gebhart/patrepeval huggingface dataset:
Pharmacological effects of the non‐competitive NMDA antagonist CNS 1102 in normal volunteers. (1994)

1. Non-competitive antagonists at the glutamatergic N-methyl D-aspartate receptor significantly reduce the volume of ischaemic cerebral infarction in animals and are potential agents for the treatment of acute stroke in humans. 2. CNS 1102, a novel non-competitive NMDA antagonist, was administered as a 15 min intravenous infusion to healthy male volunteers in a double-blind, placebo-controlled, dose-ranging study. This was the first administration to man. 3. Clinically significant sedation, increased mean arterial pressure and pulse rate were seen at doses of 30 micrograms kg-1 and above. Symptoms of sedation and central nervous excitation became unacceptable for conscious individuals at doses of 45 micrograms kg-1 and above. 4. Rapid onset of central nervous system effects after administration is in keeping with rapid distribution of CNS 1102 to brain. Steady state volume of distribution was large (444 l) and terminal elimination half-life from plasma was approximately 4 h. 5. Pharmacokinetic properties are favourable for a potential neuroprotective therapy. The maximum tolerated dose for conscious individuals was 30 micrograms kg-1 given intravenously over 15 min. Further assessment of CNS 1102 should seek methods of drug administration which maximise administered dose with minimal side effects.
Expression of an additional cathelicidin antimicrobial peptide protects against bacterial skin infection (2005)

Cathelicidin antimicrobial peptides are effectors of innate immune defense in mammals. Humans and mice have only one cathelicidin gene, whereas domesticated mammals such as the pig, cow, and horse have multiple cathelicidin genes. We hypothesized that the evolution of multiple cathelicidin genes provides these animals with enhanced resistance to infection. To test this, we investigated the effects of the addition of cathelicidins by combining synthetic cathelicidin peptides in vitro, by producing human keratinocytes that overexpress cathelicidins in culture, or by producing transgenic mice that constitutively overexpress cathelicidins in vivo. The porcine cathelicidin peptide PR-39 acted additively with human cathelicidin LL-37 to kill group A Streptococcus (GAS). Lentiviral delivery of PR-39 enhanced killing of GAS by human keratinocytes. Finally, transgenic mice expressing PR-39 under the influence of a K14 promoter showed increased resistance to GAS skin infection (50% smaller necrotic ulcers and 60% fewer surviving bacteria). Similarly constructed transgenic mice designed to overexpress their native cathelicidin did not show increased resistance. These findings demonstrate that targeted gene transfer of a xenobiotic cathelicidin confers resistance against infection and suggests the benefit of duplication and divergence in the evolution of antimicrobial peptides.
Product Configuration View to Software Product Families (2001)

Development and management of software product families is an emerging and important area of software engineering, whereas product configuration of traditional, i.e., mechanical and electronic, product families has a slightly longer history as a specific area of research and business. This paper describes work in progress on the management of configurable software product families. Solutions to modelling and managing such software products are sought from experiences with traditional products.
New experimental and clinical data on the efficacy of pharmacological magnesium infusions in cerebral infarcts. (1998)

Multiple metabolic processes have been identified within the critically perfused ischaemic penumbra on the margins of cerebral infarcts. Intervention in many of these processes has been neuroprotective, notably blockade of glutamate receptors such as the N-methyl D-aspartate (NMDA) receptor. Magnesium may act as a neuroprotective agent through vascular effects (increasing regional cerebral blood flow to ischaemic tissue, anticonstrictor effects against vascular mediators, vasodilatation of the cerebral circulation) or neuronal effects. Neuronal effects include block of the NMDA receptor ion channel, calcium antagonism at voltage-gated channels, enhanced buffering of intracellular calcium ions, and enhanced regeneration of adenosine triphosphate. Magnesium infusions of sulphate or chloride salts are significantly neuroprotective in standard animal focal cerebral ischaemia models, with benefits being evident at serum concentrations attainable in humans. Mg systemic infusion causes rises in cerebrospinal fluid and brain magnesium concentrations. Magnesium is also neuroprotective in other models of cerebral ischaemia. Three clinical trials in acute stroke have involved just over 100 patients. No adverse effects have been observed, and trends favouring magnesium treatment have been seen. A large multicentre clinical trial testing the efficacy of magnesium sulphate is underway, and should report within 4 years.
Spontaneous Vesicle Formation in Aqueous Mixtures of Single-Tailed Surfactants (1989)

Spontaneous, single-walled, equilibrium vesicles can be prepared from aqueous mixtures of simple, commercially available, single-tailed cationic and anionic surfactants. Vesicle size, surface charge, or permeability can be readily adjusted by varying the ratio of anionic to cationic surfactant. Vesicle formation apparently results from the production of anion-cation surfactant pairs that then act as double-tailed zwitterionic surfactants. These vesicles are quite stable in comparison to conventional vesicles prepared by mechanical disruption of insoluble liquid crystalline dispersions.
Regulation of transbilayer plasma membrane phospholipid asymmetry (2003)

Lipids in biological membranes are asymmetrically distributed across the bilayer; the amine-containing phospholipids are enriched on the cytoplasmic surface of the plasma membrane, while the choline-containing and sphingolipids are enriched on the outer surface. The maintenance of transbilayer lipid asymmetry is essential for normal membrane function, and disruption of this asymmetry is associated with cell activation or pathologic conditions. Lipid asymmetry is generated primarily by selective synthesis of lipids on one side of the membrane. Because passive lipid transbilayer diffusion is slow, a number of proteins have evolved to either dissipate or maintain this lipid gradient. These proteins fall into three classes: 1) cytofacially-directed, ATP-dependent transporters ("flippases"); 2) exofacially-directed, ATP-dependent transporters ("floppases"); and 3) bidirectional, ATP-independent transporters ("scramblases"). The flippase is highly selective for phosphatidylserine and functions to keep this lipid sequestered from the cell surface. Floppase activity has been associated with the ABC class of transmembrane transporters. Although they are primarily nonspecific, at least two members of this class display selectivity for their substrate lipid. Scramblases are inherently nonspecific and function to randomize the distribution of newly synthesized lipids in the endoplasmic reticulum or plasma membrane lipids in activated cells. It is the combined action of these proteins and the physical properties of the membrane bilayer that generate and maintain transbilayer lipid asymmetry.
Primary dexamethasone treatment of multiple myeloma (1992)

Intermittent courses of dexamethasone (DEX) were administered to 112 consecutive, previously untreated patients with multiple myeloma (MM). Using criteria based on a 75% or greater reduction of calculated tumor mass, the overall response rate was 43%. Among comparable patients, response rate were approximately 15% less than those observed previously with vincristine-doxorubicin by continuous infusion with intermittent DEX (VAD) and similar to those with melphalan-prednisone. The projected survival times with VAD or DEX were similar. Results indicated that DEX accounted for most of the plasma cell reduction achieved with VAD. Serious complications occurred in 27% of patients treated with VAD, but in only 4% of those who received DEX. In view of the similar outcome with fewer serious complications, DEX provided a simple, effective, and safe primary treatment for a large fraction of patients with MM. Patients who appear most likely to benefit include those with hypercalcemia or pancytopenia, or who require simultaneous radiotherapy for a pathologic fracture.
Transgenic Cre recombinase expression in germ cells and early embryogenesis directs homogeneous and ubiquitous deletion of loxP‐flanked gene segments (1998)

We report on the establishment of a transgenic mouse line expressing Cre recombinase under control of the c-kit promoter. Expression of Cre recombinase was only observed in late spermatogenesis and oogenesis, however, Cre-mediated deletion of floxed gene segments occurred at this stage as well as in early embryogenesis. As a consequence of this, a chimeric distribution of loxed alleles was found in a large fraction of these mice. The chimerism was very homogeneous in different organs and tissues of the same individual but varied between different individual offspring. The potential uses for this mouse line are discussed.
Rhythmic Expression of timeless : A Basis for Promoting Circadian Cycles in period Gene Autoregulation (1995)

The clock gene timeless (tim) is required for circadian rhythmicity in Drosophila. The accumulation of tim RNA followed a circadian rhythm, and the phase and period of the tim RNA rhythm were indistinguishable from those that have been reported for per. The tim RNA oscillations were found to be dependent on the presence of PER and TIM proteins, which demonstrates feedback control of tim by a mechanism previously shown to regulate per expression. The cyclic expression of tim appears to dictate the timing of PER protein accumulation and nuclear localization, suggesting that tim promotes circadian rhythms of per and tim transcription by restricting per RNA and PER protein accumulation to separate times of day.
Triggering of neoplastic B cells via surface IgM and the cell surface antigens CD20 and CDw40. Responses differ from normal blood B cells and are restricted to certain morphologic subsets (1988)

By raising monoclonal antibodies (MAbs) against B cells, a number of cell surface molecules have recently been identified which after binding by their specific antibody can trigger B cells, either alone or in co-operation with antibodies to surface immunoglobulin (sIg). The anti-CD20 (Bp35) MAb IF5 can deliver a strong activation signal to resting normal B cells, and the anti-CDw40 (Bp50) MAb G28-5 can promote activated G1 B cells to enter S phase. These antibodies were tested for their functional effects in vitro on suspended cells from 17 follicle-center-cell (FCC) lymphomas, 5 cases of chronic lymphatic B-cell leukemia (B-CLL) and 8 cases of various histological types. Changes in cellular volume, RNA and DNA synthesis were compared with the results obtained with a polyclonal anti-mu [F(ab')2] antiserum, a MAb to surface IgM (AF6), 12-O-tetradecanoyl-phorbol-13-acetate (TPA) and B-cell growth factor (low-molecular-weight BCGF). Our data reveal differences in the requirements for triggering of various B-cell subsets: cells from CLL responded strongly to TPA but not to anti-mu, which is a potent stimulator not only of normal B cells but also of cells from individual cases of FCC lymphomas. Our observations suggest that the differentiation stage of B-CLL cells is distinct from that of small resting B cells from peripheral blood. Centrocytic lymphomas could not be activated by any of the reagents. CD20-mediated triggering was seen in neoplastic B cells from only 4 of 30 cases, indicating that most B-cell neoplasias were not responsive to this activation pathway. In contrast, the anti-CDw40 MAb consistently stimulated DNA synthesis together with anti-mu or TPA in cells from FCC lymphomas, but not from CLL. Together, these results suggest that activation in different neoplastic B-cell subsets depends on distinct signal transduction mechanisms.
First IETF internet audiocast (1992)

article Free Access Share on First IETF internet audiocast Authors: Stephen Casner View Profile , Stephen Deering View Profile Authors Info & Claims ACM SIGCOMM Computer Communication ReviewVolume 22Issue 3July 1992 pp 92–97https://doi.org/10.1145/142267.142338Published:01 July 1992Publication History 132citation305DownloadsMetricsTotal Citations132Total Downloads305Last 12 Months69Last 6 weeks7 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my Alerts New Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteeReaderPDF
Hairless triggers reactivation of hair growth by promoting Wnt signaling (2005)

The mammalian hair cycle involves periodic regeneration of a tiny organ, the hair follicle, through a stem-cell-mediated process. The Hairless (Hr) gene encodes a nuclear receptor corepressor (HR) that is essential for hair follicle regeneration, but its role in this process is unknown. Here, we demonstrate that transgenic expression of HR in progenitor keratinocytes rescues follicle regeneration in Hr(-/-) mice. We show that expression of Wise, a modulator of Wnt signaling, is repressed by HR in these cells, coincident with the timing of follicle regeneration. This work links HR and Wnt function, providing a model in which HR regulates the precise timing of Wnt signaling required for hair follicle regeneration.
Highly Efficient Green Phosphorescent Organic Light‐Emitting Diodes Based on CuI Complexes (2004)

Mononuclear Cu I complexes with mixed ligands are used to fabricate green phosphorescent organic light‐emitting diodes. The electroluminescence (EL) maximum at 524 nm coincides well with its photoluminescent (PL) spectrum in poly(methyl methacrylate) film (see Figure). A maximum current efficiency of 10.5 cd A –1 at 105 cd m –2 and a maximum brightness up to 1663 cd m –2 are demonstrated.
Novel Ring Transformation Reactions and Their Applications to the Syntheses of Potential Anticancer Heterocyclic Compounds (1984)

Novel heterocyclic r i n g transformation reactions developed recently i n our laboratory are described.They include ~y r i m i d i n e t o oyrimidine, pyrimidine t o p y r idine transformations.Also discussed a r e novel one-sten nrocedures f o r conversion o f 1,3-dimethyluracil d e r i v a t i v e s i n t o the pyrido[2,3-dlpyrimidine system.Some a p p l ic a t i o n s o f t h e s e novel reactions t o the sytheses o f compounds o f b i o l o p i c a l i n t e r e s t a r e a l s o described.2 I n 1975 we synthesized the C-nucleoside, 5-(8-D-ribofuranosyl)isocytosine (9-isocytidine, Fig.I ) , as an i s o s t e r e o f c y t i d i n e and 5-azacytidine.The l a t t e r , synthesized o r i g i n a l l y by Piskala and sorm3 i n 1964, was l a t e r i s o l a t e d from Streptomyces ladakamus as a nucleoside a n t i b i o t i ~. ~ 5-Pzac y t i d i n e i s known t o be of value i n the treatment o f human acute myelopenous leukemia r e s i s t a n t t o arabinosylcytosine ( a r a -c ) , ~ and has shown some a c t i v i t y i n p a t i e n t s w i t h breast melanoma,6 and colon cancer.6I n almost a l l c l i n i c a l cases, however, undesirable side e f f e c t s o f t h i s a n t i b i o t i c have been o b s e r ~e d .~-~ Moreover, 5-azacytidine i s r e l a t i v e l y unstable i n aqueous media and i s very susceptible t o enzymatic hydrolysis forminp, eventually, r i b o s y l d e r i v a t i v e s of Narnidinourea o r N-formylbiuret and biuret.' 9-Isocytidine was therefore prenared as a s t a b l e anal o g o f 5-azacytidine.This synthetic C-nucleoside exhibited
PEX11α Is Required for Peroxisome Proliferation in Response to 4-Phenylbutyrate but Is Dispensable for Peroxisome Proliferator-Activated Receptor Alpha-Mediated Peroxisome Proliferation (2002)

The PEX11 peroxisomal membrane proteins promote peroxisome division in multiple eukaryotes. As part of our effort to understand the molecular and physiological functions of PEX11 proteins, we disrupted the mouse PEX11alpha gene. Overexpression of PEX11alpha is sufficient to promote peroxisome division, and a class of chemicals known as peroxisome proliferating agents (PPAs) induce the expression of PEX11alpha and promote peroxisome division. These observations led to the hypothesis that PPAs induce peroxisome abundance by enhancing PEX11alpha expression. The phenotypes of PEX11alpha(-/-) mice indicate that this hypothesis remains valid for a novel class of PPAs that act independently of peroxisome proliferator-activated receptor alpha (PPARalpha) but is not valid for the classical PPAs that act as activators of PPARalpha. Furthermore, we find that PEX11alpha(-/-) mice have normal peroxisome abundance and that cells lacking both PEX11alpha and PEX11beta, a second mammalian PEX11 gene, have no greater defect in peroxisome abundance than do cells lacking only PEX11beta. Finally, we report the identification of a third mammalian PEX11 gene, PEX11gamma, and show that it too encodes a peroxisomal protein.
Role of alpha v integrins during angiogenesis. (2000)

Angiogenesis depends on specific molecular interactions between vascular cells and components of the extracellular matrix. This review focuses on the recent advances in the understanding of the mechanism of action of integrins and integrin antagonists during angiogenesis. For example, angiogenesis induced with vascular endothelial growth/permeability factor but not with basic fibroblast growth factor (bFGF) depends on integrin avb5 and Src kinase activity. In contrast, bFGF-induced angiogenesis requires integrin avb3 and functions independently of Src. Recent studies document a role for integrins and growth factor regulation of Src family kinases during angiogenesis. We also discuss the effect of av integrin antagonists on angiogenesis during tumor growth, inflammatory disease, and retinopathy and summarize recent clinical progress in using av integrin antagonists.
Characterization of the hormone binding site of natriuretic peptide receptor‐C (1995)

The hormone binding site of rat and human natriuretic peptide clearance receptor (NPR-C), a single transmembrane receptor, has been further refined by mutagenesis. In addition to residue 188 (rat Ala, human Ile), which completely inverts the pharmacology of the rat and human receptors [Engel et al. (1994) J. Biol. Chem. 269, 17005-17008], we report a second key residue at position 205 (rat Tyr, human Asn) which modulates affinity to a limited number of ligands. Orthologous mutation of both residues results in tighter binding for human and weaker binding for rat NPR-C. The ligand binding fold of the receptor is formed by at least the first half of the extracellular domain containing two intramolecular disulfide loops, with the two affinity-modulating residues 188 and 205 in the second loop.
Membrane Permeable Fluorogenic Rhodamine Substrates for Selective Determination of Cathepsin L (1992)

The dipeptidyl rhodamine diamide substrates (Z-Phe-Arg)2-R110 and (Z-Arg-Arg)2-R110 are 820- and 360-fold more selective for cathepsin L than for cathepsin B allowing a sensitive determination of cathepsin L activity in the presence of high activity of cathepsin B. The results obtained with cell lysates suggest that the cysteine proteinase activity of vital macrophages detected by flow cytometry with these substrates is mainly due to cathepsin L.
Subunit Rotavirus Vaccine Administered Parenterally to Rabbits Induces Active Protective Immunity (1998)

Virus-like particles (VLPs) are being evaluated as a candidate rotavirus vaccine. The immunogenicity and protective efficacy of different formulations of VLPs administered parenterally to rabbits were tested. Two doses of VLPs (2/6-, G3 2/6/7-, or P[2], G3 2/4/6/7-VLPs) or SA11 simian rotavirus in Freund's adjuvants, QS-21 (saponin adjuvant), or aluminum phosphate (AlP) were administered. Serological and mucosal immune responses were evaluated in all vaccinated and control rabbits before and after oral challenge with 10(3) 50% infective doses of live P[14], G3 ALA lapine rotavirus. All VLP- and SA11-vaccinated rabbits developed high levels of rotavirus-specific serum and intestinal immunoglobulin G (IgG) antibodies but not intestinal IgA antibodies. SA11 and 2/4/6/7-VLPs afforded similar but much higher mean levels of protection than 2/6/7- or 2/6-VLPs in QS-21. The presence of neutralizing antibodies to VP4 correlated (P < 0.001, r = 0.55; Pearson's correlation coefficient) with enhanced protection rates, suggesting that these antibodies are important for protection. Although the inclusion of VP4 resulted in higher mean protection levels, high levels of protection (87 to 100%) from infection were observed in individual rabbits immunized with 2/6/7- or 2/6-VLPs in Freund's adjuvants. Therefore, neither VP7 nor VP4 was absolutely required to achieve protection from infection in the rabbit model when Freund's adjuvant was used. Our results show that VLPs are immunogenic when administered parenterally to rabbits and that Freund's adjuvant is a better adjuvant than QS-21. The use of the rabbit model may help further our understanding of the critical rotavirus proteins needed to induce active protection. VLPs are a promising candidate for a parenterally administered subunit rotavirus vaccine.
ROLE OF CALCIUM IN AMELIORATION OF COPPER PHYTOTOXICITY FOR CITRUS (1993)

Excessive application of Cu to Florida citrus has resulted in accumulation of Cu, causing Cu toxicity. Maintaining soil pH levels at 6.5 to 7.0 has been recommended to minimize the Cu toxicity problem. In this study, the role of Ca, independent of pH, on Cu toxicity was investigated. Cleopatra mandarin and rough lemon rootstock seedlings were grown in Myakka sand (sandy, siliceous, hyperthermic, Aeric Haploquods) treated with a factorial combination of four Cu rates (0, 50, 100, and 200 mg Cu/kg), two Ca sources (CaCO3 and CaSO4), and four Ca rates (0, 200, 400, and 800 mg Ca/kg). Increasing the rate of Ca from 0 to 800 mg/kg increased the soil pH (1:1, soil:water) by 1.5 unit and decreased the pH by 0.3 unit when using CaCO3 and CaSO4, respectively. Top and root growth were greater for seedlings grown in CaCO3- compared with CaSO4- amended soil. Increasing rates of Ca application, as either CaCO3 or CaSO4, increased top and root growth of both rootstocks at some Cu rates. The effects of increasing rates of Cu on top and root weights in the absence of Ca amendment (i.e., “pure-effect” of Cu) were much greater on Cleopatra mandarin than on rough lemon rootstock. Fibrous root Cu content for both rootstocks was highly correlated with soil Cu extractable by Mehlich 3 (r2 = 0.883 to 0.891) and with root weight (r2 = 0.256 to 0.521). Increasing rates of Ca, applied either as CaCO3 or CaSO4, significantly decreased concentrations of Cu in the fibrous roots. The results demonstrate that increased Ca availability in the rooting environment ameliorates the effects of Cu phytotoxicity. The concentration of Cu in fibrous roots is a better index of Cu phytotoxicity than is that in the leaves.