gebhart/patrepeval huggingface dataset:
Leflunomide Suppresses TNF-Induced Cellular Responses: Effects on NF-κB, Activator Protein-1, c-Jun N-Terminal Protein Kinase, and Apoptosis (2000)

Leflunomide is a pyrimidine biosynthesis inhibitor that has recently been approved for treatment of rheumatoid arthritis. However, the mechanism of leflunomide's antiarthritis activity and is not fully understood. The critical role that TNF plays in rheumatoid arthritis led us to postulate that leflunomide blocks TNF signaling. Previously, we have demonstrated that leflunomide inhibits TNF-induced NF-kappaB activation by suppressing I-kappaBalpha (inhibitory subunit of NF-kappaB) degradation. We in this study show that leflunomide also blocks NF-kappaB reporter gene expression induced by TNFR1, TNFR-associated factor 2, and NF-kappaB-inducing kinase (NIK), but not that activated by the p65 subunit of NF-kappaB, suggesting that leflunomide acts downstream of NIK. Leflunomide suppressed TNF-induced phosphorylation of I-kappaBalpha, as well as activation of I-kappaBalpha kinase-beta located downstream to NIK. Leflunomide also inhibited TNF-induced activation of AP-1 and the c-Jun N-terminal protein kinase activation. TNF-mediated cytotoxicity and caspase-induced poly(ADP-ribose) polymerase cleavage were also completely abrogated by treatment of Jurkat T cells with leflunomide. Leflunomide suppressed TNF-induced reactive oxygen intermediate generation and lipid peroxidation, which may explain most of its effects on TNF signaling. The suppressive effects of leflunomide on TNF signaling were completely reversible by uridine, indicating a critical role for pyrimidine biosynthesis in TNF-mediated cellular responses. Overall, our results suggest that suppression of TNF signaling is one of the possible mechanisms for inhibitory activity of leflunomide against rheumatoid arthritis.
Aminotransferase Elevations in Healthy Adults Receiving 4 Grams of Acetaminophen Daily (2006)

Initiation of recurrent daily intake of 4 g of acetaminophen in healthy adults is associated with ALT elevations and concomitant treatment with opioids does not seem to increase this effect. History of acetaminophen ingestion should be considered in the differential diagnosis of serum aminotransferase elevations, even in the absence of measurable serum acetaminophen concentrations.
Genes encoding homologues of three consecutive enzymes in the butyrate/butanol-producing pathway of Clostridium acetobutylicum are clustered on the Clostridium difficile chromosome (1994)

Screening of a Clostridium difficileψEMBL3 gene library with antisera raised against C. difficile culture supernatant identified several clones expressing a 31-kDa protein. A 1.8-kb HindIII fragment subcloned from one of the clones was sufficient for expression of the 31-kDa polypeptide. Southern blot analysis showed a region homologous to this fragment to be present in all of 13 different C. difficile strains tested. Sequence analysis of the 1.8-kb fragment revealed three adjacent open reading frames. A database search showed that these three open reading frames appeared to encode homologues of three consecutive enzymes in the butanol/butyrate-producing pathway of Clostridium acetobutylicum (crotonase, β-hydroxybutyryl coenzyme A dehydrogenase and thiolase).
Role of the α2-Integrin in Osteoblast-specific Gene Expression and Activation of the Osf2 Transcription Factor (1998)

Extracellular matrix molecules such as type I collagen are required for the adhesion, migration, proliferation, and differentiation of a number of cell types including osteoblasts. Matrix components often affect cell function by interacting with members of the integrin family of cell surface receptors. Previous work showed that collagen matrix synthesis, induced by addition of ascorbic acid to cells, precedes and is essential for the expression of osteoblast markers and induction of the osteocalcin promoter in murine MC3T3-E1 cells. This later response requires OSE2, the promoter element recognized by Osf2 (also called Cbfa1/AML3/PEBP2alphaA), a recently identified osteoblast-specific transcription factor. Osteoblasts express several integrins including alpha2beta1 which is a major receptor for type I collagen. This paper examines the role of the alpha2-integrin subunit in osteocalcin promoter activation and osteoblast differentiation. Disruption of alpha2-integrin-ECM interactions with a blocking antibody or DGEA peptide containing the cell-binding domain of type I collagen blocked activation of the mouse osteocalcin gene 2 promoter by ascorbic acid as well as induction of endogenous osteocalcin mRNA and mineralization. Furthermore, anti-alpha2-integrin blocking antibody or peptide reduced ascorbic acid-dependent binding of Osf2 to OSE2 without affecting levels of transcription factor mRNA. Time course studies revealed that ascorbic acid-dependent binding of Osf2 to OSE2 preceded increases in osteocalcin and bone sialoprotein expression and this increase in Osf2 binding was not accompanied by comparable changes in levels of transcription factor mRNA or protein. Taken together, these studies demonstrate that an alpha2-integrin-collagen interaction is required for activation of Osf2 and induction of osteoblast-specific gene expression. Furthermore, matrix signals may regulate Osf2 through a post-translational pathway or via an accessory factor.
Fumaric acid esters, their place in the treatment of psoriasis (2004)

Fumaric acid esters (FAE) have evolved as a therapy for psoriasis through an unusual route, beginning with self‐experimentation by the German chemist Schweckendiek whose premise was that psoriasis might be due to an aberration of the citric acid cycle. While this is not the case, our understanding of the active moiety, its mode of action and place in psoriasis therapy are still developing. However, there is cumulating evidence that dimethylfumarate (DMF), the main ingredient of the marketed mixture, is the active compound. Hoefnagelet al. recently reported on the long‐term effects and safety of FAE1 and Mrowietz et al. published a consensus statement regarding the appropriate use of this therapy in psoriasis in 1998.2 An article in this issue of the journal3 is among the first to explore the possibilities of combination therapy, adding FAE to other second line drugs to treat patients with more difficult and severe psoriasis that is unresponsive to conventional modalities.
Rapid clearance of transfused murine red blood cells is associated with recipient cytokine storm and enhanced alloimmunogenicity (2011)

Three separate insults to RBCs (storage, phenylhydrazine, or heat treatment) result in rapid posttransfusion clearance, with a recipient proinflammatory cytokine storm and enhanced alloimmunogenicity. These data are consistent with the hypothesis that rapid clearance of RBCs is causally involved in these outcomes and suggest that human donor RBCs with favorable posttransfusion clearance profiles may be less immunogenic.
Neuroprotective Effect of Bexarotene in the SOD1G93A Mouse Model of Amyotrophic Lateral Sclerosis (2015)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive weakness and muscle atrophy related to the loss of upper and lower motor neurons (MNs) without a curative treatment. There is experimental evidence suggesting that retinoids may be involved in ALS pathogenesis. Bexarotene (Bxt) is a retinoid-X receptor agonist used in the treatment of cutaneous lymphoma with a favorable safety profile whose effects have been recently investigated in other neurodegenerative diseases. In this study, we analyze the potential therapeutic effect of Bxt in the SOD1(G93A) mouse model of ALS. Mice were treated with Bxt or vehicle five times per week from day 60 onward. Survival, weight, and neuromuscular function studies together with histological and biochemical analyses were performed. Bxt significantly delayed motor function deterioration, ameliorated the loss of body weight, and extended mice survival up to 30% of the symptomatic period. Histological analyses of the lumbosacral spinal cord revealed that Bxt markedly delayed the early motor-neuron degeneration occurring at presymptomatic stages in ALS-transgenic mice. Bxt treatment contributed to preserve the MN homeostasis in the SOD1(G93A) mice. Particularly, it reduced the neuronal loss and the chromatolytic response, induced nucleolar hypertrophy, decreased the formation of ubiquitylated inclusions, and modulated the lysosomal response. As an agonist of the retinoic-X receptor (RXR) pathway, Bxt notably increased the nuclear expression of the RXRα throughout transcriptionally active euchromatin domains. Bxt also contributed to protect the MN environment by reducing reactive astrogliosis and preserving perisomatic synapsis. Overall, these neuroprotective effects suggest that treatment with Bxt could be useful in ALS, particularly in those cases related to SOD1 mutations.
High-Throughput Methods for Detection of Genetic Variation (2001)

Understanding human genetic variation is currently believed to reveal the cause of individual susceptibility to disease and the large variation observed in response to treatment. In this review, we will focus on different approaches to identify and visualize genetic alterations. The various approaches for allele discrimination are formally systematically divided into (i) enzymatic approaches, in which the properties of different enzymes to discriminate between nucleotides are used (restriction enzymes type II, Cleavase and Resolvase, DNA polymerase, and ligase); (ii) electrophoretic methods, in which the allele discrimination is based on the difference in mobility in polymeric gels or capillaries (single- and double-stranded conformation assays, heteroduplex analysis, and DNA sequencing); (iii) solid-phase determination of allelic variants, including high-density oligonucleotide arrays for hybridization analysis, minisequencing primer extension analysis, and fiberoptic DNA sensor array; (iv) chromatographic methods such as denaturing high-performance liquid chromatography (DHPLC); (v) other physical methods of discrimination of allelic variants such as mass spectrometry (mass and charge) or fluorescence exchange-based techniques; and (vi) in silico methods such as high-throughput analysis of expressed sequence tag data. The most frequently used techniques and instrumental settings applied in different combinations are described, and other methods that are less broadly used but have interesting potentials are discussed.
Reactions of Horseradish Peroxidase with Azide. Evidence for a Methionine Residue at the Active Site* (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTReactions of Horseradish Peroxidase with Azide. Evidence for a Methionine Residue at the Active Site*Arthur S. Brill and Ira WeinrybCite this: Biochemistry 1967, 6, 11, 3528–3535Publication Date (Print):November 1, 1967Publication History Published online1 May 2002Published inissue 1 November 1967https://pubs.acs.org/doi/10.1021/bi00863a026https://doi.org/10.1021/bi00863a026research-articleACS PublicationsRequest reuse permissionsArticle Views1902Altmetric-Citations37LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Experimental research on inter-vehicle communication using infrared rays (2002)

A prototype inter-vehicle communication system for intelligent transport systems, using infrared rays, has been developed and successfully demonstrated. In this study, our efforts have mainly focused on protocol development. For inter-vehicle communication, a very quick transmission cycle, high adaptability to vehicle formation change and high data reliability are required. In this paper, we have proposed new communication protocol which satisfies these requirements. In the experiment, four test vehicles equipped with the prototype system were run on a test track. Actual communication was carried out with vehicles running in various situations successfully and status maps for adjacent vehicles were obtained from the received data.
Nuclear factor EF-1A binds to the adenovirus E1A core enhancer element and to other transcriptional control regions. (1989)

We have identified a cellular enhancer-binding protein, present in nuclear extracts prepared from human and rodent cells, that binds to the adenovirus E1A enhancer element I sequence. The factor has been termed EF-1A, for enhancer-binding factor to the E1A core motif. EF-1A was found to bind to two adjacent, related sequence motifs in the E1A enhancer region (termed sites A and B). The binding of EF-1A to these adjacent sites, or to synthetic dimerized sites of either motif, was cooperative. The cooperative binding of EF-1A to these sites was not subject to strict spacing constraints. EF-1A also bound to related sequences upstream of the E1A enhancer region and in the polyomavirus and adenovirus E4 enhancer regions. The EF-1A-binding region in the E1A enhancer stimulated expression of a linked gene in human 293 cells when multimerized. Based on the contact sites for EF-1A binding determined by chemical interference assays, this protein appears to be distinct from any previously characterized nuclear binding protein.
Structural model for the reaction mechanism of glutamine synthetase, based on five crystal structures of enzyme-substrate complexes (1994)

Glutamine synthetase brings nitrogen into metabolism by condensing ammonia and glutamate, with the aid of ATP, to yield glutamine, ADP, and inorganic phosphate. Here we present five crystal structures of GS complexed with each of two substrates, Glu and AMPPNP (an ATP analog), with a transition-state analogue, L-methionine-S-sulfoximine, and with each of two products, Gln and ADP. GS of the present study is from Salmonella typhimurium, has Mn2+ bound, and is fully unadenylylated. Protein-metal-substrate interactions and small but significant conformational changes induced by substrate binding are defined by Fourier maps. On the basis of these maps, we propose a tentative structure-based enzymatic mechanism of glutamine synthesis with these steps: (1) ATP binds first at the top of the funnel-shaped active site cavity, adjacent to the n2 Mn2+; Arg 359 moves toward the Glu binding site. (2) Glu binds adjacent to the n1 Mn2+ at the bottom of the active site near a flexible loop (residues 324-328). As proposed earlier by Meister and others, Glu attacks the gamma-phosphorus atom of ATP to produce gamma-glutamyl phosphate and ADP. (3) The presence of ADP (but not ATP) moves Arg 339 toward the Pi site, perhaps stabilizing the gamma-glutamyl phosphate, and moves Asp 50' of the adjacent subunit toward a putative ammonium ion site, enhancing binding of this third substrate. Deprotonation of the ammonium ion, perhaps by Asp 50', permits the resulting active species, ammonia, to attack the gamma-glutamyl phosphate, forming a tetrahedral intermediate.(ABSTRACT TRUNCATED AT 250 WORDS)
Generation and amplification of ultrashort pulses in erbium, neodymium, and thulium fibers. (1996)

The motivation for this work is to develop a compact, high energy, and ultrashort pulses in a rare earth doped fiber-based laser system. A passively mode-locked femtosecond fiber laser based on the nonlinear polarization evolution technique has the stability problem due to thermal and mechanical perturbations. We demonstrate an environmentally stable mode-locked fiber laser by adding a Faraday rotator mirror and wave plates to compensate the linear phase delay and control the polarization state. The basic mode-locking operation of the environmentally stable laser is analyzed by Jones matrix representations. Experimental results show that the environmentally stable mode-locked 1.56 $\mu$m erbium doped silica fiber laser generates a near transform limited pulse of 125 fs with a repetition rate of 44 MHz. The absorption at 1.06 $\mu$m is very weak in thulium doped ZBLAN/fluoride fiber by measuring the absorption spectrum. However, a strong emission at 0.8 $\mu$m is observed by pumping at 1.06 $\mu$m in thulium doped ZBLAN/fluoride fiber. A threshold behavior is observed when plotting the transmission versus the input pump power. This threshold of the input pump power is the characteristic of the avalanche upconversion. Therefore, a five-level model including an excited state absorption and cross-relaxations is proposed and this model can well explain the weak absorption of 1.06 $\mu$m and the strong emission at 0.8 $\mu$m. Experimentally, we demonstrate a thulium doped ZBLAN multimode fiber amplifier with a single pass gain of 31 dB based on the chirped pulse amplification technique. The output pulse energy is greater than 14 $\mu$J before the damage occurs in the fiber. We also demonstrate a high conversion efficiency of 26% upconversion mode-locked laser in a thulium doped ZBLAN multimode fiber and the output pulse width is 380 ps at a repetition rate of 80 MHz.
Boundary Layer and Pressure Measurements on a Cylinder with Unsteady Circulation Control (1993)

Unsteady boundary-layer and surface pressure measurements were made on a circular cylinder with timevarying blowing applied from a narrow spanwise slot. The effects of mean blowing level, blowing frequency, and boundary-layer trip location were examined at a Reynolds number of 2.2 X 105 based on cylinder diameter. Timeresolved pressures were recorded using pressure sensors located on the Coanda surface and around the circumference of the cylinder. Flush-mounted hot film probes were positioned both upstream and downstream of the slot to provide a qualitative measurement of the boundary-layer characteristics. The results have shown that the shear stress just downstream of the slot was always in-phase with the plenum pressure. However, increasing reduced frequency generally resulted in increasingly larger phase lags between the application of blowing and the development of the flow over the remainder of the Coanda surface. For both steady and unsteady blowing, the jet entrained the outer flow at the slot and remained attached to the Coanda surface, provided a fully attached laminar or turbulent boundary layer was obtained just prior to reaching the slot.
Surface Proteins and Exotoxins Are Required for the Pathogenesis ofStaphylococcus aureusPneumonia (2006)

A model of Staphylococcus aureus-induced pneumonia in adult, immunocompetent C57BL/6J mice is described. This model closely mimics the clinical and pathological features of pneumonia in human patients. Using this system, we defined a role for S. aureus strain Newman surface proteins and secreted exotoxins in pneumonia-related mortality.
Detuned loading effect and high-speed modulation of fiber grating semiconductor lasers (1998)

We have studied both theoretically and experimentally the detuned-loading effect of a fiber grating semiconductor laser. This effect is observed experimentally with a fiber grating semiconductor laser constructed with a single-angled facet diode and a conically lensed grating. Operation of such a laser is demonstrated at 2.5 Gb/s and good eye diagrams are obtained.
Nutrition and chemosensory perception in the elderly (1993)

The elderly person's perception of foods and food flavor is affected by age-associated changes in the chemical senses (taste, smell, and trigeminal sensation). Both classic and modern psychophysical techniques have been applied to achieve some understanding of these changes. Taste threshold sensitivity declines with age; however, the magnitude of the decline and the degree to which taste qualities are differentially affected remains to be understood. Suprathreshold taste intensity perception is affected by age, but there is a differential effect of taste quality. Experiments with blended foods have indicated that both olfactory and taste deficits contribute to older people's difficulty with food identification. Experiments assessing threshold sensitivity, suprathreshold intensity, and suprathreshold identification have all demonstrated significant impairment in olfaction in old age. In fact, these effects are far greater than in the taste system. Patients with Alzheimer's disease show even greater olfactory deficits than normal elderly and the effect is related to the degree of dementia. We have ruled out nasal disease in these patients as the primary causes of olfactory insensitivity, because significant impairment remains when the influence of nasal airflow and nasal cytology has been removed statistically. Both normal elderly and patients with Alzheimer's disease show impairment in odor memory. Sensitivity to, familiarity with, and identifiability of the odors all play a role in odor memory performance. Flavor preference also changes over the lifespan. Older subjects, for instance, rate high concentration of sugar and salt as pleasanter than young subjects do. Multiple influences contribute to this phenomenon. Elderly persons and those of lower nutritional status have shown preferences for higher concentrations of casein hydrolysate than young persons and those of higher nutritional status, suggesting that dietary preference can be related to chemosensory cues. There are significant age-associated changes in chemosensory perception that have the potential to interact with dietary selection and nutrition in the elderly. A better understanding of these phenomena may promote health and well-being in the elderly.
The protooncogene c-sea encodes a transmembrane protein-tyrosine kinase related to the Met/hepatocyte growth factor/scatter factor receptor. (1993)

c-sea is the cellular homologue of the avian erythroblastosis virus S13-encoded oncogene v-sea. We have isolated and determined the nucleotide sequence of overlapping chicken cDNAs that encode the putative c-sea protooncogene product. The predicted reading frame encoded a 1404-aa polypeptide that had the structure of a receptor-like protein-tyrosine kinase and exhibited the highest degree of sequence similarity with the Met/hepatocyte growth factor/scatter factor receptor. Analysis of steady-state RNA expression revealed that c-sea mRNA levels were elevated approximately 5-fold in chicken embryo cells transformed by activated variants of the src nonreceptor protein-tyrosine kinase gene but not in cells transformed by the nuclear oncogenes v-myc or v-rel. A survey of c-sea expression in a variety of chicken tissues indicated that the highest levels of mRNA were located in peripheral white blood cell populations and in the intestine.
Position-Location Solutions by Taylor-Series Estimation (1976)

Taylor-series estimation gives a least-sum-squared-error solution to a set of simultaneous linearized algebraic equations. This method is useful in solving multimeasurement mixed-mode position-location problems typical of many navigational applications. While convergence is not proved, examples show that most problems do converge to the correct solution from reasonable initial guesses. The method also provides the statistical spread of the solution errors.