gebhart/patrepeval huggingface dataset:
Detection of enterotoxigenic Escherichia coli after polymerase chain reaction amplification with a thermostable DNA polymerase (1989)

The direct identification of enterotoxigenic Escherichia coli from clinical specimens was examined by using the polymerase chain reaction (PCR) for amplifying the heat-labile toxin (LT) gene. Two synthetic primers, each of which was 20 bases in length, were used with the thermostable DNA polymerase from Thermus aquaticus to amplify the LT gene. The amplified PCR products were detected by either gel electrophoresis or hybridization to a 24-base synthetic oligonucleotide probe conjugated to alkaline phosphatase. The PCR method detected LT-positive bacteria but did not react with E. coli producing the heat-stable toxin, enteroinvasive E. coli, Salmonella typhi, Salmonella typhimurium, or Shigella dysenteriae. By the PCR method, a single bacterium could be detected following 30 cycles of amplification. The T. aquaticus DNA polymerase was inhibited by more than 10(3) organisms in the amplification reaction mixture. A group of 40 clinical specimens consisting of 16 LT bioassay-positive and 24 LT bioassay-negative stool specimens were tested by PCR for the presence of toxigenic E. coli. The total DNA from 100 microliters of stool specimen was extracted and partially purified with a commercially available ion-exchange column. All 16 of the bioassay-positive stool specimens were positive by PCR. In addition, one stool specimen which was bioassay negative for LT but positive for LT in a previous hybridization assay with a different LT probe was also positive by PCR. This may indicate that the LT gene is present but either is not expressed or is expressed below detectable levels. Amplification of specific DNA sequences by PCR provides a highly sensitive and specific tool for the detection of pathogenic microorganisms directly from clinical specimens without the need for prior isolation. This technique may find wide application in the detection of other organisms in addition to enterotoxigenic E.coli.
Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease (2001)

Osteoprotegerin (OPG), the neutralizing decoy receptor for the osteoclast activator RANK ligand, was measured in serum taken from patients with multiple myeloma at the time of diagnosis. Median OPG was lower in the patients with myeloma (7.4 ng/mL; range, 2.6-80; n = 225) than in healthy age- and sex-matched controls (9.0 ng/mL; range 5.1-130; n = 40; P =.02). Importantly, OPG levels were associated with degree of radiographically assessed skeletal destruction (P =.01). The median OPG level in patients lacking osteolytic lesions was 9.1 ng/mL, as compared with 7.6 ng/mL and 7.0 ng/mL, respectively, in patients with minor or advanced osteolytic disease. Furthermore, OPG levels were associated with World Health Organization performance status (P =.003) and correlated to serum levels of carboxy-terminal propeptide of type I procollagen (PICP; P <.001) but not with clinical stage or survival. These findings suggest impaired OPG function in myeloma and give a rationale for OPG as a therapeutic agent against myeloma bone disease.
Pathophysiology of Migraine (2006)

The cause and pathophysiology of migraine are not well understood. Over the years research into migraine pathophysiology has focused on the physiology and pharmacology of the headache, the changes in cerebral cortex associated with the symptoms of the aura, and more recently the genetics underlying the migraine syndromes. In this discussion, the neuroanatomical structures activated during migraine attacks, the traditional theories of migraine that serve as the foundation for current research, and the essential findings from current migraine pathophysiological research will be reviewed. Investigations in migraine can be divided into those related to the brain events initiating a migraine attack, those examining the mechanisms of activation and transmission within trigeminal afferent neurons, and those focused on the effect of and the modulation of nociception trigeminal input within the central nervous system.
Ventricular Assist Device Implantation Corrects Myocardial Lipotoxicity, Reverses Insulin Resistance, and Normalizes Cardiac Metabolism in Patients With Advanced Heart Failure (2012)

Mechanical unloading after left ventricular assist device implantation corrects systemic and local metabolic derangements in advanced heart failure, leading to reduced myocardial levels of toxic lipid intermediates and improved cardiac insulin signaling.
A phase I trial of tumor lysate-pulsed dendritic cells in the treatment of advanced cancer. (2002)

The administration of tumor lysate-pulsed DCs is nontoxic and capable of inducing immunological response to tumor antigen. Additional studies are necessary to improve tumor rejection responses.
Aromatic-dependent Salmonella dublin as a parenteral modified live vaccine for calves (1984)

A virulent Salmonella dublin isolate was made histidine-requiring (his-) to allow recognition. The his- derivative, SL1367 (still calf-virulent), was then given by transduction and mutation, a transposon-generated non-reverting aromatic biosynthesis (aro) defect; this defect caused loss of virulence for the mouse. The his- aro- derivative strain, SL1438, was effective as a live vaccine in mice. Twenty male Holstein calves were divided into 4 groups. Groups I, II, and III were vaccinated IM at 2 weeks and at 3 weeks of age with aromatic-dependent (aro-) S dublin strain SL1438. Groups I and III received freshly prepared vaccine and group II received lyophilized vaccine. Serious adverse reactions to the vaccination were not seen. After vaccination, the mean maximum increase in rectal temperature was 1.8 C in group I and III calves and 0.6 C in group II calves. Fewer group II calves developed diarrhea (1 of 5) or positive blood cultures (0 of 5) after vaccination compared with group I and III calves (6 of 10 and 5 of 10, respectively). Postvaccination diarrhea was mild and of short duration. Group IV was comprised of 5 nonvaccinated calves. At 5 weeks of age, all calves were challenge exposed orally. Group I, II, and IV calves were challenge exposed with 10(11) virulent S dublin SL1367. Group III was challenge exposed with 10(11) virulent S typhimurium UCD 108-11. Subsequently, fever and diarrhea (lasting 1 to 3 days), but no deaths, were observed in the vaccinated calves. Four of the 5 nonvaccinated (group IV) calves died (P less than 0.001) within 8 days after challenge exposure. Aro- S dublin SL 1438 did not cause serious adverse effects and provided protection against oral challenge exposure with either virulent S dublin or S typhimurium.
p21-activated Kinase-aberrant Activation and Translocation in Alzheimer Disease Pathogenesis (2008)

Defects in dendritic spines and synapses contribute to cognitive deficits in mental retardation syndromes and, potentially, Alzheimer disease. p21-activated kinases (PAKs) regulate actin filaments and morphogenesis of dendritic spines regulated by the Rho family GTPases Rac and Cdc42. We previously reported that active PAK was markedly reduced in Alzheimer disease cytosol, accompanied by downstream loss of the spine actin-regulatory protein Drebrin. beta-Amyloid (Abeta) oligomer was implicated in PAK defects. Here we demonstrate that PAK is aberrantly activated and translocated from cytosol to membrane in Alzheimer disease brain and in 22-month-old Tg2576 transgenic mice with Alzheimer disease. This active PAK coimmunoprecipitated with the small GTPase Rac and both translocated to granules. Abeta42 oligomer treatment of cultured hippocampal neurons induced similar effects, accompanied by reduction of dendrites that were protected by kinase-active but not kinase-dead PAK. Abeta42 oligomer treatment also significantly reduced N-methyl-d-aspartic acid receptor subunit NR2B phosphotyrosine labeling. The Src family tyrosine kinase inhibitor PP2 significantly blocked the PAK/Rac translocation but not the loss of p-NR2B in Abeta42 oligomer-treated neurons. Src family kinases are known to phosphorylate the Rac activator Tiam1, which has recently been shown to be Abeta-responsive. In addition, anti-oligomer curcumin comparatively suppressed PAK translocation in aged Tg2576 transgenic mice with Alzheimer amyloid pathology and in Abeta42 oligomer-treated cultured hippocampal neurons. Our results implicate aberrant PAK in Abeta oligomer-induced signaling and synaptic deficits in Alzheimer disease.
COST-EFFECTIVE SNOW AND ICE CONTROL FOR THE 1990S (1993)

Road weather information systems (RWISs) are now widely used operationally by road masters to determine when to use deicing chemicals on roads. Data from such systems can also be used to assess the cost-effectiveness of RWISs. To account for the variation in winter weather from year-to-year (temporal) and across an area (spatial), three winter severity indexes are examined that can be compared with winter maintenance expenditures.
Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans (2002)

Glucagon-like peptide-1 (GLP-1) relaxes the stomach during fasting but decreases hunger and food consumption and retards gastric emptying. The interrelationships between volume, emptying, and postprandial symptoms in response to GLP-1 are unclear. We performed, in healthy human volunteers, a placebo-controlled study of the effects of intravenous GLP-1 on gastric volume using 99m Tc-single photon emission computed tomography imaging, gastric emptying of a nutrient liquid meal (Ensure) using scintigraphy, maximum tolerated volume (MTV) of Ensure, and postprandial symptoms 30 min after MTV. The role of vagal cholinergic function in the effects of GLP-1 was assessed by human pancreatic polypeptide (HPP) response to the Ensure meal. GLP-1 increased fasting and postprandial gastric volumes and retarded gastric emptying; MTV and postprandial symptoms were not different compared with controls. Effects on postprandial gastric function were associated with reduced postprandial HPP levels. GLP-1 does not induce postprandial symptoms despite significant inhibition of gastric emptying and vagal function; this may be partly explained by the increase in postprandial gastric volume.
Privacy, sex, and norms : An indirect control definition (2000)

Au vu des emplois contradictoires du terme de vie privee, l'auteur propose une analyse visant a redefinir ce qu'est la vie privee. S'appuyant sur l'etude du comportement des primates et sur la psychologie evolutionniste, l'auteur associe la vie privee a une attitude humaine de defense primordiale, ainsi qu'a une tendance tout autant primordiale a surveiller et a sanctionner le comportement des autres. L'analyse revele la tension entre ces deux poles, que les normes specifiques a chaque culture viennent modeler. La definition proposee considere le droit a la vie privee comme le droit qu'un individu detient quand les autres respectent ses preferences culturellement normales en matiere de surveillance et d'information le concernant.
Dynamics of the Hippocampal Ensemble Code for Space (1993)

Ensemble recordings of 73 to 148 rat hippocampal neurons were used to predict accurately the animals' movement through their environment, which confirms that the hippocampus transmits an ensemble code for location. In a novel space, the ensemble code was initially less robust but improved rapidly with exploration. During this period, the activity of many inhibitory cells was suppressed, which suggests that new spatial information creates conditions in the hippocampal circuitry that are conducive to the synaptic modification presumed to be involved in learning. Development of a new population code for a novel environment did not substantially alter the code for a familiar one, which suggests that the interference between the two spatial representations was very small. The parallel recording methods outlined here make possible the study of the dynamics of neuronal interactions during unique behavioral events.
Role of transport systems in amino acid metabolism: leucine toxicity and the branched-chain amino acid transport systems (1977)

The livR locus, which leads to a trans-recessive derepression of branched-chain amino acid transport and periplasmic branched-chain amino acid-binding proteins, is responsible for greatly increased sensitivity toward growth inhibition by leucine, valine, and serine and, as shown previously, for increased sensitivity toward toxicity by branched-chain amino acid analogues, such as 4-azaleucine or 5',5',5'-trifluoroleucine. These phenotypes are similar to those of relA mutants; however, the livR mutants retain the stringent response of ribonucleic acid synthesis. However, an increase in the rate of transport or in the steady-state intracellular level of amino acids in the livR strain cannot completely account for this sensitivity. The ability of the LIV-I transport system to carry out exchange of pool amino acids for extracellular leucine is a major factor in leucine sensitivity. The previous finding that inhibition of threonine deaminase by leucine contributes to growth inhibition is confirmed by simulating the in vivo conditions using a toluene-treated cell preparation with added amino acids at levels corresponding to the internal pool. The relationship between transport systems and corresponding biosynthetic pathways is discussed and the general principle of a coordination in the regulation of transport and biosynthetic pathways is forwarded. The finding that the LIV-I transport system functions well for amino acid exchange in contrast to the LIV-II system provides another feature that distinguishes these systems in addition to previously described differences in regulation and energetics.
Modified flame ionization detector for the analysis of large molecular weight polar compounds by capillary supercritical fluid chromatography (1985)

Abstract The modifications made to a flame ionization detector (FID) to facilitate the detection of large molecular weight polar compounds analyzed by capillary supercritical fluid chromatography are described. Some specific examples are given to demonstrate that polar compounds can be effectively eluted using deactivated fused silica capillary columns and supercritical carbon dioxide at 40°C.
On Studies of Mutual Fund Performance, 1962–1991 (1993)

(1993). On Studies of Mutual Fund Performance, 1962–1991. Financial Analysts Journal: Vol. 49, No. 1, pp. 42-50.
Visualization of navigation patterns on a Web site using model-based clustering (2000)

We present a new methodology for visualizing navigation patterns on a Web site. In our approach, we rst partition site users into clusters such that only users with similar navigation paths through the site are placed into the same cluster. Then, for each cluster, we display these paths for users within that cluster. The clustering approach we employ is model based (as opposed to distance based) and partitions users according to the order in which they request Web pages. In particular, we cluster users by learning a mixture of rst-order Markov models using the ExpectationMaximization algorithm. Our algorithm scales linearly with both number of users and number of clusters, and our implementation easily handles millions of users and thousands of clusters in memory. In the paper, we describe the details of our technology and a tool based on it called WebCANVAS. We illustrate the use of our technology on user-traAEc data from msnbc.com.
Pregnancy-Associated Depression of Cell-Mediated Immunity (1984)

Pregnancy has been known for some time to be associated with depressed aspects of cell-mediated immunity (CMI) that permit fetal retention but that also may interfere with resistance to specific infectious and neoplastic agents. Clinical and laboratory findings of loss of resistance have been extensively documented. Gestation appears to be associated with depression of selective aspects of CMI. Levels of hormones and other serum factors that may modulate lymphocyte or macrophage synthesis, activation, and/or function shift considerably during pregnancy. The induction and maintenance of pregnancy-associated immune deficiency probably rely on a multifactorial mechanism. Further research is needed to identify agents that would prevent fetal rejection while permitting adequate defense against infection and malignancy; to identify strains particularly dangerous during gestation; and to develop vaccines against the nonshared antigens of such strains.
Identification of a novel senolytic agent, navitoclax, targeting the Bcl‐2 family of anti‐apoptotic factors (2015)

Clearing senescent cells extends healthspan in mice. Using a hypothesis-driven bioinformatics-based approach, we recently identified pro-survival pathways in human senescent cells that contribute to their resistance to apoptosis. This led to identification of dasatinib (D) and quercetin (Q) as senolytics, agents that target some of these pathways and induce apoptosis preferentially in senescent cells. Among other pro-survival regulators identified was Bcl-xl. Here, we tested whether the Bcl-2 family inhibitors, navitoclax (N) and TW-37 (T), are senolytic. Like D and Q, N is senolytic in some, but not all types of senescent cells: N reduced viability of senescent human umbilical vein epithelial cells (HUVECs), IMR90 human lung fibroblasts, and murine embryonic fibroblasts (MEFs), but not human primary preadipocytes, consistent with our previous finding that Bcl-xl siRNA is senolytic in HUVECs, but not preadipocytes. In contrast, T had little senolytic activity. N targets Bcl-2, Bcl-xl, and Bcl-w, while T targets Bcl-2, Bcl-xl, and Mcl-1. The combination of Bcl-2, Bcl-xl, and Bcl-w siRNAs was senolytic in HUVECs and IMR90 cells, while combination of Bcl-2, Bcl-xl, and Mcl-1 siRNAs was not. Susceptibility to N correlated with patterns of Bcl-2 family member proteins in different types of human senescent cells, as has been found in predicting response of cancers to N. Thus, N is senolytic and acts in a potentially predictable cell type-restricted manner. The hypothesis-driven, bioinformatics-based approach we used to discover that dasatinib (D) and quercetin (Q) are senolytic can be extended to increase the repertoire of senolytic drugs, including additional cell type-specific senolytic agents.
High-Detectivity Polymer Photodetectors with Spectral Response from 300 nm to 1450 nm (2009)

Sensing from the ultraviolet-visible to the infrared is critical for a variety of industrial and scientific applications. Today, gallium nitride-, silicon-, and indium gallium arsenide--based detectors are used for different sub-bands within the ultraviolet to near-infrared wavelength range. We demonstrate polymer photodetectors with broad spectral response (300 to 1450 nanometers) fabricated by using a small-band-gap semiconducting polymer blended with a fullerene derivative. Operating at room temperature, the polymer photodetectors exhibit detectivities greater than 10(12) cm Hz(1/2)/W and a linear dynamic range over 100 decibels. The self-assembled nanomorphology and device architecture result in high photodetectivity over this wide spectral range and reduce the dark current (and noise) to values well below dark currents obtained in narrow-band photodetectors made with inorganic semiconductors.
Nucleotide sequence of the EcoR1 D fragment of adenovirus 2 genome (1980)

The entire nucleotide sequence of the Ad. 2 EcoRI D fragment has been determined using the Maxam and Gilbert method. This sequence of 2678 bp contains informations relative to late mRNAs ending at position 78 and for which an AATAAA sequence corresponding to their 3' ends is found at residue number 833. Position of the PVIII mRNA is determined thus allowing deduction of the probable amino acid sequence of the PVIII protein. The position and the sequence of the first leader of early 3 mRNAs is determined as well as the sequence and position of the second early leader of region 3 mRNAs, which also correspond to the "y" leader of the fiber mRNA. Following the localization of an open reading frame in which an ATG could initiate protein synthesis it can be predicted that 3a, b, c mRNAs code for the 16K early protein and the probable amino acid sequence of this protein can be deduced. The CAGTTT sequence frequently present at the 5' end of a leader or of a mRNA body as well as the GGTGAG sequence which is found at the 3' end of several leaders were used to postulate the position of various early mRNAs of region 3 and to suggest the existence of an additional splicing event during the processing of mRNAs 3a, b and c. They were also used to predict the position of the additional "x" late leaders. The imbrication of information concerning (i) the family of late mRNAs ending at position 78, (ii) the position of the "x" leader and the "y" leader and (iii) the beginning of early region 3 is also depicted.
Characterization of single-chain antibody (sFv)-toxin fusion proteins produced in vitro in rabbit reticulocyte lysate. (1993)

Chimeric proteins consisting of a fusion between binding-deficient mutants of diphtheria toxin (DT) or Pseudomonas exotoxin A (PE) and a single-chain antibody (E6 sFv) against the human transferrin receptor (TfnR) were expressed in a rabbit reticulocyte lysate system. Molecules utilizing PE40 (the carboxyl terminus 40 kDa of PE, lacking the binding domain) exhibited significant E6 sFv-mediated, cell type-specific cytotoxicity (IC50 1 x 10(-10) M) against a human erythroleukemia-derived cell line, K562. In contrast, a fusion protein between the same sFv and a DT mutant, DTM1 (containing two amino acid substitutions in the binding domain [S(508)F, S(525)F]) was not significantly cytotoxic, despite being enzymatically active. A tripartite protein in the form NH2-DTM1-E6 sFv-PE40-COOH exhibited cytotoxicity comparable to that of the PE40-sFv fusion (IC50 1 x 10(-10) M), suggesting that the deficit in activity of DTM1-sFv is not a function of misfolding of the sFv moiety or of a reduced ability to bind TfnR. In contrast to DTM1-E6 sFv, a fusion protein between a second DT mutant, CRM 107 [S(525)F], and the E6 sFv was specifically cytotoxic (IC50 1 x 10(-9) M), and toxicity could be blocked by addition of excess E6 antibody. The cell-free in vitro expression system we describe is rapid and may be used to express functional toxin-sFv fusion proteins. No protein refolding procedures are required, and the technique may be used to express proteins which, due to restrictions imposed on manipulation of toxin-encoding genes in Escherichia coli, could not be produced by more conventional methods.
Complement activation mediates cetuximab inhibition of non-small cell lung cancer tumor growth in vivo (2010)

We demonstrate for the first time that the in vivo antitumor activity of cetuximab can be associated with a complement-mediated immune response. These results may have important implications for the development of new cetuximab-based therapeutic strategies and for the identification of markers that predict clinical response.