gebhart/patrepeval huggingface dataset:
Binding Properties of Neuroligin 1 and Neurexin 1β Reveal Function as Heterophilic Cell Adhesion Molecules (1997)

beta-Neurexins and neuroligins are plasma membrane proteins that are displayed on the neuronal cell surface. We have now investigated the interaction of neurexin 1beta with neuroligin 1 to evaluate their potential to function as heterophilic cell adhesion molecules. Using detergent-solubilized neuroligins and secreted neurexin 1beta-IgG fusion protein, we observed binding of these proteins to each other only in the presence of Ca2+ and in no other divalent cation tested. Only neurexin 1beta lacking an insert in splice site 4 bound neuroligins, whereas neurexin 1beta containing an insert was inactive. Half-maximal binding required 1-3 microM free Ca2+, which probably acts by binding to neuroligin 1 but not to neurexin 1beta. To determine if neurexin 1beta and neuroligin 1 can also interact with each other when present in a native membrane environment on the cell surface, we generated transfected cell lines expressing neuroligin 1 and neurexin 1beta. Upon mixing different cell populations, we found that cells aggregate only if cells expressing neurexin 1beta are mixed with cells expressing neuroligin 1. Aggregation was dependent on Ca2+ and was inhibited by the addition of soluble neurexin 1beta lacking an insert in splice site 4 but not by the addition of neurexin 1beta containing an insert in splice site 4. We conclude that neurexin 1beta and neuroligin 1 (and, by extension, other beta-neurexins and neuroligins) function as heterophilic cell adhesion molecules in a Ca2+-dependent reaction that is regulated by alternative splicing of beta-neurexins.
Immunosuppressive agents in transplantation: Mechanisms of action and current anti-rejection strategies (2000)

Over the past century, the concept of interfering with the immune response at various sites by blocking the formation, stimulation, proliferation, and differentiation of lymphocytes has led to relentless development of new immunosuppressive drugs. These agents are associated with reduced risk of short- and long-term toxicity and have dramatically improved allograft and patient survival, especially in recipients of solid organ transplants. Current protocols in such patients are nearly all calcineurin-inhibitor based, using cyclosporine or tacrolimus, as part of dual, triple, or sequential therapy. This review focuses on agents currently in clinical use at transplant centers in United States. The drugs are described in terms of their basic mechanisms of action, therapeutic uses, clinical studies, and adverse effects. In addition, the efficacy and toxicity of a few promising new therapeutic approaches are examined. Finally, important challenges regarding pharmacological immunosuppression as it relates to solid organ and composite tissue allotransplantation are discussed.
Cardiopulmonary Resuscitation with Interposed Abdominal Compression in Dogs (1982)

This study was conducted to evaluate the hemodynamic effectiveness of a new modification of cardiopulmonary resuscitation (CPR), termed interposed abdominal compression-CPR (IAC-CPR). IAC-CPR utilizes all the steps of standard CPR with the addition of abdominal compressions interposed during the release phase of chest compression. Ventricular fibrillation was induced electrically in 10 anesthetized dogs, and either IAC-CPR or standard CPR was initiated while arterial and venous blood pressures and cardiac output were monitored. The two CPR methods were alternated every 3 minutes over a period of 30 minutes. The addition of interposed abdominal compressions to standard CPR improved arterial pressures and perfusion in 10 of 10 dogs. Brachial arterial blood pressure averaged 87/32 mm Hg during IAC-CPR vs 58/16 mm Hg during standard CPR. Cardiac output (±SE) averaged 24.2 ± 5.7 ml/min/kg during IAC-CPR vs 13.8 ± 2.6 ml/min/kg during standard CPR. IAC-CPR requires no extra mechanical equipment, and, if proven effective in human trials, may improve resuscitation success in the field and in the hospital.
Instant Messaging: Effects of Relevance and Timing (2000)

Instant messaging (IM) has grown rapidly to involve millions of users spanning a variety of platforms. This paper outlines two preliminary studies that examined the effects of IM notifications on ongoing desktop computer productivity tasks. Results from the studies show that the disruptiveness of IM to productivity tasks is reduced if the incoming message is highly relevant to the current task, or if messages are queued until certain key computing operations have been completed. User interface design principles for the control of messaging are proposed based on the results.
A Surface-Exposed Region of a Novel Outer Membrane Protein (P66) of<i>Borrelia</i>spp. Is Variable in Size and Sequence (1998)

A model of the 66-kDa outer membrane protein (P66) of Lyme disease Borrelia spp. predicts a surface-exposed loop near the C terminus. This region contains an antigen commonly recognized by sera from Lyme disease patients. In the present study, this region of P66 and homologous proteins of other Borrelia spp. were further investigated by using monoclonal antibodies, epitope mapping of P66 of Borrelia burgdorferi, and DNA sequencing. A monoclonal antibody specific for B. burgdorferi bound to the portion of P66 that was accessible to proteolysis in situ. The linear epitope for the antibody was mapped within a variable segment of the surface-exposed region. To further study this protein, the complete gene of Borrelia hermsii for a protein homologous to P66 was cloned. The deduced protein was 589 amino acids in length and 58% identical to P66 of B. burgdorferi. The B. hermsii P66 protein was predicted to have a surface-exposed region in the same location as that of B. burgdorferi's P66 protein. With primers designed on the basis of conserved sequences and PCR, we identified and cloned the same regions of P66 proteins of Borrelia turicatae, Borrelia parkeri, Borrelia coriaceae, and Borrelia anserina. The deduced protein sequences from all species demonstrated two conserved hydrophobic regions flanking a surface-exposed loop. The loop sequences were highly variable between different Borrelia spp. in both sequence and size, varying between 35 and 45 amino acids. Although the actual function of P66 of Borrelia spp. is unknown, the results suggest that its surface-exposed region is subject to selective pressure.
Immunization with Hepatitis C Virus-Like Particles Induces Humoral and Cellular Immune Responses in Nonhuman Primates (2004)

We have previously reported the production of hepatitis C virus-like particles (HCV-LP) using a recombinant baculovirus containing the cDNA of the HCV structural proteins (core, E1, and E2). These particles resemble the putative HCV virions and are capable of inducing strong and broad humoral and cellular immune responses in mice. Here we present evidence on the immunogenicity of HCV-LP and the effects of novel adjuvant systems in a nonhuman primate model, the baboon. Three groups of four baboons were immunized with HCV-LP, HCV-LP and adjuvant AS01B (monophosphoryl lipid A and QS21), or HCV-LP and the combination of AS01B and CpG oligodeoxynucleotides 10105. After four immunizations over an 8-month period, all animals developed HCV-specific humoral and cellular immune responses including antibodies to HCV structural proteins and gamma interferon(+) (IFN-gamma(+))CD4(+) and IFN-gamma(+)CD8(+) T-cell responses. The immunogenicity of HCV-LP was only marginally enhanced by the use of adjuvants. The overall HCV-specific immune responses were broad and long lasting. Our results suggest that HCV-LP is a potent immunogen to induce HCV-specific humoral and cellular immune responses in primates and may be a promising approach to develop novel preventive and therapeutic modalities.
Inflammatory Bowel Disease—From Bench to Bedside. (1995)

Inflammatory Bowel Disease—From Bench to Bedside is an important addition to the burgeoning literature on inflammatory bowel disease. Sixtynine authors have contributed to a 773 page volume on the subject. The general theme of the book is increased understanding of the clinical nature of IBD and its management as the result of recent basic research developments. The book is divided into four sections. Section 1 (Introduction) begins with a brief commentary on such important IBD issues as the relationship or independence of Crohn's colitis and ulcerative colitis, the possible role of infectious agents, and the direction of current basic research on IBD. Section 1 concludes with a comprehensive review of the epidemiology of IBD. Section 2 (The Laboratory Bench) includes excellent chapters on the genetics of inflammatory bowel disease, mucosal immune regulation, mechanisms of tissue injury. B-cell dependent mechanisms, cytokines, eicosanoids, role of reactive metabolites of oxygen and...
Ex vivo gene therapy for HIV-1 treatment (2011)

Until recently, progress in ex vivo gene therapy (GT) for human immunodeficiency virus-1 (HIV-1) treatment has been incremental. Long-term HIV-1 remission in a patient who received a heterologous stem cell transplant for acquired immunodeficiency syndrome-related lymphoma from a CCR5(-/-) donor, even after discontinuation of conventional therapy, has energized the field. We review the status of current approaches as well as future directions in the areas of therapeutic targets, combinatorial strategies, vector design, introduction of therapeutics into stem cells and enrichment/expansion of gene-modified cells. Finally, we discuss recent advances towards clinical application of HIV-1 GT.
Human Telomerase Reverse Transcriptase (hTERT) Is a Novel Target of the Wnt/β-Catenin Pathway in Human Cancer (2012)

Telomerase activation plays a critical role in human carcinogenesis through the maintenance of telomeres, but the activation mechanism during carcinogenesis remains unclear. The human telomerase reverse transcriptase (hTERT) promoter has been shown to promote hTERT gene expression selectively in tumor cells but not in normal cells. Deregulation of the Wnt/β-catenin signaling pathway is reported to be associated with human carcinogenesis. However, little is known about whether the Wnt/β-catenin pathway is involved in activating hTERT transcription and inducing telomerase activity (TA). In this study, we report that hTERT is a novel target of the Wnt/β-catenin pathway. Transient activation of the Wnt/β-catenin pathway either by transfection of a constitutively active form of β-catenin or by LiCl or Wnt-3a conditioned medium treatment induced hTERT mRNA expression and elevated TA in different cell lines. Furthermore, we found that silencing endogenous β-catenin expression by β-catenin gene-specific shRNA effectively decreased hTERT expression, suppressed TA, and accelerated telomere shortening. Of the four members of the lymphoid-enhancing factor (LEF)/T-cell factor (TCF) family, only TCF4 showed more effective stimulation on the hTERT promoter. Ectopic expression of a dominant negative form of TCF4 inhibited hTERT expression in cancer cells. Through promoter mapping, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay, we found that hTERT is a direct target of β-catenin·TCF4-mediated transcription and that the TCF4 binding site at the hTERT promoter is critical for β-catenin·TCF4-dependent expression regulation. Given the pivotal role of telomerase in carcinogenesis, these results may offer insight into the regulation of telomerase in human cancer.
Enabling PVM to build parallel multidomain virtual machines (2006)

In this paper, we present a PVM extension which through a middleware solution based on the H2O distributed meta-computing framework, permits us to build a parallel virtual machine composed of hosts located across multidomain clusters. In the H2O framework, we have developed specialized proxy pluglets used to route PVM messages among computational resources placed in different network domains that firewalls can shield should the need arise. The simulation tests that we have performed showed a smaller time overhead in communications across the proxies. However, this is acceptable if we consider the benefits gained in utilizing resources that we can now exploit owing to the fact that they are often located on non-routable private networks. PVM applications can be ported into this system without modifications.
Adenylylcyclase Increases Responsiveness to Catecholamine Stimulation in Transgenic Mice (1999)

The amount of AC sets a limit on cardiac beta-adrenergic signaling in vivo, and increased AC, independent of betaAR number and G-protein content, provides a means to regulate cardiac responsiveness to betaAR stimulation. Overexpressing an effector (AC) does not alter transmembrane signaling except when receptors are activated, in contrast to receptor/G-protein overexpression, which yields continuous activation and has detrimental consequences. Our findings establish the importance of AC content in modulating beta-adrenergic signaling in the heart, suggesting a new target for safely increasing cardiac responsiveness to betaAR stimulation.
Gene Vaccines (2003)

Gene vaccines are a new approach to immunization and immunotherapy in which, rather than a live or inactivated organism (or a subunit thereof), one or more genes that encode proteins of the pathogen are delivered. The goal of this approach is to generate immunity against diseases for which traditional vaccines and treatments have not worked, to improve vaccines, and to treat chronic diseases. Gene vaccines make use of advances in immunology and molecular biology to more specifically tailor immune responses (cellular or humoral, or both) against selected antigens. They are still under development in research and clinical trials. The mechanisms for inducing cellular (as opposed to humoral) responses against a particular antigen have been elucidated. Gene vaccines provide a means to generate specific cellular responses while still generating antibodies, if desired. In addition, by delivering only the genes that encode the particular proteins against which a protective or therapeutic immune response is desired, the potential limitations and risks of certain other approaches can be avoided. This article describes the rationale for, immunologic mechanisms involved in, and design of gene vaccines under development. Preclinical and clinical studies of these vaccines are discussed for various clinical applications, focusing on infectious diseases.
Pharmacology, Toxicology, and Adverse Effects of Synthetic Cannabinoid Drugs. (2014)

Synthetic cannabinoid drugs have become an established part of the recreational drug landscape in the United States and internationally. These drugs are manufactured in clandestine laboratories internationally and distributed in the United States in smoking mixtures, use of which produces effects very similar to use of marijuana. The adverse-effect profile of the drugs has not been studied in humans and infrequently in animal models, so much of the information about their toxicity comes from emergency department and treatment reports and forensic case studies. This review considers the discovery and characterization of the endocannabinoid system, approaches to receptor-binding studies of various synthetic cannabinoids from the first wave of naphthoylindoles (e.g., JWH-018) to the emerging adamantoylindole drugs (e.g., AKB-48), and their analogs, to evaluate the potential activity of drugs in this class. Currently employed approaches to assessing functional activity of the drugs using in vitro and in vivo models is also described, and comparisons made to the effects of THC. The physiological effects of activation of the endocannabinoid system in humans are reviewed, and the physiological effects of cannabinoid use are described. Case reports of adverse events including emergency department admissions, mental health admissions, and clinical and forensic case reports are presented in detail and discussed to summarize the current state of knowledge of adverse effects, both clinical and forensic in humans, including effects on driving ability, and tissue injury and death. The greatest weight is accorded to those reports that include toxicological confirmation of use. Finally, we discuss the current status of attempts to schedule and control the distribution of synthetic cannabinoids and the relevance of receptor binding and functional activity in this context. There is growing toxicological and pharmacological evidence of impairment, psychosis, tissue injury, and isolated deaths attributable to this emerging class of drugs.
Ribozyme, antisense RNA, and antisense DNA inhibition of U7 small nuclear ribonucleoprotein-mediated histone pre-mRNA processing in vitro. (1989)

A comparative analysis of ribozyme, antisense RNA, and antisense DNA inhibitors of the in vitro small nuclear ribonucleoprotein U7-dependent histone pre-mRNA processing reaction was performed. RNA molecules complementary to the U7 sequence inhibited in vitro processing of histone pre-mRNA at a sixfold excess over U7. Single-stranded DNA complementary to the entire U7 sequence inhibited the reaction at a 60-fold excess over U7, while a short, 18-nucleotide DNA molecule complementary to the 5' end of U7 inhibited the processing reaction at a 600-fold excess. A targeted ribozyme was capable of specifically cleaving the U7 small nuclear ribonucleoprotein in a nuclear extract and inhibited the U7-dependent processing reaction, but in our in vitro system it required a 1,000-fold excess over U7 for complete inhibition of processing.
<i>CKS1At</i> overexpression in <i>Arabidopsis thaliana</i> inhibits growth by reducing meristem size and inhibiting cell‐cycle progression (2001)

The SUC1/CKS1 proteins associate with cyclin-dependent kinases (CDKs) and play an essential role in the regulation of the cell cycle. Recently, an Arabidopsis thaliana SUC1/CKS1 homologous gene, designated CKS1At, has been cloned. Here, overexpression of CKS1At in Arabidopsis is shown to reduce leaf size and root growth rates. Reduced root growth resulted primarily from an increase of the cell-cycle duration and a shortening of the meristem. Endoreduplication was unaffected. The increased cell-cycle duration was associated with an equal extension of both the G1 and G2 phases. This inhibition was due to the binding of CDK subunits with CDKs. The reduced growth rates in response to altered cell-cycle gene expression demonstrates a direct dependence of plant growth rates on cell-cycle regulation.
Using OpenMP: Portable Shared Memory Parallel Programming (Scientific and Engineering Computation) (2007)

I hope that readers will learn to use the full expressibility and power of OpenMP. This book should provide an excellent introduction to beginners, and the performance section should help those with some experience who want to push OpenMP to its limits. --from the foreword by David J. Kuck, Intel Fellow, Software and Solutions Group, and Director, Parallel and Distributed Solutions, Intel Corporation OpenMP, a portable programming interface for shared memory parallel computers, was adopted as an informal standard in 1997 by computer scientists who wanted a unified model on which to base programs for shared memory systems. OpenMP is now used by many software developers; it offers significant advantages over both hand-threading and MPI. Using OpenMP offers a comprehensive introduction to parallel programming concepts and a detailed overview of OpenMP. Using OpenMP discusses hardware developments, describes where OpenMP is applicable, and compares OpenMP to other programming interfaces for shared and distributed memory parallel architectures. It introduces the individual features of OpenMP, provides many source code examples that demonstrate the use and functionality of the language constructs, and offers tips on writing an efficient OpenMP program. It describes how to use OpenMP in full-scale applications to achieve high performance on large-scale architectures, discussing several case studies in detail, and offers in-depth troubleshooting advice. It explains how OpenMP is translated into explicitly multithreaded code, providing a valuable behind-the-scenes account of OpenMP program performance. Finally, Using OpenMP considers trends likely to influence OpenMP development, offering a glimpse of the possibilities of a future OpenMP 3.0 from the vantage point of the current OpenMP 2.5. With multicore computer use increasing, the need for a comprehensive introduction and overview of the standard interface is clear. Using OpenMP provides an essential reference not only for students at both undergraduate and graduate levels but also for professionals who intend to parallelize existing codes or develop new parallel programs for shared memory computer architectures.
Big Data for Dummies (2013)

Find the right big data solution for your business or organization Big data management is one of the major challenges facing business, industry, and not-for-profit organizations. Data sets such as customer transactions for a mega-retailer, weather patterns monitored by meteorologists, or social network activity can quickly outpace the capacity of traditional data management tools. If you need to develop or manage big data solutions, you'll appreciate how these four experts define, explain, and guide you through this new and often confusing concept. You'll learn what it is, why it m
Antimicrobial Susceptibility Testing: General Principles and Contemporary Practices (1998)

One of the most important tasks in the clinical microbiology laboratory is the performance of antimicrobial susceptibility tests on significant bacterial isolates. The goal of susceptibility testing is to predict the likely outcome of treating a patient's infection with a particular antimicrobial agent. Empirical therapy continues to be effective for some bacterial pathogens because resistance mechanisms have not yet been acquired or are still rare; examples include penicillin therapy for group A streptococcal infections, erythromycin for legionellosis, and penicillin for N. meningitidis infections in the United States. Susceptibility testing is useful and important for the common bacterial species that are not predictably susceptible to drugs of choice because of acquired resistance mechanisms (e.g., members of the Enterobacteriaceae, Pseudomonas species, Staphylococcus species, Enterococcus species, Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae). The two important and related functions of susceptibility testing are the detection of frank resistance and the quantitative measurement of susceptibility to antimicrobial agents with some species that may have direct therapeutic relevance, e.g., the magnitude of the penicillin and cephalosporin MICs for Streptococcus pneumoniae [1-3].