gebhart/patrepeval huggingface dataset:
Role of Molecular Ions, Metastable Molecules, and Resonance Radiation in the Breakdown of Rare Gases (1960)

Theoretical calculations are made of the rates of arrival of atomic and molecular ions, of atomic and molecular metastables, and of nonresonance and resonance radiation at the cathode of parallel plane electrodes during the buildup of current preceding the breakdown of a rare gas. The electron density is assumed to increase exponentially with time and distance. Previous analyses are extended to obtain the particle currents of molecular ions and of metastable atoms and molecules at the cathode. The Holstein-Biberman formulation of the transport equation for the density of atoms in the resonance state is solved numerically to find the fraction of resonance photons arriving at the cathode. The fraction of resonance radiation reaching the cathode varies with the growth constant of the electron current in very nearly the same manner as for delayed photons and varies much less rapidly with electrode spacing and gas density than for the case of diffusing particles. The theory is applied to the calculation of the growth constant as a function of applied voltage for helium at 100 mm Hg pressure and a 1-centimeter gap. The growth of current is found to be controlled by the rates of arrival of molecular metastables, molecular ions, and resonance radiation at the cathode.
Germ-line mutations in p27 Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans (2006)

MENX is a recessive multiple endocrine neoplasia-like syndrome in the rat. The tumor spectrum in MENX overlaps those of human multiple endocrine neoplasia (MEN) types 1 and 2. We mapped the MenX locus to the distal part of rat chromosome 4, excluding the homologs of the genes responsible for the MEN syndromes (RET and MEN1) and syndromes with an endocrine tumor component (VHL and NF1). We report the fine mapping of the disease locus and the identification of a homozygous frameshift mutation in Cdkn1b, encoding the cyclin-dependent kinase inhibitor p27(Kip1). As a consequence of the mutation, MENX-affected rats show dramatic reduction in p27(Kip1) protein. We have identified a germ-line nonsense mutation in the human CDKN1B gene in a MEN1 mutation-negative patient presenting with pituitary and parathyroid tumors. Expanded pedigree analysis shows that the mutation is associated with the development of an MEN1-like phenotype in multiple generations. Our findings demonstrate that germ-line mutations in p27(Kip1) can predispose to the development of multiple endocrine tumors in both rats and humans.
Achieving scalability in OLAP materialized view selection (2002)

The goal of on-line analytical processing (OLAP) is to quickly answer queries from large amounts of data residing in a data warehouse. Materialized view selection is an optimization problem encountered in OLAP systems. Published work on the problem of materialized view selection presents solutions scalable in the number of possible views. However, the number of possible views is exponential relative to the number of database dimensions. A truly scalable solution must be polynomial time relative to the number of dimensions. We present such a solution, our Polynomial Greedy Algorithm. Complexity analysis proves scalability, and a performance study verifies the result. Empirical evidence demonstrates benefits close to existing algorithms. We conclude the Polynomial Greedy Algorithm functions effectively where existing algorithms fail dramatically.
Portable Mapping of Uml Design Specifications into Object Oriented Code (2012)

This paper proposes a stand-alone software that accepts UML Design Specifications through a simple user interface. It will generate XML code and object-oriented code for the specifications provided by the user, in parallel. Along with the generation of code, the software will also produce the graphical representation of the UML diagram, thus facilitating the easy visualization of the diagram being produced. This tool will free the software developer from the mundane task of writing simple class skeleton so he/she can concentrate on the business logic and overall architecture of his/her project, provides consistency between design and code and eliminates the unintended errors that can creep into manually written code. It will create an effective integration between the design and implementation stages. Also, due to generation of XML code, it facilitates portability. This paper concentrates mainly on class diagram and Java code that can be extended in future to cover other diagrams and other object-oriented languages.
A 1/3-in 270000 pixel CCD image sensor (1991)

A 1/3-in interline transfer charge-coupled-device (CCD) image sensor with 270000 pixels has been developed. The effective sensing area of (4.8(H)*3.6(V)) mm/sup 2/ is adopted for the 1/3-in format. This sensor realizes 330 TV lines of color horizontal resolution. In addition, a new on-chip color filter is used, and a minimum object illuminance of 3 1x has been achieved. The electronic shutter was realized by developing the vertical-extraction method, with a wide range of shutter speed from 1/60 to 1/10000 s. Moreover, the use of an embedded photodiode makes it possible to achieve a low dark current. This feature, together with the 5-V drive, gives the sensor additional high performance, including low smear (0.01%).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Memory function in normal aging (2003)

Basic findings obtained on memory functions in normal aging are presented and discussed with respect to five separate but interacting memory systems. These systems are: episodic memory, semantic memory, short-term memory, perceptual representation system and procedural memory. All available evidence from cross-sectional research shows that there is a linear, decreasing memory performance as a function of age for episodic memory. Longitudinal studies suggest, however, that this age deficit may be an overestimation, by showing a relatively stable performance level up to middle age, followed by a sharp decline. Studies on semantic memory, short-term memory, perceptual representation system, and procedural memory show a relatively constant performance level across the adult life span, although some tasks used to assess short-term memory and procedural memory have revealed an age deficit. Disregarding the mixed results for these latter two memory systems, it can be concluded that episodic memory is unique in showing an age deficit. Episodic memory is also unique in the sense that it is the only memory system showing gender differences in performance throughout the adult life span with a significantly higher performance for women.
Inhibition of thrombin receptor signaling by a G-protein coupled receptor kinase. Functional specificity among G-protein coupled receptor kinases. (1994)

The thrombin receptor, a member of the seven membrane-spanning superfamily of G-protein coupled receptors, is activated by an irreversible proteolytic mechanism, but signaling by activated thrombin receptors shuts off soon after receptor activation. This shut-off mechanism is thought to be required for concentration-dependent responses to thrombin and an important determinant of the cell's sensitivity to thrombin. We report that the thrombin receptor is rapidly phosphorylated upon activation, consistent with the action of a G-protein-coupled receptor kinase. Moreover, the G-protein coupled receptor kinase BARK2 (beta-adrenergic receptor kinase 2) blocked signaling by thrombin receptors coexpressed in Xenopus oocytes. In this system, rhodopsin kinase was inactive and BARK1 was markedly less effective than BARK2. Thrombin receptor mutants which lacked potential serine and threonine phosphorylation sites in the receptor's cytoplasmic tail were insensitive to inhibition by exogenous BARK2 but did confer concentration-dependent responses to thrombin. Our studies demonstrate that a G-protein coupled receptor kinase can shut off thrombin receptor signaling but that additional mechanism(s) for terminating signaling exist. These studies also reveal functional specificity among G-protein coupled receptor kinases in a novel in vivo reconstitution system and show that heterologous expression of these kinases can be used to manipulate cellular responsiveness.
Respiratory Syncytial Virus-Neutralizing Monoclonal Antibodies Motavizumab and Palivizumab Inhibit Fusion (2010)

Respiratory syncytial virus (RSV) is a major cause of virus-induced respiratory disease and hospitalization in infants. Palivizumab, an RSV-neutralizing monoclonal antibody, is used clinically to prevent serious RSV-related respiratory disease in high-risk infants. Motavizumab, an affinity-optimized version of palivizumab, was developed to improve protection against RSV. These antibodies bind RSV F protein, which plays a role in virus attachment and mediates fusion. Determining how these antibodies neutralize RSV is important to help guide development of new antibody drugs against RSV and, potentially, other viruses. This study aims to uncover the mechanism(s) by which palivizumab and motavizumab neutralize RSV. Assays were developed to test the effects of these antibodies at distinct steps during RSV replication. Pretreatment of virus with palivizumab or motavizumab did not inhibit virus attachment or the ability of F protein to interact with the target cell membrane. However, pretreatment of virus with either of these antibodies resulted in the absence of detectable viral transcription. These results show that palivizumab and motavizumab act at a point after F protein initiates interaction with the cell membrane and before virus transcription. Palivizumab and motavizumab also inhibited F protein-mediated cell-to-cell fusion. Therefore, these results strongly suggest that these antibodies block both cell-to-cell and virus-to-cell fusion, since these processes are likely similar. Finally, palivizumab and motavizumab did not reduce viral budding. Based on models developed from numerous studies of viral fusion proteins, our results indicate that these antibodies may prevent conformational changes in F protein required for the fusion process.
The BCR-ABL Story: Bench to Bedside and Back (2004)

The twenty-first century is beginning with a sharp turn in the field of cancer therapy. Molecular targeted therapies against specific oncogenic events are now possible. The BCR-ABL story represents a notable example of how research from the fields of cytogenetics, retroviral oncology, protein phosphorylation, and small molecule chemical inhibitors can lead to the development of a successful molecular targeted therapy. Imatinib mesylate (Gleevec, STI571, or CP57148B) is a direct inhibitor of ABL (ABL1), ARG (ABL2), KIT, and PDGFR tyrosine kinases. This drug has had a major impact on the treatment of chronic myelogenous leukemia (CML) as well as other blood neoplasias and solid tumors with etiologies based on activation of these tyrosine kinases. Analysis of CML patients resistant to BCR-ABL suppression by Imatinib mesylate coupled with the crystallographic structure of ABL complexed to this inhibitor have shown how structural mutations in ABL can circumvent an otherwise potent anticancer drug. The successes and limitations of Imatinib mesylate hold general lessons for the development of alternative molecular targeted therapies in oncology.
Iron, copper, zinc, and manganese transport and regulation in pathogenic Enterobacteria: correlations between strains, site of infection and the relative importance of the different metal transport systems for virulence (2013)

For all microorganisms, acquisition of metal ions is essential for survival in the environment or in their infected host. Metal ions are required in many biological processes as components of metalloproteins and serve as cofactors or structural elements for enzymes. However, it is critical for bacteria to ensure that metal uptake and availability is in accordance with physiological needs, as an imbalance in bacterial metal homeostasis is deleterious. Indeed, host defense strategies against infection either consist of metal starvation by sequestration or toxicity by the highly concentrated release of metals. To overcome these host strategies, bacteria employ a variety of metal uptake and export systems and finely regulate metal homeostasis by numerous transcriptional regulators, allowing them to adapt to changing environmental conditions. As a consequence, iron, zinc, manganese, and copper uptake systems significantly contribute to the virulence of many pathogenic bacteria. However, during the course of our experiments on the role of iron and manganese transporters in extraintestinal Escherichia coli (ExPEC) virulence, we observed that depending on the strain tested, the importance of tested systems in virulence may be different. This could be due to the different set of systems present in these strains, but literature also suggests that as each pathogen must adapt to the particular microenvironment of its site of infection, the role of each acquisition system in virulence can differ from a particular strain to another. In this review, we present the systems involved in metal transport by Enterobacteria and the main regulators responsible for their controlled expression. We also discuss the relative role of these systems depending on the pathogen and the tissues they infect.
Epstein-Barr Virus (EBV)-Encoded RNA Promotes Growth of EBV-Infected T Cells through Interleukin-9 Induction (2004)

EBV associates with various T-cell-proliferating diseases such as chronic active EBV infection and nasal lymphoma. In contrast to B cells, which are highly susceptible to EBV infection in vitro, T cells are refractory to EBV infection in vitro, and it has been difficult to examine the effects of EBV infection on T cells. We recently generated EBV recombinants with a selectable marker, which made it possible to select EBV-infected cells even when the efficiency of infection was low. Using the recombinant virus, we found that a human T-cell line, MT-2, was susceptible to EBV infection, and we succeeded in isolating EBV-infected cell clones with type II EBV latency, which was identical with those seen in EBV-infected T cells in vivo. EBV-infected MT-2 cell clones had shorter cell doubling times and higher saturation density than non-EBV-infected counterparts. We found that EBV-positive MT-2 cells expressed higher levels of interleukin (IL)-9 than EBV-negative MT-2 cells at the transcriptional level. It was also demonstrated that EBV-encoded small RNA was responsible for IL-9 expression. Addition of recombinant IL-9 accelerated the growth of MT-2 cells, whereas growth of the EBV-converted MT-2 cells was blocked by treatment with an anti-IL-9 antibody. These results suggest that IL-9 induced by EBV-encoded small RNA acts as an autocrine growth factor for EBV-infected T cells. Analysis of nasal lymphoma biopsies indicated that three of four specimens expressed IL-9. The present findings suggest that EBV directly affects the pathogenesis of EBV-associated T-cell diseases.
Antisense technology for the prevention or the treatment of cardiovascular disease: The next blockbuster? (2008)

Antisense technology might be a gateway to the treatment of diseases by targeting the expression of genes rather than permanently altering them. Thus, there will be fewer ethical concerns. Antisense oligonucleotides (ASO) can alter target gene expression by binding to RNA. Once bound, the ASO either disables or induces the degradation of the target RNA. This technology may be used to treat various conditions (including cancer, diabetes, and hypertension, as well as autoimmune and cardiovascular diseases). ASOs are potentially potent, selective and well-tolerated drugs. Mipomersen (ISIS 301012) inhibits human apolipoprotein (apo)B-100 synthesis and lowers circulating apoB and low-density lipoprotein cholesterol levels. ASO technology may provide a spectrum of agents targeting other vascular risk factors or mediators of atherosclerosis.
In contrast with docosahexaenoic acid, eicosapentaenoic acid and hypolipidaemic derivatives decrease hepatic synthesis and secretion of triacylglycerol by decreased diacylglycerol acyltransferase activity and stimulation of fatty acid oxidation (1999)

Hypolipidaemic fatty acid derivatives and polyunsaturated fatty acids decrease concentrations of plasma triacylglycerol by mechanisms that are not fully understood. Because poor susceptibility to beta- and/or omega-oxidation is apparently a determinant of the peroxisome proliferating and hypolipidaemic capacity of fatty acids and derivatives, the relative importance of activation of the peroxisome-proliferator-activated receptor alpha (PPARalpha), fatty acid oxidation and triacylglycerol synthesis were examined. We have compared the effects of differentially beta-oxidizable fatty acids on these parameters in primary cultures of rat hepatocytes. Tetradecylthioacetic acid (TTA), 2-methyleicosapentaenoic acid and 3-thia-octadecatetraenoic acid, which are non-beta-oxidizable fatty acid derivatives, were potent activators of a glucocorticoid receptor (GR)-PPARalpha chimaera. This activation was paradoxically reflected in an substantially increased oxidation of [1-(14)C]palmitic acid and/or oleic acid. The incorporation of [1-(14)C]palmitic acid and/or oleic acid into cell-associated and secreted triacylglycerol was decreased by 15-20% and 30% respectively with these non-beta-oxidizable fatty acid derivatives. The CoA ester of TTA inhibited the esterification of 1, 2-diacylglycerol in rat liver microsomes. Both eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) activated GR-PPARalpha. EPA increased the oxidation of [1-(14)C]palmitic acid but DHA had no effect. The CoA ester of EPA inhibited the esterification of 1, 2-diacylglycerol, whereas DHA-CoA had no effect. The ratio between synthesized triacylglycerol and diacylglycerol was lower in hepatocytes cultured with EPA in the medium compared with DHA or oleic acid, indicating a decreased conversion of diacylglycerol to triacylglycerol. Indeed, the incorporation of [1-(14)C]oleic acid into secreted triacylglycerol was decreased by 20% in the presence of EPA. In conclusion, a decreased availability of fatty acids for triacylglycerol synthesis by increased mitochondrial beta-oxidation and decreased triacylglycerol formation caused by inhibition of diacylglycerol acyltransferase might explain the hypolipidaemic effect of TTA and EPA.
Calcium Carbimide in Alcoholism Treatment. Part 1: a placebo‐controlled, double‐blind clinical trial of short‐term efficacy⋆ (1989)

A randomized, double-blind, placebo-controlled single cross-over study of the alcohol sensitizing drug, calcium carbimide (CC), was conducted in 128 patients with alcohol dependence. Seventy-one (55%) completed the 4-month study. Patients reported drinking and pill-taking behaviour, and submitted urines (for analysis of alcohol and the tablet marker riboflavin) on 97%, and 91% of treatment days, respectively. All of the 69 analyzable completers were abstinent on at least 85% of days, and 58% (40) were alcohol-free during the study. Medications were taken on at least 85% of days. Symptoms and adverse clinical findings were not increased in frequency during CC, compared to placebo. Seventy-eight per cent of the patients believed they had received CC throughout the study, suggesting that CC exerts a strong psychological deterrent effect. Alcohol consumption was significantly reduced to the same extent with CC and placebo, compared to pre-treatment levels.
Institutional Investors and Stock Market Volatility (2006)

We present a theory of excess stock market volatility, in which market movements are due to trades by very large institutional investors in relatively illiquid markets. Such trades generate significant spikes in returns and volume, even in the absence of important news about fundamentals. We derive the optimal trading behavior of these investors, which allows us to provide a unified explanation for apparently disconnected empirical regularities in returns, trading volume and investor size.
A Failure of Wound Healing Caused by an Imbalance of Bacteria (1997)

Wound healing can no longer be thought of as a generic term. Wounds heal by various processes such as coagulation, inflammation, matrix synthesis and deposition, angiogenesis, fibroplasia, epithelialization, contraction, and rem~deling.~~ The Wound Healing Society has stated that when wounds proceed through these processes in an orderly and timely manner and achieve sustained anatomic and functional integrity, they are considered acute wound^.'^ When they either do not proceed in an orderly and timely fashion or do so without achieving sustained anatomic and functional integrity, they are considered chronic. Tarnuzzer and SchultzM have suggested that repeated trauma, ischemia, and infection are leading causes of the pathobiology leading to wound chronicity.
Comparison of the Clinical Efficacy and Tolerance of Gentamicin PMMA Beads on Surgical Wire Versus Combined and Systemic Therapy for Osteomyelitis (1993)

These data do not prove a statistical superiority of conventional antibiotics or Septopal in the treatment of chronic osteomyelitis. This result, however, is complicated by the biased data set represented by the combined treatment. The data do suggest that cost of treatment is considerably less in patients who are treated with local antibiotics (i.e., Septopal) alone. The rate of adverse experiences was directly related to the use of parenteral antibiotics, with higher rates of adverse experiences in the conventional and combined treatment groups. Furthermore, the Cierny-Mader Physiologic Class had the best correlation with outcome, suggesting that host factors are probably of critical importance in inducing remission of chronic osteomyelitis. This protocol was not designed to test the role of debridement in the treatment of osteomyelitis: it was assumed that debridement would be the same in both groups. It is the investigators' strong opinion, however, that adequacy of debridement was an important determinant in quiescence or recurrence in the study patients. Similarly, there was no strict control for adequacy of soft-tissue coverage provided by local or distant tissue transfer. Again, the investigators believe that adequacy, including viability and durability, of soft-tissue covering was an important determinant for the end result in these patients. Other covariants such as smoking, history, nutritional status, and other measures of general health will be added to this model when data are available. This analysis will allow definition of the appropriate clinical situations in which use of Septopal alone or combined with parenteral antibiotic is indicated.
A Dramatic Substituent Effect in Silver(I)‐Catalyzed Regioselective Cyclization of ortho‐Alkynylaryl Aldehyde Oxime Derivatives (2008)

Abstract A dramatic substituent effect was found in the silver(I)‐catalyzed cyclization reaction of ortho ‐alkynylaryl aldehyde oxime derivatives. When R is an alkyl group, the Ag(I)‐catalyzed reaction in dimethylacetamide at 110 °C (conditions A) affords isoquinolines in good to excellent yields, in contrast, isoquinolin‐1(2 H )‐ones were produced in moderate to high yields under conditions B (dimethylformamide, room temperature) when R is an acetyl group. A plausible mechanism was proposed for this product selectivity control reaction (PSCR) by subtle structure modification.