gebhart/patrepeval huggingface dataset:
Caspase-cleaved HPK1 induces CD95L-independent activation-induced cell death in T and B lymphocytes (2007)

Life and death of peripheral lymphocytes is strictly controlled to maintain physiologic levels of T and B cells. Activation-induced cell death (AICD) is one mechanism to delete superfluous lymphocytes by restimulation of their immunoreceptors and it depends partially on the CD95/CD95L system. Recently, we have shown that hematopoietic progenitor kinase 1 (HPK1) determines T-cell fate. While full-length HPK1 is essential for NF-kappaB activation in T cells, the C-terminal fragment of HPK1, HPK1-C, suppresses NF-kappaB and sensitizes toward AICD by a yet undefined cell death pathway. Here we show that upon IL-2-driven expansion of primary T cells, HPK1 is converted to HPK1-C by a caspase-3 activity below the threshold of apoptosis induction. HPK1-C selectively blocks induction of NF-kappaB-dependent antiapoptotic Bcl-2 family members but not of the proapoptotic Bcl-2 family member Bim. Interestingly, T and B lymphocytes from HPK1-C transgenic mice undergo AICD independently of the CD95/CD95L system but involving caspase-9. Knock down of HPK1/HPK1-C or Bim by small interfering RNA shows that CD95L-dependent and HPK1/HPK1-C-dependent cell death pathways complement each other in AICD of primary T cells. Our results define HPK1-C as a suppressor of antiapoptotic Bcl-2 proteins and provide a molecular basis for our understanding of CD95L-independent AICD of lymphocytes.
Alignment blur in coherently averaged images (1996)

Blurring of coherently averaged images due to imperfect alignment is studied, and two restoration methods are proposed and evaluated. It is shown that iterative realignment is more powerful than post-filtering in reducing blur. The value of averaging and restoration is illustrated on human subjects in noisy video sequences.
Novel large signal mathematical model of MM-wave gtinn device (2005)

The nonlinear characteristic of Gunn device is analyzed on the basis of device physics. A novel mathematical representation of the large signal dynamic characteristic of the Gunn device is presented.
High-frequency irreversible electroporation for cardiac ablation using an asymmetrical waveform (2019)

We therefore conclude that the use of the aHF enhances the feasibility of the HF-IRE method.
High-Relaxivity Magnetic Resonance Imaging Contrast Agents Part 2 (2010)

Water/proton exchange dynamics in the inner- and second-coordination sphere can be predictably tuned by choice of donor atoms and second-sphere substituents, resulting in high-relaxivity agents.
Autoreactive T cell responses show proinflammatory polarization in diabetes but a regulatory phenotype in health (2004)

According to the quality of response they mediate, autoreactive T cells recognizing islet beta cell peptides could represent both disease effectors in the development of type 1 diabetes (T1DM) and directors of tolerance in nondiabetic individuals or those undergoing preventative immunotherapy. A combination of the rarity of these cells, inadequate technology, and poorly defined epitopes, however, has hampered examination of this paradigm. We have identified a panel of naturally processed islet epitopes by direct elution from APCs bearing HLA-DR4. Employing these epitopes in a sensitive, novel cytokine enzyme-linked immunosorbent spot assay, we show that the quality of autoreactive T cells in patients with T1DM exhibits extreme polarization toward a proinflammatory Th1 phenotype. Furthermore, we demonstrate that rather than being unresponsive, the majority of nondiabetic, HLA-matched control subjects also manifest a response against islet peptides, but one that shows extreme T regulatory cell (Treg, IL-10-secreting) bias. We conclude that development of T1DM depends on the balance of autoreactive Th1 and Treg cells, which may be open to favorable manipulation by immune intervention.
Inhibition of Aminopeptidase and Acetylcholinesterase by Puromycin and Puromycin Analogs (1981)

Puromycin analogs in which the o-methyl-L-tyrosine moiety was substituted by a number of amino acids were examined as inhibitors of the puromycin-sensitive rat brain aminopeptidase and bovine erythrocyte acetylcholinesterase. In the case of the aminopeptidase, the structure and stereochemistry of the amino acid substituent were important factors in determining inhibitor effectiveness. In the case of the acetylcholinesterase reaction, the aminonucleoside of puromycin was nearly as effective an inhibitor as puromycin itself, with little effect dependent of the nature or stereochemistry of the amino acid.
Constructing Bayesian-network models of software testing and maintenance uncertainties (1997)

The lifetime of many software systems is surprisingly long, often far exceeding initial plans and expectations. During software evolution and maintenance, developers and managers frequently gain or lose confidence in software artifacts, especially when existing uncertainties are relieved or new ones are encountered. Fluctuations in developers' confidences may in turn affect process actions or decisions, e.g. in determining the impact of change, whether regression testing is needed or when to stop testing. We present an approach that allows developers' confidences or “beliefs” regarding software components to be modeled and updated directly. This approach is part of an overall strategy that calls for explicit modeling of software uncertainties using the technique called Bayesian belief networks. Initially, we present several kinds of software uncertainty and how they may be modeled. This is followed by introducing Bayesian belief networks and how they may be used to either confirm, evaluate or predict software uncertainties. We discuss our experiences in constructing Bayesian-network models for an existing software system under development at Beckman Instruments. Once constructed, these models may be used by developers and managers in future software understanding, evolution and maintenance activities. We also list several factors that may affect confidence as identified in conjunction with the Beckman study. Finally, we describe the design and implementation of a Java program that allows software systems and associated beliefs to be modeled explicitly
Immunoglobulin‐bearing B cells reconstitute and maintain the murine Ly‐1 B cell lineage (1986)

Previous reconstitution studies in irradiated mice distinguished Ly-1 B from other B cells. The predominant B cell populations in spleen and lymph node are readily reconstituted from progenitors present in adult bone marrow. Ly-1 B cells, in contrast, are reconstituted from cells in peritoneum rather than bone marrow. Further studies, presented here, demonstrate that Ly-1 B populations are reconstituted from peritoneal cells that already express both surface immunoglobulin (IgM) and Ly-1, that is, Ly-1 B. Such cells reconstitute and maintain the Ly-1 B population in irradiated recipients for at least 6 months.
Breast tumor PDXs are genetically plastic and correspond to a subset of aggressive cancers prone to relapse (2013)

Patient derived xenografts (PDXs) are increasingly appreciated models in cancer research, particularly for preclinical testing, as they reflect the patient's tumor biology more accurately than cancer cell lines. We have established a collection of 20 breast PDXs and characterized their biological and clinical features, as well as their genetic stability. While most PDXs originated from triple negative breast cancers (70%), our collection comprised five ER + cases (25%). Remarkably, the tumors that produced PDXs derived from a subset of aggressive breast cancers with a high proportion of grade 3 tumors and reduced recurrence-free survival. Consistent with this, we found significant differences between the transcriptomic signatures of tumors that produced a PDX (Take) and those that did not (No Take). The PDXs faithfully recapitulate the histological features of their primary tumors, and retain an excellent conservation of molecular classification assignment and Copy Number Change (CNC). Furthermore, the CNC profiles of different PDXs established from the same tumor overlap significantly. However, a small fraction of CNCs in the primary tumor that correspond to oligoclonal events were gradually lost during sequential passaging, suggesting that the PDXs' genetic structure eventually stabilizes around a dominant clone present in the tumor of origin. Finally, de novo occurring genetic events covering up to 9% of the genome were found in only a minority of the PDXs, showing that PDXs have limited genetic instability. These data show that breast cancer PDXs represent a subset of aggressive tumors prone to relapse, and that despite of an excellent conservation of original features, they remain genetically dynamic elements.
Thermodynamic criteria for high hit rate antisense oligonucleotide design (2003)

Antisense oligonucleotides are used for therapeutic applications and in functional genomic studies. In practice, however, many of the oligonucleotides complementary to an mRNA have little or no antisense activity. Theoretical strategies to improve the 'hit rate' in antisense screens will reduce the cost of discovery and may lead to identification of antisense oligonucleotides with increased potency. Statistical analysis performed on data collected from more than 1000 experiments with phosphorothioate-modified oligonucleotides revealed that the oligo-probes, which form stable duplexes with RNA (DeltaG(o)37 < or = -30 kcal/mol) and have small self-interaction potential, are more frequently efficient than molecules that form less stable oligonucleotide-RNA hybrids or more stable self-structures. To achieve optimal statistical preference, the values for self-interaction should be (DeltaG(o)37) > or = -8 kcal/mol for inter-oligonucleotide pairing and (DeltaG(o)37) > or = -1.1 kcal/mol for intra-molecular pairing. Selection of oligonucleotides with these thermodynamic values in the analyzed experiments would have increased the 'hit rate' by as much as 6-fold.
Characterization of a New Virus-neutralizing Epitope that Denotes a Sequential Determinant on the Rabies Virus Glycoprotein (1989)

Two new monoclonal antibodies (MAbs) derived from mice immunized with the Pitman-Moore (PM) strain of rabies virus were used to identify and characterize two unique antigenic determinants on the rabies virus glycoprotein. One of the determinants, which defined an additional antigenic site on the rabies virus glycoprotein, was delineated as a distinct epitope by the newly generated MAb, 6-15C4, in competitive binding studies and by comparative antigenic analysis of neutralization-resistant variant viruses. Both antigenic determinants were compared with the five previously described antigenic sites which bind virus-neutralizing antibodies on the challenge virus standard (CVS) and Evelyn-Rokitnicki-Abelseth (ERA) strain glycoproteins. The results presented in this communication show that the 6-15C4 epitope is the first epitope described in the rabies virus glycoprotein that does not depend on the native conformation of the glycoprotein for binding virus-neutralizing antibody. These data suggest that it may be possible to generate a synthetic peptide vaccine against rabies.
Use of olanzapine in non-psychotic psychiatric disorders (2001)

The history of antipsychotic medications begins in the 1950s with chlorpromazine, developed originally as an antihistamine but found to be an aid in the reduction of symptoms of delusions and hallucinations. This phenothiazine derivative was followed by numerous others in the same class (e.g., thioridazine) and then by antipsychotics in other classes (e.g., the popular haloperidol of the butyrophenone class). This group of medications is associated with a number of unpleasant side effects and complications. These included extrapyramidal symptoms (EPS), orthostatic hypotension, hyperprolactinemia and last, but certainly not least, tardive dyskinesia (TD). As a consequence, other alternative antipsychotics were developed in which D(2) blockade effect generally associated with EPS and TD was offset by 5-HT(2) antagonism. The first of this class was clozapine; however, it is associated with agranulocytopenia of sudden onset as well as seizure induction. However, olanzapine, a close structural relative, was soon synthesised for treatment of psychosis and particularly schizophrenia (Zyprexatrade mark, Eli Lilly). It was released in the US in November 1996 with FDA approval for that indication. However, antipsychotics have always been used for other psychiatric disorders, aside from schizophrenia. This includes, in particular, mania, where chlorpromazine use predated lithium as an effective treatment. Other uses for antipsychotics have included other mood disorders, dementia, childhood disorders and personality problems. Here, information on the application of olanzapine to non-schizophrenic disorders is reviewed. Despite the fact that the research post-dates FDA approval in 1996, there was already sufficient evidence for olanzapine's effectiveness in acute mania to obtain approval from the US FDA in March 2000. Other research supports its use as adjunctive therapy in depressive disorders. Phase IV studies and case reports have found limited support for olanzapine's use in a variety of other psychiatric disorders, behavioural disorders of dementia (including Alzheimer's disease), pervasive developmental disorder of childhood, obsessive-compulsive disorder and borderline personality disorder. In each of these latter diagnoses, double-blind studies are either underway or are planned to establish efficacy.
Effect of site-directed mutagenic alterations on ADP-ribosyltransferase activity of the A subunit of Escherichia coli heat-labile enterotoxin (1991)

Previous studies of the S1 subunit of pertussis toxin, an NAD(+)-dependent ADP-ribosyltransferase, suggested that a small amino-terminal region of amino acid sequence similarity to the active fragments of both cholera toxin and Escherichia coli heat-labile enterotoxin represents a region containing critical active-site residues that might be involved in the binding of the substrate NAD+. Other studies of two other bacterial toxins possessing ADP-ribosyltransferase activity, diphtheria toxin and Pseudomonas exotoxin A, have revealed the presence of essential glutamic acid residues vicinal to the active site. To help determine the relevance of these observations to activities of the enterotoxins, the A-subunit gene of the E. coli heat-labile enterotoxin was subjected to site-specific mutagenesis in the region encoding the amino-terminal region of similarity to the S1 subunit of pertussis toxin delineated by residues 6 through 17 and at two glutamic acid residues, 110 and 112, that are conserved in the active domains of all of the heat-labile enterotoxin variants and in cholera toxin. Mutant proteins in which arginine 7 was either deleted or replaced with lysine exhibited undetectable levels of ADP-ribosyltransferase activity. However, limited trypsinolysis of the arginine 7 mutants yielded fragmentation kinetics that were different from that yielded by the wild-type recombinant subunit or the authentic A subunit. In contrast, mutant proteins in which glutamic acid residues at either position 110 or 112 were replaced with aspartic acid responded like the wild-type subunit upon limited trypsinolysis, while exhibiting severely depressed, but detectable, ADP-ribosyltransferase activity. The latter results may indicate that either glutamic acid 110 or glutamic acid 112 of the A subunit of heat-labile enterotoxin is analogous to those active-site glutamic acids identified in several other ADP-ribosylating toxins.
Synthesis of Monodisperse Pt Nanocubes and Their Enhanced Catalysis for Oxygen Reduction (2007)

Monodisperse 8 nm Pt nanocubes are synthesized by reducing Pt(acac)2 in the presence of oleic acid, oleylamine, and a trace amount of Fe(CO)5. Self-assembly of these nanocubes results in a (100) textured array. The nanocubes show an enhanced catalysis toward oxygen reduction, and their specific activity is over twice as high as that from the commercial Pt nanoparticles.
Quantification of mutant huntingtin protein in cerebrospinal fluid from Huntington’s disease patients (2015)

CHDI Foundation Inc.; Medical Research Council (MRC) UK; National Institutes for Health Research (NIHR); Rosetrees Trust; Swedish Research Council; and Knut and Alice Wallenberg Foundation.
Aminopyridines for symptomatic treatment in multiple sclerosis (2002)

Based on currently available information, no unbiased statement can be made about the safety or efficacy of aminopyridines for treating MS symptoms. Furthermore, we could not obtain any data on three unpublished RCTs involving more than 300 participants. We conclude that publication bias remains a pervasive problem in this area, and that until the results of these unpublished studies are available to the scientific community, no confident estimate of effectiveness of aminopyridines in the management of MS symptoms is possible.
Cyclic AMP-Dependent Catabolite Repression Is the Dominant Control Mechanism of Metabolic Fluxes under Glucose Limitation in Escherichia coli (2008)

Although a whole arsenal of mechanisms are potentially involved in metabolic regulation, it is largely uncertain when, under which conditions, and to which extent a particular mechanism actually controls network fluxes and thus cellular physiology. Based on (13)C flux analysis of Escherichia coli mutants, we elucidated the relevance of global transcriptional regulation by ArcA, ArcB, Cra, CreB, CreC, Crp, Cya, Fnr, Hns, Mlc, OmpR, and UspA on aerobic glucose catabolism in glucose-limited chemostat cultures at a growth rate of 0.1 h(-1). The by far most relevant control mechanism was cyclic AMP (cAMP)-dependent catabolite repression as the inducer of the phosphoenolpyruvate (PEP)-glyoxylate cycle and thus low tricarboxylic acid cycle fluxes. While all other mutants and the reference E. coli strain exhibited high glyoxylate shunt and PEP carboxykinase fluxes, and thus high PEP-glyoxylate cycle flux, this cycle was essentially abolished in both the Crp and Cya mutants, which lack the cAMP-cAMP receptor protein complex. Most other mutations were phenotypically silent, and only the Cra and Hns mutants exhibited slightly altered flux distributions through PEP carboxykinase and the tricarboxylic acid cycle, respectively. The Cra effect on PEP carboxykinase was probably the consequence of a specific control mechanism, while the Hns effect appears to be unspecific. For central metabolism, the available data thus suggest that a single transcriptional regulation process exerts the dominant control under a given condition and this control is highly specific for a single pathway or cycle within the network.
How and Why Do Plants Inactivate Homologous (Trans)genes? (1995)

Gene silencing in transgenic plants has emerged in the last 5 years as a topic of intense interest for both applied and basic plant scientists. From the applied side, gene silencing has come as an unwelcome surprise. Early reviews of the prospects for plant genetic engineering did not pinpoint this as a potential obstacle. Rather, the anticipated challenge was to identify tissueand stage-specific promoters that could be used to obtain regulated transgene expression. Yet, silencing of transgenes is turning out to be a substantial problem, as described recently in an aptly titled review, Transgene Inactivation: Plants Fight Back! (Finnegan and McElroy, 1994). According to this article, of 30 companies polled, nearly all reported some problems with unwanted silencing of transgenes. While companies are struggling to find ways to avoid silencing, a small cadre of basic scientists has become fascinated by the phenomenon and is analyzing a variety of silencing systems. To this latter group, the phenomenon of silencing represents more than just an unwanted response to foreign genes; rather, it has opened a door that might lead to a deeper understanding of previously unsuspected ways that plants naturally use homologous or complementary nucleic acid sequences to modify gene expression, both in the nucleus at the DNA level and in the nucleus or cytoplasm as a means to control excess production of mRNA or replication of RNA pathogens. Initial studies of transgenic plants concentrated on those showing tissue-specific and/or high levels of expression. Plants that did not exhibit the desired expression characteristics were usually discarded. It was only a matter of time, however, until such plants would begin to be treated as objects of scientific investigation in their own right. In the late 1980s, papers started to appear that were devoted solely to describing cases of silencing that involved transgene/transgene or transgene/endogenous gene interactions. A central feature of all of these studies was that silencing was associated with multiple copies of homologous DNA sequences, which could comprise protein-coding regions, promoters, or both. Although the initial impulse was to lump these first cases together as a single phenomenon, it has since become clear that several different mechanisms are probably involved. These different mechanisms are united, however, in the sense that they all involve variations on nucleic acid interactions: DNA-DNA, RNA-RNA, and DNA-RNA. A general term that encompasses all of these phenomena is homology-dependent gene silencing. Numerous detailed reviews of this topic are available (Jorgensen, 1992; Matzke and Matzke, 1993; Flavell, 1994; Matzke et al., 1994b; Mol et al., 1994).
Reduction of Ribonucleotides (1979)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Insulin increases CSF Aβ42 levels in normal older adults (2003)

These findings are consistent with recent in vitro studies of insulin effects on Abeta and support the notion that insulin may modulate Abeta42 levels acutely in humans.
Dental Pulp Cells for Induced Pluripotent Stem Cell Banking (2010)

Defined sets of transcriptional factors can reprogram human somatic cells to induced pluripotent stem (iPS) cells. However, many types of human cells are not easily accessible to minimally invasive procedures. Here we evaluated dental pulp cells (DPCs) as an optimal source of iPS cells, since they are easily obtained from extracted teeth and can be expanded under simple culture conditions. From all 6 DPC lines tested with the conventional 3 or 4 reprogramming factors, iPS cells were effectively established from 5 DPC lines. Furthermore, determination of the HLA types of 107 DPC lines revealed 2 lines homozygous for all 3 HLA loci and showed that if an iPS bank is established from these initial pools, the bank will cover approximately 20% of the Japanese population with a perfect match. Analysis of these data demonstrates the promising potential of DPC collections as a source of iPS cell banks for use in regenerative medicine.
Epidemiological and Laboratory Studies of Power Frequency Electric and Magnetic Fields (1992)

A LONG history of lore suggests that magnetism and electricity influence human health, generally for the better. For example, more than 200 years ago, Dr Anton Mesmer attracted worldwide attention with his claim to cure a variety of diseases through exposure to magnetism (and thus, "Mesmerism").<sup>1</sup>Reports are now appearing that magnetic fields may be harmful to health. Whether 200 years from now our progeny will look back at this concern as superstition, as we do at Mesmerism, or as the discovery of a new field of health science, is not yet clear. <h3>BACKGROUND</h3> Electric and magnetic fields (EMF) surround all electrical conductors, including power lines, household wiring, and appliances. There are two components to EMF, electrical and magnetic, that under usual circumstances occur together, but the magnitude of each varies independently. Since the magnitude of the electric field component is determined by voltage, the electric fields are generally