS7 cells transfected with plasmid DNA containing the entire gene exhibited both T cell growth factor and mast cell growth factor activities.