gebhart/patrepeval huggingface dataset:
Renal tubular processing of small peptide hormones. (1982)

Reabsorption and/or degradation of proteins or peptides are functions of the proximal tubule. Large polypeptides or proteins are reabsorbed by luminal endocytosis and hydrolyzed by lysosomal enzymes. Our recent studies indicate that small linear peptides are hydrolyzed at the luminal membrane, with reabsorption of metabolites. The renal transport and hydrolysis of radiolabeled Al, All, BKN, oxytocin, glucagon, insulin, and LHRH were studied. Techniques for in vivo microinfusion of surface tubules in rats, arterial infusion in filtering and nonfiltering rat kidneys in vivo, and in vitro microperfusion of isolated rabbit nephron segments were used. Reabsorption of radiolabeled material was measured and the intact peptide or its metabolites were identified and quantified in urine, renal venous blood, bathing medium, and/or collection fluid. In addition, peptides were incubated in the presence of isolated renal membrane preparations to identify a probably cellular site of hydrolysis. The findings indicate that in proximal, but not distal tubules, radiolabeled Al, All, BKN, glucagon, and LHRH are hydrolyzed by brush border enzymes at the luminal membrane, followed by reabsorption of metabolites. In addition, it was found that, similar to the small intestine, the proximal tubule reabsorbed small peptide fragments, which were further degraded intracellurarly, In vivo inhibition studies with excess peptides revealed that hydrolysis is a more specific process than studies with excess peptides revealed that hydrolysis is a more specific process than reabsorption of metabolites. Large or small, complex peptides like insulin, oxytocin, or vasopressin that contain disulfide bridges are not hydrolyzed at the luminal brush border of the proximal tubule. In vivo sequestration and slow degradation of insulin by rat tubules suggest that this peptide is reabsorbed by endocytosis and degraded in lysosomes. Thus, as the molecular complexity or weight of a peptide increases, the mechanism for renal tubular degradation, instead of depending on luminal membrane hydrolysis, may primarily involve endocytosis and lysosomal digestion. This recently described mechanism for hydrolysis and transport of small linear peptides in the proximal nephron is characterized by having a high capacity and is analogous to membrane hydrolysis described for intestinal microvilli. The process may be biologically important to (1) conserve amino acids, (2) inactivate toxic peptides, and (3) help regulate circulating levels of peptide hormones.
Crystallization of Millimeter-Scale Objects with Use of Capillary Forces (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTCrystallization of Millimeter-Scale Objects with Use of Capillary ForcesJoe Tien, Tricia L. Breen, and George M. WhitesidesView Author Information Department of Chemistry and Chemical Biology Harvard University, Cambridge Massachusetts 02138 Cite this: J. Am. Chem. Soc. 1998, 120, 48, 12670–12671Publication Date (Web):November 18, 1998Publication History Received29 June 1998Published online18 November 1998Published inissue 1 December 1998https://pubs.acs.org/doi/10.1021/ja982246yhttps://doi.org/10.1021/ja982246yrapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views460Altmetric-Citations68LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Crystal structure,Crystallization,Crystals,Hydrophobicity,Liquids Get e-Alerts
Association of Vibrio parahaemolyticus Thermostable Direct Hemolysin with Lipid Rafts Is Essential for Cytotoxicity but Not Hemolytic Activity (2009)

Thermostable direct hemolysin (TDH), a major virulence factor of Vibrio parahaemolyticus, induces cytotoxicity in cultured cells. However, the mechanism of TDH's cytotoxic effect including its target molecules on the plasma membrane of eukaryotic cells remains unclear. In this study, we identified the role of lipid rafts, cholesterol- and sphingolipid-enriched microdomains, in TDH cytotoxicity. Treatment of cells with methyl-beta-cyclodextrin (MbetaCD), a raft-disrupting agent, inhibited TDH cytotoxicity. TDH was associated with detergent-resistant membranes (DRMs), and MbetaCD eliminated this association. In contrast, there was no such association between a nontoxic TDH mutant and DRMs. The disruption of lipid rafts neither affected hemolysis nor inhibited Ca(2+) influx into HeLa cells induced by TDH. These findings indicate that the cytotoxicity but not the hemolytic activity of TDH is dependent on lipid rafts. The exogenous and endogenous depletion of cellular sphingomyelin also prevented TDH cytotoxicity, but a direct interaction between TDH and sphingomyelin was not detected with either a lipid overlay assay or a liposome absorption test. Treatment with sphingomyelinase (SMase) at 100 mU/ml disrupted the association of TDH with DRMs but did not affect the localization of lipid raft marker proteins (caveolin-1 and flotillin-1) with DRMs. These results suggest that sphingomyelin is important for the association of TDH with lipid rafts but is not a molecular target of TDH. We hypothesize that TDH may target a certain group of rafts that are sensitive to SMase at a certain concentration, which does not affect other types of rafts.
Security issues in policy routing (2003)

Most routing protocols, including proposed policy routing protocols, focus on environments where detection of an attack after it has taken place is sufficient. The authors explore the design of policy routing mechanisms for sensitive environments where more aggressive preventative measures are mandated. In particular, they detail the design of four secure protocol versions that prevent abuse by cryptographic checks of data integrity. They analyze and compare these schemes in terms of their prepacket processing overhead. It is concluded that preventative security is feasible, although the overhead cost is quite high. Consequently, it is critical that prevention-based schemes coexist with detection-based schemes.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Superscaling in nuclei: A search for a scaling function beyond the relativistic Fermi gas model (2004)

We construct a scaling function $f({\ensuremath{\psi}}^{\ensuremath{'}})$ for inclusive electron scattering from nuclei within the coherent density fluctuation model (CDFM). The latter is a natural extension to finite nuclei of the relativistic Fermi gas model within which the scaling variable ${\ensuremath{\psi}}^{\ensuremath{'}}$ was introduced by Donnelly and collaborators. The calculations show that the high-momentum components of the nucleon momentum distribution in the CDFM and their similarity for different nuclei lead to quantitative description of the superscaling in nuclei. The results are in good agreement with the experimental data for different transfer momenta showing superscaling for negative values of ${\ensuremath{\psi}}^{\ensuremath{'}}$, including those smaller than $\ensuremath{-}1$.
Insulin resistance of glucose response produced by hepatic denervations (1993)

This study investigated the glucose response to insulin infused after hepatic denervation. Hepatic denervations were performed on 13 anesthetized cats at different levels: (i) surgical hepatic anterior plexus denervation, (ii) chemical total hepatic denervation by painting phenol on the tissues around the portal vein, bile duct, common hepatic artery, and hepatic ligaments, and (iii) bilateral vagotomy. Sham denervations were performed on 9 animals. Before denervation and after each performance of denervations, insulin (100 mU/kg, i.v.) was infused. Plasma glucose concentrations were analyzed at 15, 30, 45, and 60 min after insulin infusion. Hepatic anterior plexus denervation produced a significant reduction in insulin effectiveness. Phenol denervation and bilateral vagotomy failed to further significantly alter the level of insulin resistance developed by hepatic anterior plexus denervation. These observations demonstrate that the effect of insulin on glucose regulation is markedly reduced in the absence of hepatic anterior plexus innervation, suggesting that hepatic nerve function is necessary for the normal glucose response to insulin. Furthermore, the hepatic nerves of relevance appear to reach the liver primarily, if not exclusively, by the anterior hepatic plexus.
MIGRATION PATTERNS OF DENDRITIC LEUKOCYTES (1990)

Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, United Kingdom
Protective Efficacy of an AIDS Vaccine, a Single DNA Priming Followed by a Single Booster with a Recombinant Replication-Defective Sendai Virus Vector, in a Macaque AIDS Model (2003)

We previously demonstrated the excellent protective efficacy of DNA priming followed by Gag-expressing Sendai virus (SeV) boosting (DNA prime/SeV-Gag boost vaccine) against a pathogenic simian-human immunodeficiency virus (SHIV89.6PD) infection in macaques. Here we show that we established a practical, safer AIDS vaccine protocol, a single DNA priming followed by a single booster with a recently developed replication-defective F deletion SeV-expressing Gag, and show its protective efficacy against SHIV89.6PD infections.
Differential effects of N -Methyl-D-aspartate receptor blockade on nociceptive somatic and visceral reflexes (1999)

N-methyl-D-aspartate (NMDA) receptors appear to play little part in nociceptive responses evoked by acute stimulation of normal somatic tissues, but rather are involved in hyperalgesic responses after peripheral injury and inflammation. Previous studies from this laboratory have shown important differences in the neural organization of somatic and visceral nociceptive pathways. Here, we have explored the role of NMDA receptors in processing acute visceral noxious input, compared with somatic noxious input. The left ureter was cannulated close to the bladder in adult female Wistar rats anaesthetized with pentobarbitone (50 mg/kg i.p). Graded distentions of the ureter (30 s, 25-80 mmHg) evoked increases in blood pressure. These responses were dose-dependently inhibited by the NMDA receptor ion channel blockers ketamine and memantine (ID50 = 2.4+/-1.6 and 14.5+/-1.3 mg/kg, i.v.), and by the Merz glycine site antagonist Mrz 2/ 576 (ID50 = 0.2+/-0.2 mg/kg). Graded pinch stimuli (30 s, 2-4 N) of one hind-paw evoked similar pressor responses which were not affected by ketamine (up to 10 mg/kg). Similarly, Mrz 2/576 did not affect responses to noxious pinch, whereas memantine (ID50 = 17+/-12 mg/kg) did inhibit responses to pinch stimuli. However, in the dose range used neither ketamine nor Mrz 2/576 inhibited a pressor response of non-nociceptive origin (produced by bilateral carotid occlusion) whereas memantine did. Thus the effects of memantine are likely due to a non-specific cardiovascular effect. These results show that NMDA receptor antagonists inhibit nociceptive reflexes evoked from the normal ureter, and suggest that NMDA receptors are involved in the processing of acute nociceptive inputs from viscera. We conclude that acute stimulation of normal visceral tissue provokes intense responses that recruit neural mechanisms mediated by NMDA receptors. However, in somatic pathways, these mechanisms are recruited only by an enhanced peripheral input such as that produced after injury or inflammation.
«Cette atroce république de la forêt». Les origines du paradigme jivaro (1987)

Taylor Anne-Christine. «Cette atroce république de la forêt». Les origines du paradigme jivaro. In: Gradhiva : revue d'histoire et d'archives de l'anthropologie, n°3, 1987. pp. 3-10.
Screening and elementary excitations in narrow-channel semiconductor microstructures (1985)

The dielectric response of a one-dimensional electron gas occurring in the narrow inversion layers in metal-oxide-semiconductor field-effect transistor (or quantum-well) structures is investigated theoretically. A nonsingular screening function appropriate for dc transport calculations is derived. The plasma frequency in such a system is obtained as an explicit function of wave number. Plasmon dispersion for a lateral two-dimensional superlattice made from such one-dimensional quantum wires is also calculated.
The Evolution of Phosphonate Technology for Corrosion Inhibition (1995)

Abstract The commercialization of phosphonates for cooling water applications ushered in a new era for chemical treatment by the service companies. Introduced in the late 1960's, they remain the mainstay of programs utilized in areas ranging from HVAC to heavy industrial applications in steel mills. The longevity of this family of compounds is due to their effectiveness as calcium carbonate threshold agents and apparent activity as ferrous metal corrosion inhibitors. The universal acceptance of phosphonates in cooling water programs has inadvertently resulted in generalized applications of the materials. In reality each phosphonate compound possesses properties that distinguish them for specific applications. The purpose of this paper is to highlight the strengths of phosphonates incorporated into cooling water formulations. Information will be presented outlining activity for commercially available phosphonates including a new phosphonate, POCA, using bench and process tests.
Live‐cell analysis of cell penetration ability and toxicity of oligo‐arginines (2007)

Cell penetrating peptides (CPPs) are useful tools to deliver low-molecular-weight cargoes into cells; however, their mode of uptake is still controversial. The most efficient CPPs belong to the group of arginine-rich peptides, but a systematic assessment of their potential toxicity is lacking. In this study we combined data on the membrane translocation abilities of oligo-arginines in living cells as a function of their chain length, concentration, stability and toxicity. Using confocal microscopy analysis of living cells we evaluated the transduction frequency of the L-isoforms of oligo-arginines and lysines and then monitored their associated toxicity by concomitant addition of propidium iodide. Whereas lysines showed virtually no transduction, the transduction ability of arginines increased with the number of consecutive residues and the peptide concentration, with L-R9 and L-R10 performing overall best. We further compared the L- and D-R9 isomers and found that the D-isoform always showed a higher transduction as compared to the L-counterpart in all cell types. Notably, the transduction difference between D- and L-forms was highly variable between cell types, emphasizing the need for protease-resistant peptides as vectors for drug delivery. Real-time kinetic analysis of the D- and L-isomers applied simultaneously to the cells revealed a much faster transduction for the D-variant. The latter underlies the fact that the isomers do not mix, and penetration of one peptide does not perturb the membrane in a way that gives access to the other peptide. Finally, we performed short- and long-term cell viability and cell cycle progression analyses with the protease-resistant D-R9. Altogether, our results identified concentration windows with low toxicity and high transduction efficiency, resulting in fully bioavailable intracellular peptides.
The Nephroblastoma Overexpressed Gene (NOV/ccn3) Protein Associates with Notch1 Extracellular Domain and Inhibits Myoblast Differentiation via Notch Signaling Pathway (2002)

We demonstrate a novel interaction of the nephroblastoma overexpressed gene (NOV), a member of the CCN gene family, with the Notch signaling pathway. NOV associates with the epidermal growth factor-like repeats of Notch1 by the CT (C-terminal cysteine knot) domain. The promoters of HES1 and HES5, which are the downstream transducers of Notch signaling, were activated by NOV. Expressions of NOV and Notch1 were concomitant in the presomitic mesoderm and later in the myocytes and chondrocytes, suggesting their synergistic effects in mesenchymal cell differentiation. In C2/4 myogenic cells, elevated expression of NOV led to down-regulation of MyoD and myogenin, resulting in inhibition of myotube formation. These results indicate that NOV-Notch1 association exerts a positive effect on Notch signaling and consequently suppresses myogenesis.
Acute Platelet Inhibition With Abciximab Does Not Reduce In-Stent Restenosis (2000)

We read with great interest the recent article by the Evaluation of ReoPro and Stenting to Eliminate Restenosis (ERASER) Investigators, in which it was reported that potent platelet inhibition with abciximab does not reduce in-stent restenosis. 1 Abciximab is an effective antithrombotic agent because of its ability to bind to glycoprotein IIb/IIIa (IIb/3) and to inhibit platelet aggregation. Abciximab also binds to a related integrin, v3, which is also known as the vitronectin receptor. The functions of this receptor include cell adhesion, proliferation, and migration and platelet-mediated thrombin generation. Thus, abciximab is expected to provide platelet-mediated effects and v3-mediated effects in vivo. 2 Previously, we investigated changes in coagulation and platelet activation in the coronary circulation induced by stent implantation. 3 Both aspirin and ticlopidine were administered to patients before stent implantation. Blood samples were drawn from the coronary sinus immediately before, immediately after, and 4 and 24 hours after stent implantation. Plasma levels of prothrombin fragment 12 (F12) and thrombin-antithrombin III complex (TAT), which are markers of coagulation activation, and levels of -thromboglobulin (-TG) and platelet factor 4 (PF4), which are markers of platelet disruption and activation, were measured. We found that F12 and TAT levels in blood from the coronary sinus increased significantly 24 hours after stent implantation (F12, from 0.730.05 to 1.000.10 ng/mL; TAT, from 5.010.64 to 10.72.26 ng/mL). However, no significant changes in -TG and PF4 levels were observed after stent implantation (-TG, from 60.18.6 to 63.89.2 ng/mL; PF4, from 27.65.0 to 19.96.3 ng/mL).
Imiquimod 5% Cream is a Safe and Effective Self-Applied Treatment for Anogenital Warts — Results of an Open-Label, Multicentre Phase IIIB Trial (2001)

Our objective was to determine the efficacy and safety of imiquimod 5% cream in the treatment of external genital/perianal warts in an open-label Phase IIIB trial. Patients applied imiquimod 5% cream 3 times per week, for up to 16 weeks. Those who cleared their warts were monitored during a 6-month follow-up period. If their warts recurred, or new warts developed during this time, patients could be re-treated for up to 16 additional weeks. Patients who experienced partial clearance during the initial treatment period entered an extended treatment period of up to an additional 16 weeks. A total of 943 patients from 114 clinic sites in 20 countries participated in this study. Complete clinical clearance was observed in 451/943 (47.8%) patients (intent-to-treat (ITT) analysis) during the initial treatment period, with clearance in an additional 52 (5.5%) patients during the extended treatment period beyond 16 weeks. The overall clearance rate for the combined treatment periods was 53.3%. In a treatment failure analysis, the overall clearance rate was 65.5%; a greater proportion of female patients (75.5%) experienced complete clearance than male patients (56.9%). Low recurrence rates, of 8.8% and 23.0%, were observed at the end of the 3- and 6-month follow-up periods, respectively. The sustained clearance rates (patients who cleared during treatment and remained clear at the end of the follow-up period) after 3 and 6 months were 41.6% and 33.0% (ITT analysis), respectively. Local erythema occurred in 67% of patients. In the majority of patients local skin reactions were of mild to moderate severity. In conclusion, imiquimod 5% cream is an effective self-applied treatment for external genital/perianal warts when applied for up to 16 weeks and is well tolerated for up to 32 weeks.
Specific Nucleotide Binding and Rebinding to Individual DNA Polymerase Complexes Captured on a Nanopore (2009)

Nanoscale pores are a tool for single molecule analysis of DNA or RNA processing enzymes. Monitoring catalytic activity in real time using this technique requires that these enzymes retain function while held atop a nanopore in an applied electric field. Using an alpha-hemolysin nanopore, we measured the dwell time for complexes of DNA with the Klenow fragment of Escherichia coli DNA polymerase I (KF) as a function of the concentration of deoxynucleoside triphosphate (dNTP) substrate. We analyzed these dwell time measurements in the framework of a two-state model for captured complexes (DNA-KF binary and DNA-KF-dNTP ternary states). Average nanopore dwell time increased without saturating as a function of correct dNTP concentration across 4 orders of magnitude. This arises from two factors that are proportional to dNTP concentration: (1) The fraction of complexes that are in the ternary state when initially captured predominantly affects dwell time at low dNTP concentrations. (2) The rate of binding and rebinding of dNTP to captured complexes affects dwell time at higher dNTP concentrations. Thus there are two regimes that display a linear relationship between average dwell time and dNTP concentration. The transition from one linear regime to the other occurs near the equilibrium dissociation constant (K(d)) for dNTP binding to KF-DNA complexes in solution. We conclude from the combination of titration experiments and modeling that DNA-KF complexes captured atop the nanopore retain iterative, sequence-specific dNTP binding, as required for catalysis and fidelity in DNA synthesis.
Structural similarity among Escherichia coli FtsW and RodA proteins and Bacillus subtilis SpoVE protein, which function in cell division, cell elongation, and spore formation, respectively (1989)

The Escherichia coli cell division gene ftsW (2 min) was cloned and sequenced. It encodes a hydrophobic protein(s) with 414 and/or 384 amino acid residues. The deduced amino acid sequence and the hydropathy profile of the protein showed high homology with those of the E. coli RodA protein functioning in determination of the cell shape and the Bacillus subtilis SpoVE protein functioning in spore formation. Probably similar functional membrane proteins are involved in these three cell cycle process.
Continuous Dopaminergic Stimulation in Cranial Dystonia (1988)

Meige's disease is a distressing complaint, the treatment of which often poses a challenge to the neurologist. The patient described here had blepharospasm-oromandibular dystonia, which responded transiently to oral lisuride. On three occasions, drug holidays successfully restored efficacy but thereafter further trials proved fruitless. Continuous subcutaneous lisuride administration in 0.35 mg doses per day, by means of a portable infusion pump, led to sustained improvement for 7 months. No major side effects were observed. Our findings suggest that this treatment deserves further trials.
Anti-hypoxia and anti-oxidation effects of aminophylline on human with acute high-altitude exposure. (2007)

Aminophylline has significant anti-hypoxia and anti-oxidation effects at high altitude.