gebhart/patrepeval huggingface dataset:
5-HT1B Receptor Knock-Out Mice Exhibit Increased Exploratory Activity and Enhanced Spatial Memory Performance in the Morris Water Maze (1999)

In an attempt to characterize the contribution of the 5-HT1B receptor to behavior, 5-HT1B knock-out (KO) mice were subjected to a battery of behavioral paradigms aimed at differentiating various components of cognitive and emotional behaviors. In an object exploration task, wild-type (WT) and 5-HT1B KO mice did not differ in locomotor activity. 5-HT1B KO mice, however, displayed lower thigmotaxis (an index of anxiety) associated with a higher level of object exploratory activity, but no genotype differences were observed in the elevated plus maze. 5-HT1B KO mice also displayed a lack of exploratory habituation. In the spatial version of the Morris water maze, 5-HT1B KO mice showed higher performances in acquisition and transfer test, which was not observed in the visual version of the task. No genotype differences were found in contextual fear conditioning, because both WT and 5-HT1B KO mice were able to remember the context where they had received the aversive stimulus. The deletion of the 5-HT1B receptor, associated with appropriate behavioral paradigms, thus allowed us to dissociate anxiety from response to novelty, and perseverative behavior (lack of habituation) from adaptive behavioral inhibition underlying cognitive flexibility (transfer stage in the water maze). The deletion of the 5-HT1B receptor did not result in significant developmental plasticities for other major 5-HT receptor types but may have influenced other neurotransmission systems. The 5-HT1B receptor may be a key target for serotonin in the modulation of cognitive behavior, particularly in situations involving a high cognitive demand.
Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts (1993)

Granulation tissue fibroblasts (myofibroblasts) develop several ultrastructural and biochemical features of smooth muscle (SM) cells, including the presence of microfilament bundles and the expression of alpha-SM actin, the actin isoform typical of vascular SM cells. Myofibroblasts have been proposed to play a role in wound contraction and in retractile phenomena observed during fibrotic diseases. We show here that the subcutaneous administration of transforming growth factor-beta 1 (TGF beta 1) to rats results in the formation of a granulation tissue in which alpha-SM actin expressing myofibroblasts are particularly abundant. Other cytokines and growth factors, such as platelet-derived growth factor and tumor necrosis factor-alpha, despite their profibrotic activity, do not induce alpha-SM actin in myofibroblasts. In situ hybridization with an alpha-SM actin probe shows a high level of alpha-SM actin mRNA expression in myofibroblasts of TGF beta 1-induced granulation tissue. Moreover, TGF beta 1 induces alpha-SM actin protein and mRNA expression in growing and quiescent cultured fibroblasts and preincubation of culture medium containing whole blood serum with neutralizing antibodies to TGF beta 1 results in a decrease of alpha-SM actin expression by fibroblasts in replicative and non-replicative conditions. These results suggest that TGF beta 1 plays an important role in myofibroblast differentiation during wound healing and fibrocontractive diseases by regulating the expression of alpha-SM actin in these cells.
Seroepidemiology of Human Bocaviruses 1–4 (2011)

HBoV2-4 infect humans less commonly and elicit weaker B-cell responses than HBoV1. In our study HBoV2-4 did not seem to have a major etiological role in wheezing. Cross-reactivity with HBoV2-4 IgG partially accounts for the high HBoV1 seroprevalences previously reported. Correction for cross-reactivity is a prerequisite for VLP-based HBoV seroepidemiology.
Polysorbate 20 prevents the precipitation of a monoclonal antibody during shear (2009)

Monoclonal antibodies (MAbs) are widely used as therapeutic proteins and they are frequently exposed to a high degree of stress during manufacturing or delivery. MAbs shear thin upon increasing shear rates. After undergoing multiple shear cycles, with a cone-and-plate rheometer, the solution viscosity of high concentration antibodies increases due to the formation of insoluble aggregates. These shear-induced insoluble aggregates do not form when polysorbate 20 is present in solution. We hypothesize that monoclonal antibodies form a thin protein layer at the air-water interface. MAbs at the interface expose their hydrophobic core to air leading to unfolding, multiple non-specific intermolecular interactions and, upon continuous high shear, precipitation. Surface tension analysis confirms that monoclonal antibodies are surface active and that polysorbate 20 can prevent their interaction with the air-water interface. In addition, we complement these findings with a viscometer that measures bulk viscosity without the influence of an air-liquid interfacial viscosity and find that the bulk viscosity increases slightly when Mab solutions contained polysorbate 20. These methods of analysis could be used when designing manufacturing systems in which a protein solution is subject to shear forces.
A Novel WD Repeat Protein Component of the Methylosome Binds Sm Proteins (2002)

We have recently described a large (20 S) protein arginine methyltransferase complex, termed the methylosome, that contains the methyltransferase JBP1 (PRMT5) and the pICln protein. The methylosome functions to modify specific arginines to dimethylarginines in the arginine- and glycine-rich domains of several spliceosomal Sm proteins, and this modification targets these proteins to the survival of motor neurons (SMN) complex for assembly into small nuclear ribonucleoprotein (snRNP) core particles. Here, we describe a novel component of the methylosome, a 50-kilodalton WD repeat protein termed methylosome protein 50 (MEP50). We show that MEP50 is important for methylosome activity and binds to JBP1 and to a subset of Sm proteins. Because WD repeat proteins provide a platform for multiple protein interactions, MEP50 may function to mediate the interaction of multiple substrates with the methylosome. Interestingly, all of the known components of the methylosome bind Sm proteins, suggesting that in addition to producing properly methylated substrates for the SMN complex, the methylosome may be involved in Sm protein rearrangements or pre-assembly required for snRNP biogenesis.
Stereoselective Synthesis of meso-2,6-Diaminopimelic Acid and Its Selectively Protected Derivatives (1998)

Four synthetic routes to selectively protected derivatives and isomers of meso-diaminopimelic acid (DAP) (1a), a key constituent of bacterial peptidoglycan, were investigated. N-(tert-butyloxycarbonyl)-d-allylglycine (2) and N-(benzyloxycarbonyl)-l-allylglycine (4) were esterified to ethylene glycol and cyclized via olefin metathesis to a protected derivative 7 of 2,7-diaminosuberic acid. Analogous linking of propane-1,3-diol with 2 and potential precursors of N-(benzyloxycarbonyl)-l-vinylglycine moieties, such as N-(benzyloxycarbonyl)-l-glutamate or N-(benzyloxycarbonyl)-l-methionine sulfoxide, gave 12 or 15, both of which produced the α,β-unsaturated ester 14 upon attempted generation of the vinylglycine precursor for olefin metathesis to DAP derivatives. An alternative route, based on SnCl4-catalyzed ene reaction of methyl N-(benzyloxycarbonyl)-l-allylglycinate (18) with glyoxylate esters of phenylcyclohexanol isomers as chiral auxiliaries, gave ca. 85:15 ratios of diastereomeric alcohols (19 or 20). These could be transformed to DAP derivatives in a series of steps employing azide displacement of corresponding mesylates to introduce the second nitrogen. A third method, involving reduction of pure dimethyl (6S)-2-keto-6-[N-(benzyloxycarbonyl)amino]pimelate (32) to the corresponding alcohol 33 with (S)-binaphthol−ruthenium catalyst as the key step, gives a 79:21 isomeric ratio. The fourth route employs the bis(oxazoline)−copper complex 41 as a chiral catalyst for the ene reaction of methyl (S)-4-(phenylthio)allylglycinate (39) and methyl glyoxylate to afford 42 in 94:6 isomeric ratio. Nickel boride removal of sulfur and the double bond in the presence of the Cbz group gives the desired alcohol, dimethyl (2S,6S)-6-[N-(benzyloxycarbonyl)amino]-2-hydroxyheptane-1,7-dioate (33). The required selectively protected second nitrogen is introduced using Mitsunobu inversion with N-tert-butyl [[2-(trimethylsilyl)ethyl]sulfonyl]carbamate (34) as a key step.
Kallistatin is a potent new vasodilator. (1997)

Kallistatin is a serine proteinase inhibitor which binds to tissue kallikrein and inhibits its activity. The aim of this study is to evaluate if kallistatin has a direct effect on the vasculature and on blood pressure homeostasis. We found that an intravenous bolus injection of human kallistatin caused a rapid, potent, and transient reduction of mean arterial blood pressure in anesthetized rats. Infusion of purified kallistatin (0.07-1.42 nmol/kg) into cannulated rat jugular vein produced a 20-85 mmHg reduction of blood pressure in a dose-dependent manner. Hoe 140, a bradykinin B2-receptor antagonist, had no effect on the hypotensive effect of kallistatin yet it abolished the blood pressure-lowering effect of kinin and kallikrein. Relaxation of isolated aortic rings by kallistatin was observed in the presence (ED50 of 3.4 x 10(-9) M) and in the absence of endothelium (ED50 of 10(-9) M). Rat kallikrein-binding protein, but not kinin or kallikrein, induced vascular relaxation of aortic rings. Neither Hoe 140 nor Nomega-nitro--arginine methyl ester, a nitric oxide synthase inhibitor, affected vasorelaxation induced by kallistatin. Kallistatin also caused dose-dependent vasodilation of the renal vasculature in the isolated, perfused rat kidney. Specific kallistatin-binding sites were identified in rat aorta by Scatchard plot analysis with a Kd of 0.25+/-0.07 nM and maximal binding capacity of 47.9+/-10.4 fmol/mg protein (mean+/-SEM, n = 3). These results indicate that kallistatin is a potent vasodilator which may function directly through a vascular smooth muscle mechanism independent of an endothelial bradykinin receptor. This study introduces the potential significance of kallistatin in directly regulating blood pressure to reduce hypertension.
Human Papillomavirus DNA in Genital Tract Lesions Histologically Negative for Condylomata (1990)

Koilocytotic atypia (nuclear atypia in conjunction with perinuclear halos) is diagnostic of condylomata of the lower female genital tract, over 90% of which contain human papillomavirus (HPV) DNA. Genital tract lesions may be clinically suggestive of condylomata but lack clear-cut koilocytotic atypia. Of 57 vulvar and 60 cervical lesions that lacked clear-cut koilocytotic atypia, four (7%) and two (3%), respectively, had HPV DNA detected by in situ analysis. Using Southern blot analysis, HPV DNA was detected in five of 27 (19%) and 20 of 55 (36%) vulvar and cervical lesions, respectively, that lacked koilocytotic atypia. When analyzed with the polymerase chain reaction (PCR), HPV DNA was detected in six of 22 (27%) and three of 18 (17%) vulvar and cervical lesions, respectively, that lacked koilocytotic atypia. These findings demonstrate that infection by HPV may be found in genital tract lesions that lack koilocytotic atypia. The lower detection rate of HPV in cervical lesions that lacked koilocytotic atypia with PCR as compared with Southern blot analysis may be related to the relatively high proportion of "novel" types (related to, but distinct from, the HPV types in the probe) in such lesions. The increase in the detection rate in vulvar lesions that lacked koilocytotic atypia with PCR compared with in situ hybridization suggests that about one third of such lesions are HPV related, but that in such cases the copy number of the virus is typically below the threshold of the in situ analysis.
Virologic and Immunologic Consequences of Discontinuing Combination Antiretroviral-Drug Therapy in HIV-Infected Patients with Detectable Viremia (2001)

Despite the presence of reduced drug susceptibility, antiretroviral-drug therapy can provide immunologic and virologic benefit. This benefit reflects continued antiviral-drug activity and the maintenance of a viral population with a reduced replicative capacity.
Calcium-dependent inactivation of synaptic NMDA receptors in hippocampal neurons (1995)

1. We examined whether synaptically activated N-methyl-D-aspartate (NMDA) receptors are regulated by intracellular calcium in cultured hippocampal neurons by comparing excitatory postsynaptic currents (EPSCs) to the previously described calcium-dependent regulation of whole cell NMDA currents. Standard whole cell recording and fast application methods were used. 2. Low-frequency (0.2 Hz) stimulation of EPSCs in the presence of 2-amino-5-phosphonovalerate (AP5) evoked a constant amplitude alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated EPSC. On removal of AP5 in Ca(2+)-containing solutions, the amplitude of the slow NMDA receptor-mediated EPSC decreased by approximately 50% during the next 10 stimuli. The decrease in the EPSC was dependent on the extracellular calcium concentration and stimulus frequency, consistent with Ca(2+)-dependent desensitization/inactivation of postsynaptic NMDA receptors. A whole cell prepulse of NMDA (10 microM, 10 s) in Ca(2+)-containing solutions inhibited the slow EPSC to a similar degree. A series of slow EPSCs also produced Ca(2+)-dependent inactivation of whole cell NMDA currents evoked in low calcium solutions. 3. These results demonstrate that synaptic NMDA receptors are inactivated by intracellular calcium and that calcium entry through synaptically activated NMDA receptors is sufficient to provide feedback inhibition of the slow EPSC.
Poly(lactic acid)/organoclay nanocomposites: Thermal, rheological properties and foam processing (2005)

Abstract In this study, polymer nanocomposites based on poly(lactic acid) (PLA) and organically modified layered silicates (organoclay) were prepared by melt mixing in an internal mixer. The exfoliation of organoclay could be attributed to the interaction between the organoclay and PLA molecules and shearing force during mixing. The exfoliated organoclay layers acted as nucleating agents at low content and as the organoclay content increased they became physical hindrance to the chain mobility of PLA. The thermal dynamic mechanical moduli of nanocomposites were also improved by the exfoliation of organoclay; however, the improvement was reduced at high organoclay content. The dynamic rheological studies show that the nanocomposites have higher viscosity and more pronounced elastic properties than pure PLA. Both storage and loss moduli increased with silicate loading at all frequencies and showed nonterminal behavior at low frequencies. The nanocomposites and PLA were then foamed by using the mixture of CO 2 and N 2 as blowing agent in a batch foaming process. Compared with PLA foam, the nanocomposite foams exhibited reduced cell size and increased cell density at very low organoclay content. With the increase of organoclay content, the cell size was decreased and both cell density and foam density were increased. © 2005 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 43: 689–698, 2005
Improvement in buried silicon nitride silicon-on-insulator structures by fluorine-ion implantation (1998)

As an effort to improve buried Si3N4–Si interfaces in silicon-on-insulator (SOI) structures, fluorine was implanted either before or after the synthesis of buried silicon nitride layers by high dose nitrogen ion implantation. In these synthesized SOI structures, the thickness of Si overlayer and the buried silicon nitride layer was found to be 2400±25 and 1725±25 Å, respectively. Auger electron spectroscopy depth profile analysis illustrates that the fluorine ion implantation in the SOI structures modifies the distribution of nitrogen that results in better stoichiometry of the buried silicon nitride layers and abrupt Si3N4–Si interfaces. Current–voltage and high frequency capacitance–voltage characteristics were measured, and electrical breakdown measurements were performed on metal-nitride-silicon (MNS) structures, fabricated after removing the Si overlayer in the SOI structures. In the fluorine-implanted SOI specimens, the buried Si3N4 layers show a higher breakdown field strength of 4.4–5.2 MV/cm as compared to 3.5–4.0 MV/cm in the nonfluorine-implanted one. The capacitance–voltage analysis of the MNS capacitors reveals that the buried Si3N4–Si substrate interface exhibits a better quality with reduced fixed insulator charge and interface state densities after the fluorine ion implantation. Midgap interface state density at the buried Si3N4–Si substrate interface was as low as 1.48×1011 cm−2 eV−1 after the fluorine implantation, which is comparable to that of silicon nitride films deposited on silicon by the conventional low pressure chemical vapor deposition technique. The role of fluorine in improving the basic electrical properties of these SOI structures has been discussed.
Caracterización y origen de las dolomías del sector sudeste de Picos de Europa (Norte de España) (1993)

En el presente trabajo se pone de manifiesto la existencia de un proceso de dolomitización que afectó al sector sudeste de la región de Picos de Europa. Las dolomías formadas como consecuencia de este proceso son rocas de geometría muy variada e irregular, que recuerda a la de las masas intrusivas. Su composición química muestra un ligero exceso en calcio respecto a la fórmula estequiométrica de la dolomita. Sus contenidos en hierro y estroncio son bajos respecto a los de otras dolomías comparables. El volumen de dolomías formado es mucho mayor en la Unidad Frontal de Picos de Europa que en Unidades estructurales superiores. Los procesos dolomitizadores obedecen a un modelo de dolomitización epigenético y son previos a la deposición de mineralizaciones de Pb-Zn. Se propone un modelo de dolomitización per ascensum a partir de aguas de formación de los sedimentos de la región de Pisuerga-Carrión. En cuanto a la edad, la dolomitización es posterior al Estefaniense B inferior y posiblemente anterior a un momento del Pérmico no determinado.
[Pharmacodynamics and pharmacokinetics of dihydroetorphine hydrochloride administered sublingually in mice and rats]. (1988)

The analgesia. respiratory depression and immobilization in mice and rats after dihydroetorphine hydrochloride (DHE) administered sublingually (sl) were similar to those after DHE administered subcutaneously (sc), but the effective doses of sl DHE were larger than those of sc DHE. After sl [15. 16-3H] DHE 2.36 vg/kg (1/2 analgesia ED50) for mice. K^=0.273 min-l, tl(a) = 2.54 min, tmax = 10.9 min. Cmax = 202 pg/ml, K = 0.0166 min-l. t= =41.7 min, AUCO-189min = 18.2 ng.min/ml. The elimination of [15,16-3H]DHE from the blood was conformed to the single compartment model. The relative apparent bioavailability of sl [15, 16-3H]DHE for mice was l.9.2% of sc [15, 16-3H]DHE. The effects of sl DHE were easily antagonized by nalorphine. It had been recommended to test the sublingual tablet of DHE in the terminal cancer patients with pain.
Combined single-molecule force and fluorescence measurements for biology. (2003)

Recent advances in single-molecule techniques allow the application of force to an individual biomolecule whilst simultaneously monitoring its response using fluorescent probes. The effects of applied mechanical load on single-enzyme turnovers, biomolecular interactions and conformational changes can now be studied with nanometer precision and millisecond time resolution.
Nanofiber scaffolding for improved neural electrode biocompatibility (2003)

The prospect of obtaining neural signals directly from the brain for prosthetic control and chronic research has been limited by the brains natural immune response to current thin film neural electrodes. In this study we have attempted to coat ceramic thin film neural electrodes with a nanostructured, biodegradable polymer matrix for subsequent use in localized, controlled drug delivery and glial sear inhibition. Twelve rats were implanted with coated and uncoated neural electrodes. The recording characteristics of polymer-coated electrodes were indistinguishable from that of control electrodes. After 2 weeks, 4 weeks, and 6 weeks post-implantation the rats were perfused and processed using glial fibrillary acidic protein (GFAP) immunohistochemistry. The coated electrodes glial scar was quantified and found to be the same as that induced by non-coated neural electrodes. The prospect of utilizing these nanofiber scaffoldings for drug delivery can now be investigated.
Comparison of Ximelagatran with Warfarin for the Prevention of Venous Thromboembolism after Total Knee Replacement (2003)

The efficacy of oral ximelagatran, administered starting the morning after total knee replacement, was superior to that of warfarin for prevention of venous thromboembolism. Rates of hemorrhagic complications with the two drugs were similar.
Catalytic Properties of Lipopolysaccharide (LPS) Binding Protein (1996)

Lipopolysaccharide (LPS) binding protein (LBP) is a lipid transfer protein that catalyzes transfer of LPS monomers from micelles to a binding site on soluble CD14 (sCD14) and transfer of LPS from LPS.sCD14 complexes to HDL particles. To characterize the first of these two reactions, LPS covalently derivatized with the fluorophore, boron dipyrromethene difluoride (BODIPY), was used to monitor LBP-catalyzed movement of LPS in real time. The fluorescence efficiency of micelles of BODIPY-LPS was low but was strongly increased upon dissolution in detergent or upon binding to sCD14. Spontaneous binding of BODIPY-LPS to sCD14 was very slow but was accelerated by substoichiometric concentration of LBP, and the rate of binding was measured under a variety of conditions. LBP-catalyzed transfer was first order with respect to both sCD14 and LPS concentration, and the apparent Km values were 1 approximately 2 microg/ml for sCD14 and 100 ng/ml for LPS. The maximum turnover number for LBP was approximately 150 molecules of LPS min-1 LBP-1. LBP alone caused a small but measurable increase in the fluorescence of BODIPY-LPS, suggesting that it bound LPS aggregates but did not readily remove LPS monomers. The subsequent addition of sCD14 caused a large fluorescence increase, suggesting transfer of BODIPY-LPS to sCD14. These and other observations suggest that LPS is transferred by an ordered ternary complex reaction mechanism in which LBP transfers LPS monomer from LPS aggregates to sCD14 without dissociating from the LPS aggregate.
Gastrin antagonists in the treatment of gastric cancer (1993)

The polypeptide hormone, gastrin, is known to promote both the in vitro and in vivo growth of human gastric cancer. This proliferative activity has been shown to be mediated by high affinity, membrane-associated receptors. This has led to the development of agents with the ability to antagonise gastrin receptor binding, which have been evaluated for their potential clinical value. Other anti-gastrin therapies have been investigated. As gastrin may act as an autocrine mediator of gastric tumor cell proliferation, anti-secretory agents have been evaluated, as have agents which induce the production of neutralising anti-gastrin antibodies in situ.
Real world requirements for decision support—implications for RDBMS (1995)

No abstract available.
Cardiomyocyte-Restricted Over-Expression of C-Type Natriuretic Peptide Prevents Cardiac Hypertrophy Induced by Myocardial Infarction in Mice (2007)

Over-expression of CNP in cardiomyocytes does not affect I/R-induced infarct size but prevents cardiac hypertrophy induced by MI. Therefore, CNP may represent a potent therapeutic target for the treatment of patients with cardiac hypertrophy induced by myocardial infarction or other aetiology.