gebhart/patrepeval huggingface dataset:
Targeted Derepression of the Human Immunodeficiency Virus Type 1 Long Terminal Repeat by Pyrrole-Imidazole Polyamides (2002)

The host factor LSF represses the human immunodeficiency virus type 1 long terminal repeat (LTR) by mediating recruitment of histone deacetylase. We show that pyrrole-imidazole polyamides targeted to the LTR can specifically block LSF binding both in vitro and within cells via direct access to chromatin, resulting in increased LTR expression.
Platelet-derived growth factor stimulates non-mitochondrial Ca2+ uptake and inhibits mitogen-induced Ca2+ signaling in Swiss 3T3 fibroblasts. (1990)

Changes in intracellular free Ca2+ concentration [( Ca2+]i) were used to study the interaction between mitogens in Swiss 3T3 fibroblasts. Platelet-derived growth factor (PDGF) produced an increase in [Ca2+]i and markedly decreased the increases in [Ca2+]i caused by subsequent addition of bradykinin and vasopressin. If the order of the additions was reversed the [Ca2+]i response to PDGF was not inhibited by bradykinin or vasopressin. Inhibition of protein kinase C by staurosporine or chronic treatment of the cells with phorbol 12-myristate 13-acetate prevented the inhibitory effect of PDGF on the [Ca2+]i response to vasopressin but not bradykinin. PDGF did not decrease the receptor binding of bradykinin and produced only a small decrease in the receptor binding of vasopressin. PDGF decreased the rise in [Ca2+]i caused by the Ca2+ ionophores 4-bromo-A23187 and ionomycin and by a membrane perturbing ether lipid, 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine, both in the presence and absence of external Ca2+. There was no change in cell 45Ca2+ influx caused by PDGF, vasopressin, or bradykinin. 45Ca2+ efflux from cells exposed to PDGF and vasopressin mirrored the changes in [Ca2+]i caused by the agents, that is, PDGF added after vasopressin produced a further increase in 45Ca2+ efflux but vasopressin did not increase 45Ca2+ efflux after PDGF. PDGF but not vasopressin caused an increase in the uptake of 45Ca2+ into an inositol 1,4,5-trisphosphate-insensitive non-mitochondrial store in permeabilized cells. The results suggest that the decreased [Ca2+]i response to mitogens after PDGF represents an action of PDGF at a point beyond the release of intracellular Ca2+ and the influx of external Ca2+, caused by an increase in the rate of removal of cytoplasmic free Ca2+. This increased removal of cytoplasmic Ca2+ by PDGF is not due to the increased export of Ca2+ from the cell but results from increased Ca2+ uptake into non-mitochondrial stores.
Phase retrieval and twin-image elimination for in-line Fresnel holograms (1987)

Fourier phase-retrieval algorithms are modified and applied to in-line holography, where phase is lost during the hologram recording process. Retrieval of phase permits separation of real-object distributions from the twin-image interference that accompanies conventional optical reconstruction. The rate of convergence is enhanced by the availability of a good initial guess based on the digital equivalent of conventional optical reconstruction.
Endothelial nitric oxide synthase: molecular cloning and characterization of a distinct constitutive enzyme isoform. (1992)

Nitric oxide (NO) is a ubiquitous intercellular messenger molecule synthesized from the amino acid L-arginine by NO synthases in diverse cells and tissues. NO is synthesized in vascular endothelial cells and appears to play an important role in the control of blood pressure and platelet aggregation. A detailed understanding of the regulation of NO synthesis by endothelial cells has been hampered by the lack of molecular clones for endothelial NO synthase; the isolation and characterization of such clones is reported herein. The constitutive NO synthases present in endothelial cells and in brain share common biochemical and pharmacologic features. We purified NO synthase from bovine brain and determined the amino acid sequence of several tryptic peptides. The sequence of the bovine brain peptides is nearly identical to the deduced amino acid sequence previously determined for the rat brain NO synthase. These sequence data were utilized to design PCR-generated NO synthase cDNA probes, which were used to isolate clones encoding NO synthase from a bovine aortic endothelial cell (BAEC) cDNA library. A full-length NO synthase cDNA clone was isolated, representing a protein of 1205 amino acids with a molecular mass of 133 kDa; transfection of this clone in a heterologous expression system demonstrated the expected enzymatic activity. The deduced amino acid sequence of the BAEC NO synthase cDNA differs at numerous residues from the sequence determined for the purified bovine brain protein and shows 50-60% sequence identity with recently isolated molecular clones for murine macrophage and rat brain NO synthase isoforms. Bovine genomic Southern blots probed with bovine brain and BAEC NO synthase cDNA probes identify distinct bands, indicating that these cDNAs are the products of different genes. Prolonged treatment of BAECs with the cytokine tumor necrosis factor alpha, which we have previously shown to result in a marked increase in NO synthase activity, is associated with a decrease in the abundance of the 4.8-kilobase BAEC NO synthase transcript. The increase in BAEC NO synthase activity induced by tumor necrosis factor alpha is thus likely to involve posttranscriptional mechanisms or the induction of a distinct endothelial NO synthase isoform.
Properties of SEPT9 isoforms and the requirement for GTP binding (2004)

Members of the evolutionarily conserved septin family of genes are emerging as key components of several cellular processes including membrane trafficking, cytokinesis, and cell-cycle control events. SEPT9 has been shown to have a complex genomic architecture, such that up to 15 different isoforms are possible by the shuffling of five alternate amino termini and three alternate carboxy termini. Genomic and transcriptional alterations of SEPT9 have been associated with neoplasia. The present study has used a Sept9-specific antibody to determine the pattern of isoform expression in a range of tumour cell lines. Western blot analysis indicated considerable variation in the relative amounts and isoform content of Sept9. Immunofluorescence studies showed a range of patterns of cytoplasmic localization ranging from mainly particulate to mainly filamentous. Expression constructs were also generated for each amino terminal isoform to investigate the patterns of localization of individual isoforms and the effects on cells of ectopic expression. The present study shows that the epsilon isoform appears filamentous in this overexpression system while the remaining isoforms are particulate and cytoplasmic. Transient transfection of individual constructs into tumour cell lines results in cell-cycle perturbation with a G2/M arrest and dramatic growth suppression, which was greatest in cell lines with the lowest amounts of endogenous Sept9. Similar phenotypic observations were made with GTP-binding mutants of all five N-terminal variants of Sept9. However, dramatic differences were observed in the kinetics of accumulation of wild-type versus mutant septin protein in transfected cells. In conclusion, the present study shows that the expression patterns of Sept9 protein are very varied in a panel of tumour cell lines and the functional studies are consistent with a model of septin function as a component of a molecular scaffold that contributes to diverse cellular functions. Alterations in the levels of Sept9 protein by overexpression of individual isoforms can clearly perturb cellular behaviour and may thus provide a mechanistic explanation for observations of deranged septin expression in neoplasia.
Recombinant human nerve growth factor in the treatment of diabetic polyneuropathy (1998)

Recombinant human nerve growth factor appears to be safe and shows preliminary evidence of efficacy in patients with symptomatic diabetic polyneuropathy.
Amyotrophic lateral sclerosis: a consensus viewpoint on designing and implementing a clinical trial (2004)

In November 2002, an advisory board meeting was convened by Novartis Pharma to provide recommendations and rationale for clinical trials designed to evaluate new treatments, such as TCH346, for amyotrophic lateral sclerosis (ALS). In terms of selecting appropriate outcome measures, the panel recommended the use of the ALS Functional Rating Scale (ALSFRS-R) to measure primary endpoints. A review of other key issues in this area including regional variations in the epidemiology, diagnosis and management of ALS, defining patient populations and doses of trial medication, and accommodating the likelihood of co-medication with pre-existing treatment in trial design, are discussed.
Making use of hypertext links when retrieving information (1993)

Hypermedia links were invented to support the manual browsing through large hypertext or hypermedia collections.
Elevated Plasma Levels of Antimicrobial Polypeptides in Patients with Severe Sepsis (2010)

We wanted to investigate if plasma levels of antimicrobial polypeptides (AMPs) are increased in severe sepsis and if they correlate with severity and mortality. Samples were collected from 31 sepsis patients at the intensive care unit. The Sequential Organ Failure Assessment (SOFA) score and 90-day mortality were registered, and inflammatory markers and AMP levels were measured by ELISA. A median SOFA score (13) and cardiovascular SOFA score (3) indicated multiorgan failure with severe circulatory derangement, and elevated cytokine levels indicated inflammatory activation. Levels of bactericidal/permeability-increasing protein, heparin-binding protein, alpha-defensins and lactoferrin but not LL-37 were elevated in sepsis patients compared with controls. Bactericidal/permeability-increasing protein levels correlated with mortality, with lower levels in survivors. Levels of all AMPs, except LL-37, positively correlated with the cardiovascular SOFA score. In conclusion, levels of several AMPs are increased in sepsis and correlate with circulatory derangement. This probably reflects neutrophil activation as part of an innate immune response.
All-Inorganic Field Effect Transistors Fabricated by Printing (1999)

A solution of cadmium selenide nanocrystals was used to print inorganic thin-film transistors with field effect mobilities up to 1 square centimeter per volt second. This mobility is an order of magnitude larger than those reported for printed organic transistors. A field effect was achieved by developing a synthesis that yielded discretely sized nanocrystals less than 2 nanometers in size, which were free of intimately bound organic capping groups. The resulting nanocrystal solution exhibited low-temperature grain growth, which formed single crystal areas encompassing hundreds of nanocrystals. This process suggests a route to inexpensive, all-printed, high-quality inorganic logic on plastic substrates.
Tandem repeats finder: a program to analyze DNA sequences (1999)

A tandem repeat in DNA is two or more contiguous, approximate copies of a pattern of nucleotides. Tandem repeats have been shown to cause human disease, may play a variety of regulatory and evolutionary roles and are important laboratory and analytic tools. Extensive knowledge about pattern size, copy number, mutational history, etc. for tandem repeats has been limited by the inability to easily detect them in genomic sequence data. In this paper, we present a new algorithm for finding tandem repeats which works without the need to specify either the pattern or pattern size. We model tandem repeats by percent identity and frequency of indels between adjacent pattern copies and use statistically based recognition criteria. We demonstrate the algorithm's speed and its ability to detect tandem repeats that have undergone extensive mutational change by analyzing four sequences: the human frataxin gene, the human beta T cellreceptor locus sequence and two yeast chromosomes. These sequences range in size from 3 kb up to 700 kb. A World Wide Web server interface atc3.biomath.mssm.edu/trf.html has been established for automated use of the program.
Predicting Viscosity of Limestone–Water Slurry (2009)

The rheological behavior of limestone-water slurry samples was investigated for different volume concentrations, particle size distribution and slurry temperature. Experiments were conducted over a range of volumetric solids concentration ( = 0.20 -0.46) in shear rate range of 1-300 s -1 . The slurry showed Newtonian behavior up to a volumetric solids concentration of 37.8 vol. %, beyond which the slurry was highly pseudoplastic in nature and fitted excellently to a non-Newtonian Power law model. The relative viscosity ( r ) of the mixture slurry, defined as the suspension viscosity over the viscosity of the suspending medium was found to be increasing exponentially when exceeds 0.404. By adopting an experimental approach, the rheological data indicated that might reach 0.462. Using the ( 2 1 1 -r ) - relationship proposed by Liu, the theoretical maximum solids fraction ( m ) was evaluated as m = 0.504 for the given slurry samples and was then used to predict the relative viscosity ( r ) by some existing models. Five empirical models namely; Liu, Dabak et al., Krieger-Dougherty, Mooney and Chong et al. were considered for the purpose. Liu's model better predicted the relative viscosity and thus would be helpful in evaluating the hydraulic parameters accurately for design of limestone slurry pipelines operating at high concentrations.
Hepoxilins sensitize blood vessels to noradrenaline—stereospecificity of action (1992)

1. The vascular activity of two stereoisomers of hepoxilin A3 (HxA3) (8R and 8S) and of its glutathione conjugate, hepoxilin A3-C (HxA3-C) (8R and 8S), was investigated on rat helicoidal strips of thoracic aorta and longitudinal strips of portal vein. 2. Neither of the hepoxilins tested had a direct effect on the tone of the aortic strip or on the spontaneous contractions of the portal vein. However, the noradrenaline (NA)-induced response of these vessels, as expressed by the dose required for half maximal contraction, (EC50) was greater in HxA3 (8S)- and HxA3-C (8R)-treated aorta. Increased frequency and strength of spontaneous contractions of the portal vein were detected at lower concentrations of NA in the presence of hepoxilins. 3. The threshold dose for both hepoxilins was 10(-8) M and their effect was not dose-related beyond 10(-8) M. The effect of hepoxilin appeared after a 45 min incubation period and could be observed even if the compounds were washed out after 15 min. 4. Stereochemical specificity was observed. The 8S isomer of HxA3 was active in potentiating the NA-induced contraction of these vessels while the 8R isomer was inactive. In contrast, the 8R isomer of HxA3-C was active while the 8S isomer was inactive. In both tissues, HxA3 (8S) was more potent than its glutathione conjugate, HxA3-C (8R). 5. In calcium-free buffer or in the presence of a calcium channel blocker (nifedipine 1 microM), no potentiation of NA-induced contraction by hepoxilins could be observed, suggesting the involvement of extracellular calcium in the actions of hepoxilins.6. These experiments suggest that hepoxilins may be involved in the modulation of vascular tone and contractility.
Unregulated Expression of the Erythropoietin Receptor Gene Caused by Insertion of Spleen Focus-Forming Virus Long Terminal Repeat in a Murine Erythroleukemia Cell Line (1991)

A murine erythroleukemia (MEL) cell line, F5-5, expressed 10,000 binding sites for erythropoietin (EPO) per cell, 10-fold more than was expressed by other murine erythroleukemia cell lines and normal erythroid progenitors. Northern (RNA) and Southern blot analyses revealed overexpression of mRNA for the EPO receptor (EPOR) and rearrangement of one of the EPOR gene alleles in F5-5 cells, respectively. Molecular cloning of F5-5-derived cDNA encoding EPOR revealed that the 5' noncoding region of the EPOR cDNA corresponds to the 3' long terminal repeat sequence of the polycythemic strain of Friend spleen focus-forming virus (F-SFFVP). The aberrant EPOR transcripts containing the 3' long terminal repeat sequence were mainly expressed in F5-5 cells. The same integration upstream of the EPOR gene was also observed in other subclones and the parent cell line. It is possible that overexpression of EPOR by viral promoter insertion will confer growth advantage to an F-SFFVP-infected erythroid progenitor cell, leading to positive clonal selection through further leukemogenic steps.
Comment on `Non-equilibrium thermodynamics of light absorption' (2000)

A recent paper by Meszna and Westerhoff (1999 J. Phys. A: Math. Gen. 32 301) has aimed to address what is referred to as a principal question of biological thermodynamics, the possibility of describing photosynthesis in terms of non-equilibrium thermodynamics. The issue is associated with a misrepresentation of the fundamental photophysics involved, and as a result the analysis is invalid.
Laser capture microdissection analysis of gene expression in macrophages from atherosclerotic lesions of apolipoprotein E-deficient mice (2002)

Macrophage foam cells are integral in the development of atherosclerotic lesions. Gene expression analysis of lesional macrophage foam cells is complicated by the cellular heterogeneity of atherosclerotic plaque and the presence of lesions of various degrees of severity. To overcome these limitations, we tested the ability of laser capture microdissection (LCM) and real-time quantitative reverse transcription PCR to selectively analyze RNA from lesional macrophages of apolipoprotein E (apoE)-deficient mice. Proximal aortic tissue sections were immunostained for macrophagespecific CD68/macrosialin by a rapid (approximately 15-min) protocol. Alternating sections from each animal were used to isolate RNA either from entire sections (analogous to isolation from whole tissue) or by LCM selection of CD68-positive cells. We measured the mRNA levels of CD68, a macrophage-specific marker, alpha-actin, a smooth muscle cell marker, and cyclophilin A, a control gene. Compared with whole sections, CD68 mRNA levels were greatly enriched (33.6-fold) in the laser-captured lesional macrophages. In contrast to whole sections, LCM-derived RNA had undetectable levels of alpha-actin. To illustrate the ability of this method to measure changes in lesional macrophage gene expression, we injected 100 microg of lipopolysaccharide i.p. into apoE-deficient mice and detected in laser-captured lesional macrophages increased mRNA expression for vascular cell adhesion molecule-1, intercellular cell adhesion molecule-1, and monocyte chemoattractant protein-1 (11.9-, 32.5-, and 31.0-fold, respectively). By selectively enriching foam cell RNA, LCM provides a powerful approach to study the in situ expression and regulation of atherosclerosis-related genes. This approach will allow the study of macrophage gene expression under various conditions of plaque formation, regression, and response to genetic and environmental perturbations.
M. bovis-BCG elicits memory CD8+ T cell responses to mycobacteria in cattle (43.53) (2007)

Abstract Tuberculosis (TB) remains one of the leading causes of death due to infectious disease. Current aims to improve vaccines against TB have focused on enhancing immunity conferred by the attenuated M. bovis BCG (BCG) vaccine. The design of a vaccine to specifically boost the protective features of BCG requires a greater understanding of the immune response induced by BCG vaccination. In this work we show that vaccination with BCG induces a population of CD8+CD45RO+ T cells that proliferate, produce IFN-gamma, up-regulate expression of perforin and granulysin, and lyse BCG-infected macrophages, following antigen specific stimulation. To determine whether a similar response could be detected in vivo, vaccinated animals were re-inoculated intradermally with BCG or PBS eight weeks after primary BCG vaccination. Draining lymph nodes were removed 3 days after the second inoculation for analysis by immunofluorescence and confocal microscopy for the presence of activated CD8+ T cells. Clusters of CD8+CD3+perforin+ cells were readily detectable in lymph nodes from animals re-inoculated with BCG but absent in the animals given PBS in the second inoculum. These results suggest that the memory CD8+ T cells induced by BCG vaccination have the capacity to mount secondary responses to mycobacteria in vivo. Support for these studies was provided by the BBSRC, DEFRA and the Jenner Institute.
COSMOS: the COsmic-ray Soil Moisture Observing System (2012)

Abstract. The newly-developed cosmic-ray method for measuring area-average soil moisture at the hectometer horizontal scale is being implemented in the COsmic-ray Soil Moisture Observing System (or the COSMOS). The stationary cosmic-ray soil moisture probe measures the neutrons that are generated by cosmic rays within air and soil and other materials, moderated by mainly hydrogen atoms located primarily in soil water, and emitted to the atmosphere where they mix instantaneously at a scale of hundreds of meters and whose density is inversely correlated with soil moisture. The COSMOS has already deployed more than 50 of the eventual 500 cosmic-ray probes, distributed mainly in the USA, each generating a time series of average soil moisture over its horizontal footprint, with similar networks coming into existence around the world. This paper is written to serve a community need to better understand this novel method and the COSMOS project. We describe the cosmic-ray soil moisture measurement method, the instrument and its calibration, the design, data processing and dissemination used in the COSMOS project, and give example time series of soil moisture obtained from COSMOS probes.
In vitro characterization of the yeast mitochondrial promoter using single-base substitution mutants. (1987)

A short DNA sequence, 5'ATATAAGTA(+1)3', extending from -8 to +1 nucleotides has been shown to function as a promoter in the yeast mitochondrial genome. A complete set of single site mutations of this nonanucleotide promoter sequence has been constructed, cloned, and used to promote specific in vitro transcription using a highly purified mitochondrial RNA polymerase. Each deviation from the natural promoter sequence results in a reduction or abolition of specific transcription depending on the nucleotide substituent. The nucleotide at -8 is not considered as a component of the promoter. Any nucleotide at position +1 is compatible with correct transcriptional initiation. The consensus sequence that exists in vivo is the strongest promoter since only down mutations are seen among the substitutions. The mutant analyses indicate that a very short octanucleotide sequence comprised of 5'TAT/aAA/g/cGT/a/cN(+1)3' is the minimal sequence necessary to direct accurate initiation by mitochondrial RNA polymerase.
Role of Protein A in the Evasion of Host Adaptive Immune Responses by Staphylococcus aureus (2013)

Staphylococcus aureus causes recurrent skin and bloodstream infections without eliciting immunity. Heritable defects in neutrophil and T cell function, but not B cell or antibody development, are associated with increased incidence of S. aureus infection, and efforts to develop antibody-based S. aureus vaccines have thus far been unsuccessful. We show here that the Fcγ and VH3-type Fab binding activities of staphylococcal protein A (SpA) are essential for S. aureus escape from host immune surveillance in mice. The virulence attributes of SpA in mice required mature B cells and immunoglobulin. These results suggest that antibodies and B cells play a key role in the pathogenesis of staphylococcal infections and provide insights into the development of a vaccine against S. aureus.