gebhart/patrepeval huggingface dataset:
Genetic and Antigenic Variation in Type 3 Polioviruses: Characterization of Strains by Monoclonal Antibodies and T1 Oligonucleotide Mapping (1982)

Considerable genetic and antigenic heterogeneity was detected among a collection of 17 poliovirus type 3 strains isolated between 1939 and 1958 in studies using monoclonal antibodies and by T1 oligonucleotide mapping. Heterogeneity was detected even amongst a collection of nine viruses designated Saukett and assumed to originate from the same prototype virus. The monoclonal antibodies were found to differ in their strain specificities for poliovirus type 3 strains in virus neutralization or single-radial-immunodiffusion tests. Relationships between strains detected in this way were in general consistent with those detected by oligonucleotide mapping. One of the monoclonal antibodies (NIBp 56) was able to distinguish between certain Saukett virus strains which differed by as little as a single specific oligonucleotide. The heterogeneity detected amongst Saukett viruses is of potential practical importance since these strains are used widely in the manufacture of inactivated poliovirus vaccine.
Quantitative Imaging of Lateral ErbB1 Receptor Signal Propagation in the Plasma Membrane (2000)

Evidence for a new signaling mechanism consisting of ligand-independent lateral propagation of receptor activation in the plasma membrane is presented. We visualized the phosphorylation of green fluorescent protein (GFP)-tagged ErbB1 (ErbB1-GFP) receptors in cells focally stimulated with epidermal growth factor (EGF) covalently attached to beads. This was achieved by quantitative imaging of protein reaction states in cells by fluorescence resonance energy transfer (FRET) with global analysis of fluorescence lifetime imaging microscopy (FLIM) data. The rapid and extensive propagation of receptor phosphorylation over the entire cell after focal stimulation demonstrates a signaling wave at the plasma membrane resulting in full activation of all receptors.
Influence of MUC18/MCAM/CD146 expression on human melanoma growth and metastasis in SCID mice (1999)

The cell surface glycoprotein MUC18MCAM/CD146 was originally defined as a marker of melanoma progression and has been suspected to be directly linked to the metastatic process of this malignancy. In order to address this question, 2 MCAM negative human melanoma cell lines, SK-2 and XP44RO(Mel), were transfected with MCAM-encoding cDNA. Surface MCAM expression on SK-2 and XP44RO(Mel) transfectants was similar to that observed in naturally occurring MCAM positive human melanoma cells and transfectants demonstrated MCAM-dependent increase in homotypic adhesion in vitro. The growth behavior of 7 MCAM transfectants and their respective vector controls was evaluated in SCID mice. Tumor size at 4-5 weeks after s.c. implantation was highly variable, but did not correlate with MCAM expression. Despite massive primary tumor formation at the injection site, no spontaneous metastasis was observed with any of the investigated MCAM transfectants. The influence of MCAM expression on lung metastases formation in an experimental metastasis assay was system dependent, converting only XP44RO(Mel) transfectants into metastatic cells, although increased homotypic adhesion, leading to formation of tumor cell clusters, was observed with transfectants of both cell lines in vitro. Our findings indicate that MCAM expression of human melanoma cells has an influence on later stages of the metastatic process only, namely, extravasation and establishment of new foci of growth, but is per se not sufficient for this process.
CEEFAX: A Proposed New Broadcasting Service (1974)

Field trials are being completed of a BBC system which can transmit a “magazine” of 32 “pages” of text for display on a home TV screen. The information is conveyed in digital form using the ASCII 7-bit code. In the 625-line 50-field television system the data signal is inserted on lines 17 and 18 together with the corresponding lines (330 and 331) in the alternate field and the bit rate of 4.5 Mb/s during the transmission of the signal leads to an average bit rate of 23.4 kb/s. The complete magazine is sent in 15.36 s. Special CEEFAX TV receivers or adapters for use will ordinary sets decode the signals and store the data for the page selected by the user: the store is read every field via character-generating circuits which provide the video signals to form the alphanumeric display. Weather forecasts, news items, and subtitles are among the subjects suitable for CEEFAX which could also be adapted to take library reference material, bank statements, etc. from the telephone line or a shelf-full of books from a single video disc. A Technical Study Group is examining this system, a comparable one developed by the Independent Broadcasting Authority, and proposals from British industry, and will recommend characteristics for a single data broadcasting service.
Involvement of Arginine 120, Glutamate 524, and Tyrosine 355 in the Binding of Arachidonate and 2-Phenylpropionic Acid Inhibitors to the Cyclooxygenase Active Site of Ovine Prostaglandin Endoperoxide H Synthase-1 (1996)

Examination of the crystal structure of the ovine prostaglandin endoperoxide synthase-1 (PGHS-1)/S- flurbiprofen complex (Picot, D., Loll, P.J., and Garavito, R.M. (1994) Nature 367, 243-2491) suggests (a) that the carboxyl group of arachidonic acid interacts with the arginino group of Arg120; (b) that Arg120 forms an important salt bridge with Glu524; and (c) that Tyr355, which is in close proximity to Arg120, could determine the stereochemical specificity of PGHS-1 toward 2-phenylpropionic acid inhibitors. To test these concepts, we used site-directed mutagenesis to prepare ovine PGHS-1 mutants having modifications of Arg120 (R120K, R120Q, R120E), Glu524 (E524D, E524Q, E524K), and Tyr355 (Y355F) and examined the properties of the mutant enzymes expressed in COS-1 cells. All of the mutants retained at least part of their cyclooxygenase and peroxidase activities except the R120E mutant, which had no detectable activity. The Km values of the R120K and R120Q mutants with arachidonic acid were 87 and 3300 microM, respectively, versus 4 microM for native PGHS-1. The R120Q mutant failed to undergo suicide inactivation during catalysis or time-dependent inhibition by flurbiprofen. These results are consistent with Arg120 binding the carboxylate group of arachidonate and suggest that interaction of the carboxylate group of substrates and inhibitors with Arg120 is necessary for suicide inactivation and time-dependent inhibition, respectively. The Km values for the E524D, E524Q, and E524K mutants were not significantly different from values obtained for the native PGHS-1, suggesting that this residue is not importantly involved in catalysis or substrate binding. The effect of modifications of Arg120 and Tyr355 on the stereospecificity of inhibitor binding was determined. Ratios of IC50 values for cyclooxygenase inhibition by D- and L-ibuprofen, a competitive cyclooxygenase inhibitor, were 32, 67, and 7.1 for native PGHS-1, R120Q PGHS-1, and Y355F PGHS-1, respectively. The decreased stereochemical specificity observed with the Y355F PGHS-1 mutant suggests that Tyr355 is a determinant of the stereospecificity of PGHS-1 toward inhibitors of the 2-phenylpropionic acid class.
Amino acid regulation of gene expression (2000)

The impact of nutrients on gene expression in mammals has become an important area of research. Nevertheless, the current understanding of the amino acid-dependent control of gene expression is limited. Because amino acids have multiple and important functions, their homoeostasis has to be finely maintained. However, amino-acidaemia can be affected by certain nutritional conditions or various forms of stress. It follows that mammals have to adjust several of their physiological functions involved in the adaptation to amino acid availability by regulating the expression of numerous genes. The aim of the present review is to examine the role of amino acids in regulating mammalian gene expression and protein turnover. It has been reported that some genes involved in the control of growth or amino acid metabolism are regulated by amino acid availability. For instance, limitation of several amino acids greatly increases the expression of the genes encoding insulin-like growth factor binding protein-1, CHOP (C/EBP homologous protein, where C/EBP is CCAAT/enhancer binding protein) and asparagine synthetase. Elevated mRNA levels result from both an increase in the rate of transcription and an increase in mRNA stability. Several observations suggest that the amino acid regulation of gene expression observed in mammalian cells and the general control process described in yeast share common features. Moreover, amino acid response elements have been characterized in the promoters of the CHOP and asparagine synthetase genes. Taken together, the results discussed in the present review demonstrate that amino acids, by themselves, can, in concert with hormones, play an important role in the control of gene expression.
<title>Trial of PACS employing magneto-optical disks</title> (1990)

Rewritable and compact media of magneto-optical disk (MOD) was firstly employed by us to store medical images such as digital X-ray films. The purpose is to test functions of communication media or circulating media as well as of filing media. Another feature of our trial system is to involve voice recording module for diagnostic reports. Method of clinical application and development approach of our PACS with MOD is discribed in this paper. Technology assessment of our system is also briefly descussed in terms of cost-effectiveness and security problem.
Design of a 10-bit 100 MSamples/s BiCMOS D/A converter (2002)

A 10-bit 100 MSamples/s current-steering D/A converter (DAC) has been designed and processed in a 0.8 /spl mu/m BiCMOS process. The DAC is intended for applications using direct digital synthesis, and focus has been set on achieving a high spurious free dynamic range (SFDR). The main part of the DAC is a matrix of current cells. To reduce skew between the steering signals to the current cells, an emitter-coupled logic (ECL) flip-flop, clocked by a global ECL clock, is included in each current cell. A bipolar differential pair, steered by the differential output of the ECL flip-flop, is used in each current cell to steer the current. At a generated frequency of f/sub g//spl ap/0.3/spl middot/f/sub s/ (f/sub s/=100 MSamples/s), the simulated SFDR is larger than 60 dB. The DAC operates at 5 V, and has a power consumption of approximately 650 mW. The area of the chip-core is 2.2 mm/spl times/2.2 mm. Furthermore a measure to estimate the SFDR for the DAC based on short term simulations is presented. This measure seems to correspond very well with SFDR for long term simulations.
Amino Acid Sequence Analysis, Gene Construction, Cloning, and Expression of Gelonin, a Toxin Derived from Gelonium multiflorum (1995)

The plant toxin gelonin is an extremely potent inhibitor of protein synthesis, similar in action to ricin. The mature protein primary sequence was obtained using conventional sequencing techniques. Gelonin was found to be composed of 258 amino acids and contains 21 lysine residues. This toxin shares approximately 33% sequence homology with trichosanthin and ricin A chain. A 774 bp synthetic gene encoding gelonin was synthesized and expressed in E. coli. Recombinant gelonin (approximately 28 kD) expression was monitored and demonstrated by western analysis. Purification and functional activity studies demonstrated that this protein behaves identically to that of the natural product. Recombinant gelonin (RG) thus joins a growing list of recombinant toxins currently available for use in the construction of recombinant immunotoxins composed of gelonin fused to binding domains of antibodies, growth factors, or other cytokines.
Simian T cell leukaemia virus type I subtype B in a wild-caught gorilla (Gorilla gorilla gorilla) and chimpanzee (Pan troglodytes vellerosus) from Cameroon (2004)

A serological survey for human T cell leukaemia virus (HTLV)/simian T cell leukaemia virus (STLV) antibodies was performed in 61 wild-caught African apes, including five gorillas and 56 chimpanzees originating from south Cameroon. Two young animals, a gorilla (Gorilla gorilla gorilla) and a chimpanzee (Pan troglodytes vellerosus), exhibited a pattern of complete HTLV-I seroreactivity. Sequence comparison and phylogenetic analyses using the complete LTR (750 bp) and a 522 bp fragment of the env gene indicated the existence of two novel STLV-I strains, both of which belonged to HTLV-I/STLV-I molecular clade subtype B, specific to central Africa. These first STLV-I strains to be characterized in gorilla and chimpanzee were closely related to each other as well as to several HTLV-I strains originating from inhabitants of south Cameroon, including pygmies. Such findings reinforce the hypothesis of interspecies transmission of STLV-I to humans, leading to the present day distribution of HTLV-I in central African inhabitants.
Adenovirus encoded cyclic nucleotide‐gated channels: a new methodology for monitoring cAMP in living cells (2001)

The current, static methodologies for measuring cyclic AMP (cAMP) may underestimate its regulatory properties. Here, we have exploited the Ca2+-conducting properties of cyclic nucleotide-gated (CNG) channels to measure cAMP in live cells, in response to various stimuli. We placed a mutated CNG channel with high sensitivity to cAMP in adenovirus to maximize and render facile its expression in numerous cell types. The ready, continuous nature of the readout contrasted with the traditional approach, which yielded similar static information, but lacked any continuous or interactive qualities. It seems fair to predict that this readily adopted approach will broaden the perception of cAMP signaling.
Bootstrap Methods and their Application (1997)

Bootstrap methods are computer-intensive methods of statistical analysis, which use simulation to calculate standard errors, confidence intervals, and significance tests. The methods apply for any level of modelling, and so can be used for fully parametric, semiparametric, and completely nonparametric analysis. This 1997 book gives a broad and up-to-date coverage of bootstrap methods, with numerous applied examples, developed in a coherent way with the necessary theoretical basis. Applications include stratified data; finite populations; censored and missing data; linear, nonlinear, and smooth regression models; classification; time series and spatial problems. Special features of the book include: extensive discussion of significance tests and confidence intervals; material on various diagnostic methods; and methods for efficient computation, including improved Monte Carlo simulation. Each chapter includes both practical and theoretical exercises. S-Plus programs for implementing the methods described in the text are available from the supporting website.
Anti-inflammatory therapy ameliorates leukocyte adhesion and microvascular flow abnormalities in transgenic sickle mice (2004)

In sickle cell disease, inflammatory activation of vascular endothelium and increased leukocyte-endothelium interaction may play an important role in the occurrence of vasoocclusion. In sickle mouse models, inflammatory stimuli (e.g., hypoxia-reoxygenation and cytokines) result in increased leukocyte recruitment and can initiate vasoocclusion, suggesting that anti-inflammatory therapy could be beneficial in management of this disease. We have tested the hypothesis that inhibition of endothelial activation in a transgenic mouse model by anti-inflammatory agents would lead to reduced leukocyte recruitment and improved microvascular blood flow in vivo. In transgenic sickle mice, hypoxia-reoxygenation resulted in greater endothelial oxidant production than in control mice. This exaggerated inflammatory response in transgenic mice, characterized by increased leukocyte recruitment and microvascular flow abnormalities, was significantly attenuated by antioxidants (allopurinol, SOD, and catalase). In contrast, control mice exhibited a muted response to antioxidant treatment. In addition, hypoxia-reoxygenation induced activation of NF-kappaB in transgenic sickle mice but not in control mice. In transgenic sickle mice, sulfasalazine, an inhibitor of NF-kappaB activation and endothelial activation, attenuated endothelial oxidant generation, as well as NF-kappaB activation, accompanied by a marked decrease in leukocyte adhesion and improved microvascular blood flow. Thus targeting oxidant generation and/or NF-kappaB activation may constitute promising therapeutic approaches in sickle cell disease.
Catheter Ablation of Cardiac Autonomic Nerves for Prevention of Vagal Atrial Fibrillation (2000)

-Transvascular atrial parasympathetic nerve system modification by RFCA abolishes vagally mediated AF. This antifibrillatory procedure may provide a foundation for investigating the usefulness of neural ablation in chronic animal models of AF and eventually in patients with AF and high vagal tone.
Development and evaluation of selective, reversible LSD1 inhibitors derived from fragments (2013)

Two series of aminothiazoles have been developed as reversible inhibitors of lysine specific demethylase 1 (LSD1) through the expansion of a hit derived from a high concentration biochemical fragment based screen of 2466 compounds. The potency of the initial fragment hit was increased 32-fold through synthesis, with one series of compounds showing clear structure–activity relationships and inhibitory activities in the range of 7 to 187 μM in a biochemical assay. This series also showed selectivity against the related FAD-dependent enzyme mono-amine oxidase A (MAO-A). Although a wide range of irreversible inhibitors of LSD1 have been reported with activities in the low nanomolar range, this work represents one of the first reported examples of a reversible small molecule inhibitor of LSD1 with clear SAR and selectivity against MAO-A, and could provide a platform for the development of more potent reversible inhibitors. Herein, we also report the use of a recently developed cell-based assay for profiling LSD1 inhibitors, and present results on our own compounds as well as a selection of recently described reversible LSD1 inhibitors.
Driving scheme for stable operation of 2-TFT a-Si AMOLED pixel (2005)

The amorphous silicon (a-Si) thin film transistor (TFT) backplane is becoming the technology of choice for active matrix organic light emitting diode (AMOLED) displays in view of its industrial accessibility and low fabrication cost over large area. However, the a-Si TFT suffers from threshold voltage (VT) shift. Presented is the simplest voltage-programmed pixel with an ability to compensate for the VT-shift in the drive TFT of the AMOLED pixel circuit. Simulation results also show that the pixel circuit can tolerate the spatial mismatch, temperature variation, and mechanical stress.
Response to the RIF-1 tumor in vitro and in C3H/Km mice to X-radiation (cell survival, regrowth delay, and tumor control), chemotherapeutic agents, and activated macrophages. (1980)

The radiation response of logarithmic growth phase and fed plateau phase RIF-1 cells in vitro was found to be characterized by D0 (slope of cell survival curve on semilog plot) values of 110 and 133 rads and extrapolation numbers of 36 and 28, respectively. The response of the tumor in vivo to X-irradiation in nonanesthetized mice showed a dependence on the tumor implantation site. In the leg muscle, the response indicated that most cells were at an intermediate level of oxygenation, whereas in the subcutaneous tissue of the flank, the response of the tumor indicated that it had a small fraction (1.5%) of hypoxic cells of maximum radioresistance. Misonidazole radiosensitized the leg-implanted tumor as measured both by cell survival and regrowth delay. The median tumor cure dose of radiation in mice was 3,990 rads (3,670--4,340), which agreed closely with that predicted from the radiation survival curve. The tumor was relatively insensitive to a single dose of 1,3-bis(2-chloroethyl)-1-nitrosourea, sensitive to a single dose of cis-platinum, and highly sensitive to a single dose of cyclophosphamide.
The making of an expert. (2007)

Popular lore tells us that genius is born, not made. Scientific research, on the other hand, reveals that true expertise is mainly the product of years of intense practice and dedicated coaching. Ordinary practice is not enough: To reach elite levels of performance, you need to constantly push yourself beyond your abilities and comfort level. Such discipline is the key to becoming an expert in all domains, including management and leadership. Those are the conclusions reached by Ericsson, a professor of psychology at Florida State University; Prietula, a professor at the Goizueta Business School; and Cokely, a research fellow at the Max Planck Institute for Human Development, who together studied data on the behavior of experts, gathered by more than 100 scientists. What consistently distinguished elite surgeons, chess players, writers, athletes, pianists, and other experts was the habit of engaging in "deliberate" practice--a sustained focus on tasks that they couldn't do before. Experts continually analyzed what they did wrong, adjusted their techniques, and worked arduously to correct their errors. Even such traits as charisma can be developed using this technique. Working with a drama school, the authors created a set of acting exercises for managers that remarkably enhanced executives' powers of charm and persuasion. Through deliberate practice, leaders can improve their ability to win over their employees, their peers, or their board of directors. The journey to elite performance is not for the impatient or the faint of heart. It takes at least a decade and requires the guidance of an expert teacher to provide tough, often painful feedback. It also demands would-be experts to develop their "inner coach" and eventually drive their own progress.
Protein kinase C and T cell activation (1990)

Understanding the intracellular mechanisms by which binding of ligands, such as hormones and growth factors, to their specific receptors elicits the appropriate cellular response has long been a topic of great interest. Considerable excitement was generated when it was recognised that several receptor-ligand interactions operate via the hydrolysis of inositol phospholipids. This yields, at least, two 'second messengers', namely, inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], which causes the release of Ca2+ from intracellular stores, and 1,2-diacylglycerol (ac2Gro), which activates the serine/threonine-specific enzyme, protein kinase C(PKC), reviewed in [1] and [2]. The pertinent question that follows is, how do PKC activation and elevation of the intracellular Ca2+ concentration evoke cell responses? In this review, attention has been focused on PKC, and the consequences of its activation in resting human T cells. Evidence that PKC activity is, at least partially, responsible for activation of resting human T cells will be examined, and some of the more recent research investigating how PKC activation elicits this cell response will be described.