gebhart/patrepeval huggingface dataset:
Phosphatidylinositol 3-kinase activation is mediated by high-affinity interactions between distinct domains within the p110 and p85 subunits. (1994)

Domains of interaction between the p85 and p110 subunits of phosphatidylinositol 3-kinase (PI 3-kinase) were studied with the yeast two-hybrid expression system. A gene fusion between the GAL4 transactivation domain and p85 activated transcription from a GAL1-lacZ reporter gene when complemented with a gene fusion between the GAL4 DNA binding domain and p110. To define subdomains responsible for this interaction, a series of p85 deletion mutants were analyzed. A 192-amino-acid inter-SH2 (IS) fragment (residues 429 to 621) was the smallest determinant identified that specifically associated with p110. In analogous experiments, the subdomain within p110 responsible for interaction with p85 was localized to an EcoRI fragment encoding the amino-terminal 127 residues. Expression of these two subdomains [p85(IS) with p110RI] resulted in 100-fold greater reporter activity than that obtained with full-length p85 and p110. Although the p85(IS) domain conferred a strong interaction with the p110 catalytic subunit, this region was not sufficient to impart phosphotyrosine peptide stimulation of PI 3-kinase activity. In contrast, coexpression of the p110 subunit with full-length p85 or with constructs containing the IS sequences flanked by both SH2 domains of p85 [p85(n/cSH2)] or either of the individual SH2 domains [p85(nSH2+IS) or p85(IS+cSH2)] resulted in PI 3-kinase activity that was activated by a phosphotyrosine peptide. These data suggest that phosphotyrosine peptide binding to either SH2 domain generates an intramolecular signal propagated through the IS region to allosterically activate p110.
Functionalization of Porous Silicon Based Photonic Crystals with Organic Monolayers (2006)

Porous silicon photonic crystals were reacted with unsaturated molecules in thermal hydrosilylation reactions to form silicon-carbon linked monolayers with functional groups designed for biosensor preparation. The derivatization was followed by infrared, X-ray photoelectron and reflection spectroscopies. Monolayer formation on the internal surfaces of the porous silicon structures resulted in predictable changes of their optical properties. Long term stability studies showed that the monolayers did not prevent slow oxidation of the porous silicon matrix in air.
Immunomodulatory Properties of Maxadilan, the Vasodilator Peptide from Sand Fly Salivary Gland Extracts (1996)

Sand flies are the arthropod vector of leishmaniasis and salivary gland extracts from these flies exacerbate leishmaniasis in vivo. The mechanism of exacerbation appears to be due to immunomodulatory effects of the saliva on host immune function but the active component is unknown. The following studies reveal that maxadilan, the vasodilatory peptide present in sand fly salivary gland extracts, has immunomodulatory properties. To examine the effect of maxadilan on T cell proliferation, the peptide was added to murine spleen cells stimulated with either concanavalin A or plate-bound anti-T cell receptor antibody. Inhibition of proliferation was noted in a dose-dependent manner for both sets of experiments (P < 0.05). To examine the effect of maxadilan on alloantigen presentation, the peptide was added to mixed lymphocyte and mixed epidermal cell lymphocyte reactions. Inhibition of proliferation was found in these culture systems. Maxadilan also inhibited the delayed-type hypersensitivity reaction in mice (P < 0.05). These observations suggest a role for maxadilan in the pathogenesis of leishmaniasis since the peptide may inhibit the immune response at the site of parasite inoculation, allowing the infection to proceed.
Identification and Characterization of Pancreatic Eukaryotic Initiation Factor 2 α-Subunit Kinase, PEK, Involved in Translational Control (1998)

In response to various environmental stresses, eukaryotic cells down-regulate protein synthesis by phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2alpha). In mammals, the phosphorylation was shown to be carried out by eIF-2alpha kinases PKR and HRI. We report the identification and characterization of a cDNA from rat pancreatic islet cells that encodes a new related kinase, which we term pancreatic eIF-2alpha kinase, or PEK. In addition to a catalytic domain with sequence and structural features conserved among eIF-2alpha kinases, PEK contains a distinctive amino-terminal region 550 residues in length. Using recombinant PEK produced in Escherichia coli or Sf-9 insect cells, we demonstrate that PEK is autophosphorylated on both serine and threonine residues and that the recombinant enzyme can specifically phosphorylate eIF-2alpha on serine-51. Northern blot analyses indicate that PEK mRNA is expressed in all tissues examined, with highest levels in pancreas cells. Consistent with our mRNA assays, PEK activity was predominantly detected in pancreas and pancreatic islet cells. The regulatory role of PEK in protein synthesis was demonstrated both in vitro and in vivo. The addition of recombinant PEK to reticulocyte lysates caused a dose-dependent inhibition of translation. In the Saccharomyces model system, PEK functionally substituted for the endogenous yeast eIF-2alpha kinase, GCN2, by a process requiring the serine-51 phosphorylation site in eIF-2alpha. We also identified PEK homologs from both Caenorhabditis elegans and the puffer fish Fugu rubripes, suggesting that this eIF-2alpha kinase plays an important role in translational control from nematodes to mammals.
Molecular tectonics: modulation of size and shape of cuboid 3-D coordination networks (2008)

The pore size and shape of cuboid 3-D coordination networks may be modulated by combining rigid neutral organic tectons of different length bearing two pyridines oriented in a divergent fashion with zinc dication and SiF6 dianion behaving as a metallic node and as an inorganic tecton, respectively.
Impact of Hydrolysis at High Temperatures on the Apparent Viscosity of Carboxybetaine Viscoelastic Surfactant-Based Acid: Experimental and Molecular Dynamics Simulation Studies (2012)

Summary Carboxybetaine viscoelastic surfactants have been applied in acid diversion and fracturing treatments in which high temperatures and low pH are usually involved. These surfactants are subjected to hydrolysis under such conditions because of the existence of a peptide group (-CO-NH-) in their molecules, leading to changes in the rheological properties of the acid. The objective of this paper is to study the impact of hydrolysis at high temperatures on the apparent viscosity of carboxybetaine viscoelastic surfactant-based acids, and propose the mechanism of viscosity changes by molecular dynamics (MD) simulations. Surfactant-acid solutions with different compositions (surfactant concentration varied from 4 to 8 wt%) were incubated at 190°F for 1 to 6 hours. Solutions were then partially spent by CaCO3 until the sample pH was 4.5, and the apparent viscosity was measured using a high-temperature/high-pressure (HT/HP) viscometer. To understand the mechanism for viscosity changes on the molecular level, MD simulations were carried out on spent surfactant-acid aqueous systems using the Materials Studio 5.0 Package. It was found that short-time hydrolysis at high temperatures (for example, 1 to 2 hours at 190°F) led to a significant increase in surfactant-acid viscosity. However, after incubation for 3 hours, phase separation occurred and the acid lost its viscosity. Simulation results showed that viscosity changes of amido-carboxybetaine surfactant acid by hydrolysis at high temperatures may be caused by different micellar structures formed by carboxybetaine and fatty acid soap, its hydrolysis product. The optimum molar ratio of amido-carboxybetaine and fatty acid soap to form wormlike micelles was found to be nearly 3:1 from our simulations. Our results indicate that hydrolysis at high temperatures has a great impact on surfactant-acid rheological properties. Short time viscosity build-up and effective gel breakdown can be achieved if surfactant-acid treatments are carefully designed; otherwise, unexpected viscosity reduction and phase separation may occur, which will affect the outcome of acid treatments.
Synthesis of Diastereomerically Pure Nucleotide Phosphoramidates (2011)

Prodrugs of therapeutic nucleoside monophosphates masked as phosphoramidate derivatives have become an increasingly important class of antiviral drugs in pharmaceutical research for delivering nucleotides in vitro and in vivo. Conventionally, phosphoramidate derivatives are prepared as a mixture of two diastereomers. We report a class of stable phosphoramidating reagents containing an amino acid ester and two phenolic groups, one unsubstituted and the other with electron-withdrawing substituents. The reagents can be isolated as single diastereomers and reacted with the 5'-hydroxyl group of nucleosides through selective nucleophilic displacement of the substituted phenol to prepare single diastereomer phosphoramidate products. This method has been used to prepare the HCV clinical candidate PSI-7977 in high yield and high diastereomeric purity.
Quantitation of Effect of Several Stimuli on the Approach of Aedes aegypti1 (1966)

Journal Article Quantitation of Effect of Several Stimuli on the Approach of Aedes aegypti Get access A. A. Khan, A. A. Khan Division of Dermatology, Department of Medicine, University of California School of Medicine, San Francisco Search for other works by this author on: Oxford Academic PubMed Google Scholar H. Maibach, I., H. Maibach, I. Division of Dermatology, Department of Medicine, University of California School of Medicine, San Francisco Search for other works by this author on: Oxford Academic PubMed Google Scholar W. G. Strauss, W. G. Strauss Division of Dermatology, Department of Medicine, University of California School of Medicine, San Francisco Search for other works by this author on: Oxford Academic PubMed Google Scholar W. R. Fenley W. R. Fenley Division of Dermatology, Department of Medicine, University of California School of Medicine, San Francisco Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Economic Entomology, Volume 59, Issue 3, 1 June 1966, Pages 690–694, https://doi.org/10.1093/jee/59.3.690 Published: 01 June 1966 Article history Accepted: 09 February 1966 Published: 01 June 1966
Restoration of Wild-type Pathogenicity to an Attenuated DNA Polymerase Mutant of Herpes Simplex Virus Type 1 (1986)

The drug-resistant variant, RSC-26, which was derived from the herpes simplex virus type 1 wild-type strain SC16, expresses an altered DNA polymerase and has reduced pathogenicity in animal models. To determine whether the attenuation in pathogenicity was due solely to mutation in the polymerase gene, a fragment of the wild-type gene was cloned, transferred into the genome of RSC-26 and recombinants were isolated. Three recombinants examined had similar properties to wild-type virus with respect to their sensitivity to antiviral drugs, DNA polymerase activities and their pathogenicity for mice. These results strongly suggest that expression of the altered polymerase of RSC-26 results in attenuated pathogenicity.
Oral Polio Vaccination during Pregnancy: No Increase in the Occurrence of Congenital Malformations (1993)

To examine the possible association between maternal vaccination with oral polio-virus and congenital malformations of the child, use was made of a nationwide mass vaccination in Finland. During a restricted period in 1985, a vaccination with trivalent oral poliovirus was implemented with coverage of 94% of the population. The study population was chosen from three major hospitals in the Greater Helsinki Region in Finland which deliver over 95% of the children of their catchment area. One study and two reference cohorts were delineated; the former consisted of pregnancies that were in their first trimester during the vaccination period. The two reference cohorts included mothers from the same hospitals whose pregnancies were likewise in the first trimester during the corresponding time period in 1984 and 1986, i.e., 12 months before and after the study period. Each cohort consisted of approximately 3,000 mothers/children whose delivery and hospital records were manually perused by trained nurses. All the structural malformations reflecting an impaired organogenesis during the sensitive first trimester were monitored. A total of 209 (2.3%) such malformations were recorded and characterized. There were no differences between the study and reference cohorts (risk ratio = 0.7, 95% confidence interval 0.5-1.0). According to the authors' power estimate, an additional prevalence greater than 0.5% would have been detected. The authors conclude that administration of oral poliovirus vaccine during early pregnancy was not associated with an elevated risk of congenital malformations.
Cellulosic hydrolysate toxicity and tolerance mechanisms in Escherichia coli (2009)

The sustainable production of biofuels will require the efficient utilization of lignocellulosic biomass. A key barrier involves the creation of growth-inhibitory compounds by chemical pretreatment steps, which ultimately reduce the efficiency of fermentative microbial biocatalysts. The primary toxins include organic acids, furan derivatives, and phenolic compounds. Weak acids enter the cell and dissociate, resulting in a drop in intracellular pH as well as various anion-specific effects on metabolism. Furan derivatives, dehydration products of hexose and pentose sugars, have been shown to hinder fermentative enzyme function. Phenolic compounds, formed from lignin, can disrupt membranes and are hypothesized to interfere with the function of intracellular hydrophobic targets. This review covers mechanisms of toxicity and tolerance for these compounds with a specific focus on the important industrial organism Escherichia coli. Recent efforts to engineer E. coli for improved tolerance to these toxins are also discussed.
Further studies on glucametacin in rheumatoid arthritis and in other chronic types of rheumatism (1981)

Twenty-three patients with rheumatoid arthritis and 9 patients with other forms of rheumatic diseases were treated for 20 days with 420 mg glucametacin per day, given as three 140 mg capsules. The treatment produced anti-inflammatory effects which were rated as good in about half the cases, with improvement of the majority of the clinical parameters studied. There were mild digestive side-effects. One patient with gallstones developed biliary colic, but the relationship of this to glucametacin treatment was not clear. The results obtained in the 32 patients treated with 140 mg glucametacin capsules were very similar to those which the same authors had observed in a very extensive case series of patients with rheumatic diseases treated with the same daily dose, but given as 70 mg capsules. It is suggested that the new preparation, which halves the number of capsules taken each day, is to be preferred to the smaller dose capsules.
Direct Covalent Grafting of Conjugated Molecules onto Si, GaAs, and Pd Surfaces from Aryldiazonium Salts (2003)

Using aryldiazonium salts that are air-stable and easily synthesized, we describe here a one-step, room-temperature route to direct covalent bonds between π-conjugated organic molecules on three material surfaces: Si, GaAs, and Pd. The Si can be in the form of single crystal Si including heavily doped p-type Si, intrinsic Si, heavily doped n-type Si, on Si(111) and Si(100), and on n-type polycrystalline Si. The formation of the aryl−metal or aryl−semiconductor bond attachments was confirmed by corroborating evidence from ellipsometry, reflectance FTIR, XPS, cyclic voltammetry, and AFM analyses of the surface-grafted monolayers. A data-encompassing explanation for the mechanism suggests a diazonium activation by reduction at the open circuit potential, with aryl radical secondary products bonding to the surface. The synthetic details are included for preparing the surface-grafted monolayers and the precursor diazonium salts. This spontaneous diazonium activation reaction offers an attractive route to highly passivating, robust monolayers and multilayers on many surfaces that allow for strong bonds between carbon and surface atoms with molecular species that are near perpendicular to the surface.
Protecting data from malicious software (2003)

Corruption or disclosure of sensitive user documents can be among the most lasting and costly effects of malicious software attacks. Many malicious programs specifically target files that are likely to contain important user data. Researchers have approached this problem by developing techniques for restricting access to resources on an application-by-application basis. These so-called "sandbox environments," though effective, are cumbersome and difficult to use. In this paper, we present a prototype Windows NT/2000 tool that addresses malicious software threats to user data by extending the existing set of file-access permissions. Management and configuration options make the tool unobtrusive and easy to use. We have conducted preliminary experiments to assess the usability of the tool and to evaluate the effects of improvements we have made. Our work has produced an intuitive data-centric method of protecting valuable documents that provides an additional layer of defense beyond existing antivirus solutions.
Microdomains in block copolymers and multiplets in ionomers: parallels in behavior (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTMicrodomains in block copolymers and multiplets in ionomers: parallels in behaviorIrina A. Nyrkova, Alexei R. Khokhlov, and Masao DoiCite this: Macromolecules 1993, 26, 14, 3601–3610Publication Date (Print):July 1, 1993Publication History Published online1 May 2002Published inissue 1 July 1993https://pubs.acs.org/doi/10.1021/ma00066a019https://doi.org/10.1021/ma00066a019research-articleACS PublicationsRequest reuse permissionsArticle Views476Altmetric-Citations146LEARN 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 Get e-Alerts
A novel in vitro survival assay of small intestinal stem cells after exposure to ionizing radiation (2014)

The microcolony assay developed by Withers and Elkind has been a gold standard to assess the surviving fraction of small intestinal stem cells after exposure to high (≥8 Gy) doses of ionizing radiation (IR), but is not applicable in cases of exposure to lower doses. Here, we developed a novel in vitro assay that enables assessment of the surviving fraction of small intestinal stem cells after exposure to lower IR doses. The assay includes in vitro culture of small intestinal stem cells, which allows the stem cells to develop into epithelial organoids containing all four differentiated cell types of the small intestine. We used Lgr5-EGFP-IRES-CreERT2/ROSA26-tdTomato mice to identify Lgr5(+) stem cells and their progeny. Enzymatically dissociated single crypt cells from the duodenum and jejunum of mice were irradiated with 7.25, 29, 101, 304, 1000, 2000 and 4000 mGy of X-rays immediately after plating, and the number of organoids was counted on Day 12. Organoid-forming efficiency of irradiated cells relative to that of unirradiated controls was defined as the surviving fraction of stem cells. We observed a significant decrease in the surviving fraction of stem cells at ≥1000 mGy. Moreover, fluorescence-activated cell sorting analyses and passage of the organoids revealed that proliferation of stem cells surviving IR is significantly potentiated. Together, the present study demonstrates that the in vitro assay is useful for quantitatively assessing the surviving fraction of small intestinal stem cells after exposure to lower doses of IR as compared with previous examinations using the microcolony assay.
Purification and characterization of the branched chain alpha-ketoacid dehydrogenase complex from Saccharomyces cerevisiae. (1993)

Branched chain alpha-ketoacid dehydrogenase complex was purified from Saccharomyces cerevisiae by polyethylene glycol fractionation and chromatography on Sephacryl S-200, DEAE-cellulose and Sepharose CL-2B. Electrophoresis on sodium dodecyl sulfate-polyacrylamide gels indicated the enzyme contained subunits of M(r) = 57,000, 52,000, 47,000 and 38,000. The specific activity of the purified enzyme was 0.82 mumol NADH/min/mg protein at 30 degrees C with 16 mM alpha-ketoisovalerate as substrate. The apparent Km values for alpha-ketoisovalerate, alpha-ketoisocaproate and alpha-keto-beta-methylvalerate were 21, 22, and 20 mM, respectively. The preparation was also able to oxidize the intermediates of threonine and methionine metabolism, alpha-keto-gamma-methiolbutyrate and alpha-ketobutyrate, with Km values of 13 and 8 mM, respectively.
Optimum design for multiple-phase-shift distributed feedback laser (1988)

An optimum design for the multiple-phase-shift distributed feedback (MPS-DFB) laser with three phase shifts in the corrugation was established theoretically. It was shown that the optimised MPS-DFB laser gives sufficient threshold gain difference and uniform field distribution even for strong coupling. Therefore, the long cavity MPS-DFB laser is expected to give stable single-longitudinal-mode operation at high injection levels and give a minimum linewidth of less than 500 kHz.
Multiple Roles of the PI3K/PKB (Akt) Pathway in Cell Cycle Progression (2003)

As its role in tumor progression emerges, the PI3K/PKB (Akt) pathway presents an appealing cancer therapeutic target. Recent studies have investigated the mechanisms underlying the tumor-promoting effects of this pathway. PKB triggers a network that positively regulates G1/S cell cycle progression through inactivation of GSK3-beta, leading to increased cyclin D1, and inhibition of Forkhead family transcription factors and the tumor suppressor tuberin (TSC2), leading to reduction of p27Kip1. The identification of p21Waf1/Cip1 and p27Kip1 as novel substrates of PKB provided new insights into mechanisms whereby hyperactivation of this lipid signaling pathway may lead to cell cycle deregulation in human cancers. The PI3K pathway may also play a key role in the G2/M transition and its constitutive activation may lead to defects in DNA damage checkpoint control.