gebhart/patrepeval huggingface dataset:
A Constrained Diketopiperazine as a New Scaffold for the Synthesis of Peptidomimetics (1998)

As a new scaffold for peptidomimetic synthesis, a highly constrained bifunctional diketopiperazine, 4, has been prepared by smooth N-alkylation with tert-butyl bromoacetate. As a first application, we describe herein the synthesis of new peptidomimetics of the Arg-Gly-Asp (RGD) sequence. The product 30, which shows a selective platelet-aggregation inhibiting activity, can be used as a lead for the preparation of more potent products.
Correction to Fast Translocation of Proteins through Solid State Nanopores (2013)

ADVERTISEMENT RETURN TO ISSUEPREVAddition/CorrectionORIGINAL ARTICLEThis notice is a correctionCorrection to Fast Translocation of Proteins through Solid State NanoporesCalin Plesa, Stefan W. Kowalczyk, Ruben Zinsmeester, Alexander Y. Grosberg, Yitzhak Rabin, and Cees Dekker*Cite this: Nano Lett. 2013, 13, 7, 3445Publication Date (Web):June 5, 2013Publication History Published online5 June 2013Published inissue 10 July 2013https://doi.org/10.1021/nl4019269Copyright © 2013 American Chemical SocietyRequest reuse permissions This publication is free to access through this site. Learn MoreArticle Views834Altmetric-Citations5LEARN 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 InReddit PDF (101 KB) Get e-Alertsclose Get e-Alerts
Hemolytic and antimicrobial activities of the twenty-four individual omission analogs of melittin (1991)

Although melittin's hemolytic activity has been extensively studied, the orientation of membrane-bound melittin remains uncertain. We have investigated the effect of individually omitted amino acid residues on melittin's activity and related these results to the existing models of melittin-membrane interaction. The extent of hemolysis of the omission analogues closely followed the four known conformational regions of melittin: omission of any of the residues making up the two alpha-helical regions decreased the hemolytic activity relative to melittin, while omission of any of the residues making up the "hinge" or the C-terminal regions had little or no effect. Our results correlate best with a proposed model in which melittin initially forms "holes" in the membrane, resulting in an initial rapid loss of hemoglobin; the membrane-bound melittin is then internalized into the membrane, resulting in a later slow phase of hemoglobin loss. It was also found that induced structural effects caused by peptide-lipid interactions could be studied by using RP-HPLC, with an excellent correlation found between the retention times of the individual omission analogues and their hemolytic activities.
Anti‐Human Immunodeficiency Virus (HIV) Activity, Safety, and Pharmacokinetics of Adefovir Dipivoxil (9‐[2‐(bis‐pivaloyloxymethyl)‐phosphonylmethoxyethyl]adenine) in HIV‐Infected Patients (1997)

A randomized, double-blind, placebo-controlled, dose-escalation study of adefovir dipivoxil, an oral prodrug of adefovir, was conducted in 36 human immunodeficiency virus (HIV)-infected subjects to evaluate its anti-HIV activity, safety, and pharmacokinetics. Subjects received placebo or one of three dosages of adefovir dipivoxil daily for 14 days. Median decreases in serum p24 antigen of 31% (P = .02), 25% (P = .31), and 30% (P = .01) occurred in each drug-treated group, respectively, compared with an increase of 17% in the placebo group. Median decreases in serum HIV RNA of 0.4-0.6 log10 copies/mL occurred in the drug-treated groups (P = .03), compared with no change in the placebo group. Gastrointestinal complaints and reversible liver transaminase elevations were the most frequently noted adverse events. Decreases in serum free carnitine occurred in each drug-treated group during treatment. After 14 days of dosing, adefovir dipivoxil demonstrated anti-HIV activity and was best tolerated at the lowest dosage studied, 125 mg daily.
Effect of the Support on Structure of the Multi-Walled Carbon Nanotubes Grown By CCVD over Nickel Nanoparticles (2017)

Effect of the support and preparation method of the Ni/CaO and Ni/CaCO 3 impregnated catalysts on the morphology, diameters and growth mechanisms of the MWCNTs grown from ethylene by CCVD synthesis were studied. It was found that the interactions between the support and Ni nanoparticles in both cases are mainly weak and the growth mechanism of the majority of the carbon nanotubes is the "tip-growth". The structure of the nanotubes produced using different catalysts was, however, significantly different. Use of the Ni/CaO catalyst results in the formation of two types of the MWCNTs on the basis of the diameters. At the Ni/CaCO 3 , the formation of the MWCNTs and chain-like carbons fibers was observed. The differences in the morphology and diameters related to the distinct chemical transformation of the support and active phase of the catalyst during the catalyst preparation and reduction, as well as during synthesis of the nanotubes.
Vitamin K antagonism of coumarin anticoagulation. A dehydrogenase pathway in rat liver is responsible for the antagonistic effect (1986)

In the liver, it appears that there are two different pathways for vitamin K reduction. One pathway is irreversibly inhibited by coumarin anticoagulant drugs. The other pathway has been shown in the present study to be composed of enzymes that are not effected by physiological 'in vivo' concentrations of these drugs. This pathway appears to be responsible for the antidotal effect of vitamin K in overcoming coumarin poisoning. In rat liver the pathway has been shown to be composed of DT-diaphorase (EC.1.6.99.2) and a microsomal dehydrogenase(s). The activity of the microsomal dehydrogenase(s) was 3.6-fold higher with NADH than with NADPH present in the test system. It appears that this enzyme is the physiologically important enzyme in the pathway. In contrast with DT-diaphorase, this enzyme(s) is shown to be tightly associated with the mirosomal membrane. The enzyme(s) is not identical with either of the quinone-reducing enzymes cytochrome P-450 reductase or cytochrome-b5 reductase. Our data thus postulate the existence of an as-yet-unidentified microsomal dehydrogenase that appears to have an important function in the pathway.
GaAs Injection Laser with Novel Mode Control and Switching Properties (1965)

The effects of nonuniform current densities on the properties of GaAs injection lasers are investigated. The structure studied is an injection laser with a channel etched on the p side of the junction parallel to the reflecting ends. It is found that the threshold current is higher for nonuniform currents than for uniform currents. The mode in which the laser oscillates depends on the distribution of current. A simple model of the transition and the energy vs density of states for the semiconductor is presented to explain these effects. Bistable operation of the structure has been observed.
Stress-induced interleukin-6 release in mice is mast cell-dependent and more pronounced in Apolipoprotein E knockout mice (2003)

The present findings indicate that acute stress leads to mast cell-dependent serum IL-6 increase that may help explain stress-related coronary inflammation.
Different from the HIV Fusion Inhibitor C34, the Anti-HIV Drug Fuzeon (T-20) Inhibits HIV-1 Entry by Targeting Multiple Sites in gp41 and gp120 (2005)

Fuzeon (also known as T-20 or enfuvirtide), one of the C-peptides derived from the HIV-1 envelope glycoprotein transmembrane subunit gp41 C-terminal heptad repeat (CHR) region, is the first member of a new class of anti-HIV drugs known as HIV fusion inhibitors. It has been widely believed that T-20 shares the same mechanism of action with C34, another C-peptide. The C34 is known to compete with the CHR of gp41 to form a stable 6-helix bundle (6-HB) with the gp41 N-terminal heptad repeat (NHR) and prevent the formation of the fusogenic gp41 core between viral gp41 NHR and CHR, thereby inhibiting fusion between viral and target cell membranes. Here we present data to demonstrate that, contrary to this belief, T-20 cannot form stable 6-HB with N-peptides derived from the NHR region, nor can it inhibit the 6-HB formation of the fusogenic core. Instead, it may interact with N-peptides to form unstable or insoluble complexes. Our data suggest that T-20 has a different mechanism of action from C34. The interaction of T-20 with viral NHR region alone may not prevent the formation of the fusion active gp41 core. We also demonstrate that the T-20-mediated anti-HIV activity can be significantly abrogated by peptides derived from the membrane-spanning domain in gp41 and coreceptor binding site in gp120. These new findings imply that T-20 inhibits HIV-1 entry by targeting multiple sites in gp41 and gp120. Further elucidation of the mechanism of action of T-20 will provide new target(s) for development of novel HIV entry inhibitors.
[Cord blood transplantation for adults]. (2002)

Current reports from Europe and USA show that unrelated cord blood transplantation (CBT) gives good results in treating with children with malignancies and other disorders. However, there are not enough patients in the adults to perform a comparison with other stem cell transplantations. In unrelated CBT, HLA disparity is not a limiting factor and the incidence and the severity of acute and chronic GVHD is lower, even in the state of HLA 2 or 3 antigen-mismatched transplant, than in other stem cell transplantation, but the number of cells infused is important. At this stage, unrelated CBT is an optional source of stem cells in adults patients with malignancies who lack HLA compatible donors in bone marrow donor registries. However, the choice of cord blood units containing large number of cells and good disease status at transplantation might improve results.
Human Ciliary Muscle Cell Responses to FP-Class Prostaglandin Analogs: Phosphoinositide Hydrolysis, Intracellular Ca 2+ Mobilization and MAP Kinase Activation (2003)

Phospholipase C induced phosphoinositide (PI) turnover, intracellular Ca(2+) ([Ca(2+)](i)) mobilization and mitogen-activated protein (MAP) kinase activation by FP-class prostaglandin analogs was studied in normal human ciliary muscle (h-CM) cells. Agonist potencies obtained in the PI turnover assays were: travoprost acid ((+)-fluprostenol; EC(50) = 2.6 +/- 0.8 nM) > bimatoprost acid (EC(50) = 3.6 +/- 1.2 nM) > (+/-)-fluprostenol (EC(50) = 4.3 +/- 1.3 nM) >> prostaglandin F(2 alpha) (PGF(2 alpha)) (EC(50) = 134 +/- 17 nM) > latanoprost acid (EC(50) = 198 +/- 83 nM) > S-1033 (EC(50) = 2930 +/- 1420 nM) > unoprostone (EC(50) = 5590 +/- 1490 nM) > bimatoprost (EC(50) = 9600 +/- 1100 nM). Agonist potencies in h-CM cells correlated well with those previously obtained for the cloned human ciliary body-derived FP receptor (r = 0.96, p< 0.001) and that present on h-TM cells (r = 0.94, p< 0.0001). Travoprost acid, PGF(2 alpha) and unoprostone also stimulated [Ca(2+)](i) mobilization in h-CM cells with travoprost acid being the most potent agonist. MAP kinase activity was stimulated in the h-CM cells with the following rank order of activity (at 100 nM): travoprost acid > PGF(2 alpha) > latanoprost acid > PGD(2) > bimatoprost > latanoprost = bimatoprost acid = fluprostenol > PGE(2) = S-1033 > unoprostone > PGI(2). The PI turnover, [Ca(2+)](i) mobilization and MAP kinase activation induced by several of these agonists was blocked by the FP receptor antagonist, AL-8810 (11 beta-fluoro-15-epiindanyl PGF(2 alpha)) (e.g. K(i) = 5.7 microM versus PI turnover). These studies have characterized the biochemical and pharmacological properties of the native FP prostaglandin receptor present on h-CM cells using three signal transduction mechanism assays and a broad panel of FP-class agonist analogs (including free acids of bimatoprost, travoprost and latanoprost) and the FP receptor antagonist, AL-8810.
Surface modification of polymeric biomaterials with poly(ethylene oxide), albumin, and heparin for reduced thrombogenicity (1993)

Appropriate surface modification has significantly improved the blood compatibility of polymeric biomaterials. This article reviews methods of surface modification with water-soluble polymers, such as polyethylene oxide (PEO), albumin, and heparin. PEO is a synthetic, neutral, water-soluble polymer, while albumin and heparin are a natural globular protein and an anionic polysaccharide, respectively. When grafted onto the surface, all three macromolecules share a common feature to reduce thrombogenicity of biomaterials. The reduced thrombogenicity is due to the unique hydrodynamic properties of the grafted macromolecules. In aqueous medium, surface-bound water-soluble polymers are expected to be highly flexible and extend into the bulk solution. Biomaterials grafted with either PEO, albumin, or heparin are able to resist plasma protein adsorption and platelet adhesion predominantly by a steric repulsion mechanism.
Intelligent Selection of Language Model Training Data (2010)

We address the problem of selecting nondomain-specific language model training data to build auxiliary language models for use in tasks such as machine translation. Our approach is based on comparing the cross-entropy, according to domainspecific and non-domain-specifc language models, for each sentence of the text source used to produce the latter language model. We show that this produces better language models, trained on less data, than both random data selection and two other previously proposed methods. 1
Differentiation of Gas Molecules Using Flexible and All-Carbon Nanotube Devices (2008)

Carbon nanotubes (CNTs) are extremely sensitive to the electronic perturbations from environmental gases. However, the electrical detection of carbon monoxide (CO) is still a challenge. Here we show that 1 ppm of CO can be electrically detected at room temperature using a CNT resistor and the detection is proposed related to the sidewall functionalities (COOH). A simple all-CNT electronic nose composed of two resistors (or one resistor plus one transistor) is able to differentiate CO and other oxidative gases (for example NO and NO2). The electronic nose is working on both conventional SiO2/Si and flexible substrates.
Idéal du mariage et plaisanterie (2006)

RésuméLa « dysharmonie » de la résidence (patrilocale) à la filiation (matrilinéaire) est attestée, ici ou là. Il ne s’agit nullement d’une erreur dans la description, mais bien d’une contradiction, laquelle ne peut qu’engendrer une dynamique historique dont il n’est nul besoin de chercher l’origine dans une causalité externe, accidentelle. Il arrive que les tensions générées par cette contradiction se donnent à voir dans le Jeu, saynètes amusantes de la vie quotidienne ou théâtralité du rite : des « relations à plaisanterie » comme on dit.
Gene therapy for severe combined immunodeficiency: are we there yet? (2007)

Inherited and acquired diseases of the hematopoietic system can be cured by allogeneic hematopoietic stem cell transplantation. This treatment strategy is highly successful when an HLA-matched sibling donor is available, but if not, few therapeutic options exist. Gene-modified, autologous bone marrow transplantation can circumvent the severe immunological complications that occur when a related HLA-mismatched donor is used and thus represents an attractive alternative. In this review, we summarize the advantages and limitations associated with the use of gene therapy to cure SCID. Insertional mutagenesis and technological improvements aimed at increasing the safety of this strategy are also discussed.
Methanol Oxidation at p-Si/Pt Electrodes. Evidence for Hot Hole Reactivity (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMethanol Oxidation at p-Si/Pt Electrodes. Evidence for Hot Hole ReactivityK. W. Frese Jr. and C. ChenCite this: J. Phys. Chem. 1995, 99, 16, 6074–6083Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://pubs.acs.org/doi/10.1021/j100016a050https://doi.org/10.1021/j100016a050research-articleACS PublicationsRequest reuse permissionsArticle Views116Altmetric-Citations1LEARN 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 options Get e-Alerts
Prevalence of High C-Reactive Protein in Persons with Serum Lipid Concentrations within Recommended Values (2004)

In 2000, approximately 12 million adults in the United States considered normolipidemic had high CRP concentrations. Additional studies to explore the role of CRP in cardiovascular disease risk assessment are needed.
Selection of Carbonic Anhydrase Variants Displayed on Phage (1997)

In all metalloenzymes, hydrophobic residues surround the metal binding site. In carbonic anhydrase II (CAII) residues Phe93, Phe95, and Trp97 flank two of the three histidines that coordinate zinc to form a hydrophobic cluster beneath the zinc binding site. A library of CAII variants differing in these hydrophobic amino acids was prepared using cassette mutagenesis, then displayed on filamentous phage, and screened for proteins retaining high zinc affinity. Wild-type CAII was enriched 20-fold by selection, and consensus residues at each position were identified from the enriched CAII variants (Ile, Phe, Leu, and Met at position 93; Ile, Leu, and Met at position 95; and Trp and Val at position 97). Highly selected variants have zinc affinity and catalytic activity nearly equal to that of wild-type CAII, indicating that the aromatic residues are not absolutely essential. However, the zinc dissociation rate constant and catalytic activity of the variants correlate with the volume of the amino acids at positions 93, 95, and 97. In summary, metalloenzyme variants displayed on phage can be selected on the basis of metal affinity; such methods will be useful for optimization of metal ion biosensors.
New frontiers in gene targeting and cloning: success, application and challenges in domestic animals and human embryonic stem cells (2003)

Until recently, precise modification of the animal genome by gene targeting was restricted to the mouse because germline competent embryonic stem cells are not available in any other mammalian species. Nuclear transfer (NT) technology now provides an alternative route for cell-based transgenesis in domestic species, offering new opportunities in genetic modification. Livestock that produce human therapeutic proteins in their milk, have organs suitable for xenotransplantation, or that could provide resistance to diseases such as spongiform encephalopathies have been produced by NT from engineered, cultured somatic cells. However, improvements in the efficiency of somatic cell gene targeting and a greater understanding of the reprogramming events that occur during NT are required for the routine application of what is currently an inefficient process. The ability to reprogramme and genetically manipulate cells will also be crucial for full exploitation of human embryonic stem (hES) cells, which offer unparalleled opportunities in human health and biotechnology. Particularly pertinent are directed differentiation of hES lines to specific cell lineages, production of cells that evade the patient's immune system and ensuring the safety of ensuing transplants. This review will discuss some of the successes, applications and challenges facing gene targeting in livestock and hES cells.
Human immunodeficiency virus infection of human bone marrow stromal fibroblasts (1990)

The human immunodeficiency virus (HIV) preferentially infects CD4 positive T cells and monocytes. Other human cell types have been reported to be infectable with HIV, including cells of mesenchymal origin. In this report, we show that both primary human bone marrow stromal fibroblasts and an immortalized human stromal fibroblast line are susceptible to HIV infection. These cells are capable of passing HIV to cells of lymphoid or myeloid lineage, and may thereby act as a reservoir of virus. This in vitro system may be a useful model for assessing the pathophysiology of hematopoietic dysfunction in AIDS patients.
Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: toward targeted treatments for immunosenescence (2013)

Immunosenescence is the functional deterioration of the immune system during natural aging. Despite increased susceptibility to bacterial infections in older adults, age-associated changes to neutrophil responses are only partially understood, and neutrophil migration has not been characterized in detail. Here we describe reduced chemotaxis but preserved chemokinesis toward a range of inflammatory stimuli in migrating neutrophils isolated from healthy older subjects. Cross-sectional data indicate that migratory behavior changes in the sixth decade of life. Crucially, aberrant migration may increase "bystander" tissue damage and heighten inflammation as a result of excess proteinase release during inaccurate chemotaxis, as well as reducing pathogen clearance. We show evidence of increased neutrophil proteinase activity in older adults, namely, raised levels of neutrophil proteinase substrate-derived peptides and evidence of primary granule release, associated with increased systemic inflammation. Inaccurate migration was causally associated with increased constitutive phosphoinositide 3-kinase (PI3K) signaling; untreated neutrophils from old donors demonstrated significant PI3K activation compared with cells from young donors. PI3K-blocking strategies, specifically inhibition of PI3Kγ or PI3Kδ, restored neutrophil migratory accuracy, whereas SHIP1 inhibition worsened migratory flaws. Targeting PI3K signaling may therefore offer a new strategy in improving neutrophil functions during infections and reduce inappropriate inflammation in older patients.