gebhart/patrepeval huggingface dataset:
The insulinomimetic agents H2O2 and vanadate stimulate protein tyrosine phosphorylation in intact cells. (1990)

H2O2 and vanadate are known insulinomimetic agents. Together they induce insulin's bioeffects with a potency which exceeds that seen with insulin, vanadate, or H2O2 alone. Employing Western blotting with anti-P-Tyr antibodies, we have identified in Fao cells at least four proteins (pp180, 150, 114, and 100) whose P-Tyr content is rapidly increased upon treatment of the cells with 3 mM H2O2. Tyrosine phosphorylation of these and additional proteins was markedly potentiated (6-10-fold) when 100 microM sodium orthovanadate was added together with H2O2. The effects of H2O2 and vanadate on protein tyrosine phosphorylation were rapid and specific. The enhanced tyrosine phosphorylation was accompanied by a concomitant inhibition of a cytosolic protein tyrosine phosphatase activity. The latter was inhibited by 50% in 3 mM H2O2-treated cells. The inhibitory effect was augmented in the combined presence of H2O2 and vanadate. Half- and maximal effects of vanadate were obtained at 15 microM and 1 mM, respectively. Vanadate (1 mM) alone, added to the cells, had only a trivial effect on protein tyrosine phosphatase activity. A 45-s challenge with insulin (10(-7) M) of cells pretreated with H2O2 largely mimicked the potentiating effects of vanadate on protein tyrosine phosphorylation but not on protein tyrosine phosphatase activity. Our results suggest the involvement of multiple tyrosine-phosphorylation proteins in mediating the biological effects of H2O2/vanadate. Their enhanced phosphorylation can be attributed at least in part, to the inhibitory effects exerted by H2O2 alone, or in combination with vanadate, on protein tyrosine phosphatase activity. The similarity between proteins phosphorylated in Fao cells in response to H2O2/vanadate or H2O2/insulin, suggests that either treatment stimulates protein tyrosine kinases having similar substrate specificities. The insulin receptor kinase is a likely candidate as its activity is markedly enhanced either by insulin (plus H2O2) or by H2O2/vanadate.
Extensive loss of heterozygosity accounts for differential mutation rate on chromosome 17q in human lymphoblasts (1995)

In order to investigate the influence of loss of heterozygosity (LOH) events on mutation rate, we studied two closely related human lymphoblastoid cell lines, AHH-1 (h2E1.v2) and MCL-5, which are heterozygous at the tk locus (chromosome 17q23-25). Although they have similar mutant fractions at the hprt locus, the mutant fraction and rate at tk is four to five times higher in AHH-1. Analysis of 58 spontaneous TK- mutants from AHH-1 and MCL-5 showed that the occurrence of LOH events was more frequent (23/24) in AHH-1 than MCL-5 (16/34). A set of five microsatellite polymorphism loci was used to map the extent of LOH along chromosome 17q. In AHH-1 cells, 15/23 of the LOH events encompassed at least 35% of the sex-averaged genetic length of chromosome 17q (98 cM). Additionally, the next most extensive category of LOH accounted for 5/23 TK- mutants, and encompassed at least 17 cM. In contrast, LOH events observed in MCL-5 are very restricted in extent; only one LOH tract extended as far as 4 cM from tk. The higher mutation rate at tk in AHH-1 can, therefore, be entirely attributed to the recovery of chromosomal scale LOH in viable, normal growth TK- mutants. Furthermore, these data demonstrate that the regional potential for LOH is likely to be an important determinant of mutation rate for loci within that chromosomal segment.
Neisseria meningitidis bacteremia in association with deficiency of the sixth component of complement (1979)

The serum of a 26-year-old black man with a recent episode of meningococcemia complicated by meningitis and arthritis was found to lack hemolytic complement activity. The sixth component of complement was not detected by functional or immunochemical assays whereas other components were normal by hemolytic assay. His fresh acute-phase serum lacked complement-mediated bactericidal activity against the homologous strain of Neisseria meningitidis, but the addition of fresh normal serum or purified C6 restored bactericidal activity as well as hemolytic activity. The absence of C6 activity could not be accounted for on the basis of an inhibitor. Opsonization and chemotaxis functioned normally. Histocompatibility typing of family members did not demonstrate evidence for genetic linkage of C6 deficiency with the major histocompatibility loci. This report represents the first published case of C6 deficiency associated with bacteremic Neisseria infections in which antimeningococcal bactericidal antibodies have been definitively demonstrated against the homologous strain in the acute phase of the illness.
Epigenetic Regulation of Cellular Memory by the Polycomb and Trithorax Group Proteins (2004)

During the development of multicellular organisms, cells become different from one another by changing their genetic program in response to transient stimuli. Long after the stimulus is gone, "cellular memory" mechanisms enable cells to remember their chosen fate over many cell divisions. The Polycomb and Trithorax groups of proteins, respectively, work to maintain repressed or active transcription states of developmentally important genes through many rounds of cell division. Here we review current ideas on the protein and DNA components of this transcriptional memory system and how they interact dynamically with each other to orchestrate cellular memory for several hundred genes.
Synthesis of silsesquioxanes having photochromic dithienylethene pendant groups (1999)

Silsesquioxanes having 1-(2-methoxy-1-benzothiophen-3-yl)-2-[5-(4-butylphenyl)-2, 4-dimethylthiophen-3-yl]perfluorocyclopentenes as the pendant groups were synthesized. Photochemical conversion from the open-ring to the closed-ring forms of the dithienylethenes increases when the methyl group at 2-position of the benzothiophene ring is replaced by a methoxy group. The conversion is dependent on the content of dithienylethene in the polymer chain. No appreciable difference in the photochemical conversion was observed below and above the glass transition temperature (Tg) of the polymer films. The activation energies of coloration and bleach processes were obtained to be 0–1 and 1–3 kcal/mol, respectively.
The Generation and Selection of the T Cell Repertoire: Insights from Studies of the Molecular Basis of T Cell Recognition (1988)

The molecular basis of T cell corecognition of antigen and products of the major histocompatibility complex (MHC) was examined using the technique of DNA-mediated gene transfer. Introduction of the genes encoding the alpha and beta chains of the clonotypic molecule (Ti) of the pigeon cytochrome c-specific, I-Ek-restricted murine T cell hybridoma 2B4 into the human leukemic T cell Jurkat or its T3- variants led to the surface expression of various dimeric combinations of human and mouse Ti chains. All alpha beta dimers were associated in a 1:1 ratio with the chains of the T3 complex and all Ti-T3 complexes could transmit effective transmembrane signals for IL2 gene activation following binding and cross-linking by anti-T3 or anti-clonotypic antibodies. However, only the reconstituted mouse 2B4 alpha beta dimer mediated functional responses to antigen-presenting cells bearing the appropriate combination of antigen and Ia molecules. The fine specificity of the antigen-MHC molecule responses precisely matched that of the 2B4 T cell gene donor, establishing that the alpha beta clonotypic molecule is both necessary and sufficient to fully define the dual specificity of a T cell. This result, together with similar data from other laboratories, provides direct evidence in favor of the "single receptor" model of T cell recognition. Analysis of past experiments looking for independent recognition of antigen vs. MHC molecules led us to conclude that limitations on either formation of mixed receptor dimers or of appropriate antigen peptide-Ia molecule pairs may have limited the utility of these studies in providing an answer to this question. Therefore, additional gene transfer experiments were carried out to investigate the role of the two chains of the alpha beta heterodimer in controlling antigen vs. MHC molecule specificity. Our results showed that under conditions in which it was assured that antigen-Ia complexes formed, one could produce a receptor molecule composed of the alpha chain of one T cell hybridoma (2H10) and the beta chain of a second hybridoma (2B4) with a mixed antigen and MHC molecule specificity that could be predicted based on the specificities of the parent T cells. We discuss at length the implication of this result for the issue of single- vs. dual-site recognition models of T cell receptor function. In addition to these results looking directly at specificity of receptor molecules, we have also analyzed expression of various combinations of Ti chains. For alpha and beta, clear asymmetries in the efficiency of surface receptor expression were observed for certain pairs of chains.(ABSTRACT TRUNCATED AT 400 WORDS)
Slowing Down after a Mild Traumatic Brain Injury: A Strategy to Improve Cognitive Task Performance? (2011)

Long-term persistent attention and memory difficulties following a mild traumatic brain injury (TBI) often go undetected on standard neuropsychological tests, despite complaints by mild TBI individuals. We conducted a visual Repetition Detection working memory task to digits, in which we manipulated task difficulty by increasing cognitive load, to identify subtle deficits long after a mild TBI. Twenty-six undergraduate students with a self-report of one mild TBI, which occurred at least 6 months prior, and 31 non-head-injured controls took part in the study. Participants were not informed until study completion that the study's purpose was to examine cognitive changes following a mild TBI, to reduce the influence of "diagnosis threat" on performance. Neuropsychological tasks did not differentiate the groups, though mild TBI participants reported higher state anxiety levels. On our working memory task, the mild TBI group took significantly longer to accurately detect repeated targets on our task, suggesting that slowed information processing is a long-term consequence of mild TBI. Accuracy was comparable in the low-load condition and, unexpectedly, mild TBI performance surpassed that of controls in the high-load condition. Temporal analysis of target identification suggested a strategy difference between groups: mild TBI participants made a significantly greater number of accurate responses following the target's offset, and significantly fewer erroneous distracter responses prior to target onset, compared with controls. Results suggest that long after a mild TBI, high-functioning young adults invoke a strategy of delaying their identification of targets in order to maintain, and facilitate, accuracy on cognitively demanding tasks.
In situ epitaxial growth of ordered FePt (001) films with ultra small and uniform grain size using a RuAl underlayer (2005)

In situ epitaxial growth of ordered FePt thin films with small and uniform grain size using RuAl underlayer is reported. A transmission electron microscopy image of a 20-nm RuAl layer deposited on a glass substrate revealed small (D∼5.0nm) and uniform (ΔD∕D∼15%) grains. The (001) texture was formed in RuAl films at a substrate temperature higher than 100 °C. The FePt L10 (001) texture with mean grain size of 6.63 nm and narrow size distribution (17%) has been successfully induced using a RuAl underlayer at a substrate temperature of 400 °C. The influences of the RuAl composition ratio and Pt interlayer were studied.
Release mechanisms for polyelectrolyte capsules (2006)

Polyelectrolyte capsules have recently been introduced as new microscopic vehicles which could have high potential in the biomedical field. In this critical review we give an introduction to the layer-by-layer (LbL) technique which is used to fabricate these polyelectrolyte capsules as well as to the different triggers that have been exploited to obtain drug release from these capsules. Furthermore, other types of triggered delivery systems are compared and critically discussed with regard to their clinical relevance. (171 references.).
Assay of interferon and viral antibodies in the cerebrospinal fluid in clinical neurology and psychiatry. (1979)

Cerebrospinal fluids (CSF) of 245 neurological and 194 psychiatric patients were tested for viral antibodies and interferon. Complement dependent neutralizing antibodies to Herpesvirus hominis 1 were found in the CSF of patients with encephalitis (50.6%), meningitis (35.4%), lesions of peripheral nerves (36.9%), sclerosis multiplex (41.2%), schizophrenia (31.9%), senile dementia (51.4%), mental retardation (11.1%), ethylism (43.5%). Neutralizing antibodies to tick-borne encephalitis virus were found in the CSF of 38% patients with encephalitis, in 14% meningitis, 11% lesions of peripheral nerves and also in 5.6--11.8% of psychiatric patients. In encephalitis, meningitis and in lesions of peripheral nerves were found in the CSF frequently plaque neutralizing antobidies to the tick-borne orbivirus Lipovník, complement-fixing antibodies to lymphocytic choriomeningitis virus and hemagglutination inhibiting antibodies to measles virus. In multiple sclerosis were detected CSF antibodies to measles virus (44%), Herpesvirus hominis 1 (41.2%) and Lipovník virus (52.6%). In neurological patients were observed CSF antibodies simultaneously to two or three viruses in 16.7 to 40.6%, while in psychiatric patients in zero to 4.6%. CSF interferon was found in psychiatric patients with an equal or even higher incidence (33.7 to 57.1%) than in the neurological patients (29.6--38.6%, in multiple sclerosis only 16.7%). Non-interferon virus inhibitors were excluded. The evaluation of the ratio of serum and CSF titers of viral antibodies and of interferon indicated local synthesis of both in the central nervous system -- with the exception of antibodies to Herpesvirus hominis 1 in CSF of some patients with very high titres in serum and probable lesions of the blood brain barrier.
In acute myeloid leukemia, B7-H1 (PD-L1) protection of blasts from cytotoxic T cells is induced by TLR ligands and interferon-gamma and can be reversed using MEK inhibitors (2010)

B7-H1 (PD-L1) is a B7-related protein that inhibits T-cell responses. B7-H1 participates in the immunoescape of cancer cells and is also involved in the long-term persistence of leukemic cells in a mouse model of leukemia. B7-H1 can be constitutively expressed by cancer cells, but is also induced by various stimuli. Therefore, we examined the constitutive and inducible expression of B7-H1 and the consequences of this expression in human acute myeloid leukemia (AML). We analyzed B7-H1 expression in a cohort of 79 patients with AML. In addition, we studied blast cells after incubation with interferon-gamma or toll-like receptors (TLR) ligands. Finally, we evaluated functionality of cytotoxic T-cell activity against blast cells. Expression of B7-H1 upon diagnosis was high in 18% of patients. Expression of TLR2, 4 and 9 was detected in one-third of AML samples. Expression of TLR2 and TLR4 ligands or IFN-γ induced by B7-H1 was found to protect AML cells from CTL-mediated lysis. Spontaneous B7-H1 expression was also found to be enhanced upon relapse in some patients. MEK inhibitors, including UO126 and AZD6244, reduced B7-H1 expression and restored CTL-mediated lysis of blast cells. In AML, B7-H1 expression by blasts represents a possible immune escape mechanism. The inducibility of B7-H1 expression by IFN-γ or TLR ligands suggests that various stimuli, either produced during the immune response against leukemia cells or released by infectious microorganisms, could protect leukemic cells from T cells. The efficacy of MEK inhibitors against B7-H1-mediated inhibition of CTLs suggests a possible cancer immunotherapy strategy using targeted drugs.
Tobacco etch virus protease: mechanism of autolysis and rational design of stable mutants with wild-type catalytic proficiency (2001)

Because of its stringent sequence specificity, the catalytic domain of the nuclear inclusion protease from tobacco etch virus (TEV) is a useful reagent for cleaving genetically engineered fusion proteins. However, a serious drawback of TEV protease is that it readily cleaves itself at a specific site to generate a truncated enzyme with greatly diminished activity. The rate of autoinactivation is proportional to the concentration of TEV protease, implying a bimolecular reaction mechanism. Yet, a catalytically active protease was unable to convert a catalytically inactive protease into the truncated form. Adding increasing concentrations of the catalytically inactive protease to a fixed amount of the wild-type enzyme accelerated its rate of autoinactivation. Taken together, these results suggest that autoinactivation of TEV protease may be an intramolecular reaction that is facilitated by an allosteric interaction between protease molecules. In an effort to create a more stable protease, we made amino acid substitutions in the P2 and P1' positions of the internal cleavage site and assessed their impact on the enzyme's stability and catalytic activity. One of the P1' mutants, S219V, was not only far more stable than the wild-type protease (approximately 100-fold), but also a more efficient catalyst.
.sigma.-Bond metathesis for carbon-hydrogen bonds of hydrocarbons and Sc-R (R = H, alkyl, aryl) bonds of permethylscandocene derivatives. Evidence for noninvolvement of the .pi. system in electrophilic activation of aromatic and vinylic C-H bonds (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT.sigma.-Bond metathesis for carbon-hydrogen bonds of hydrocarbons and Sc-R (R = H, alkyl, aryl) bonds of permethylscandocene derivatives. Evidence for noninvolvement of the .pi. system in electrophilic activation of aromatic and vinylic C-H bondsMark E. Thompson, Steven M. Baxter, A. Ray Bulls, Barbara J. Burger, Michael C. Nolan, Bernard D. Santarsiero, William P. Schaefer, and John E. BercawCite this: J. Am. Chem. Soc. 1987, 109, 1, 203–219Publication Date (Print):January 1, 1987Publication History Published online1 May 2002Published inissue 1 January 1987https://pubs.acs.org/doi/10.1021/ja00235a031https://doi.org/10.1021/ja00235a031research-articleACS PublicationsRequest reuse permissionsArticle Views4690Altmetric-Citations731LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
Functionalized polystyrene nanoparticles as a platform for studying bio–nano interactions (2014)

Nanoparticles of various shapes, sizes, and materials carrying different surface modifications have numerous technological and biomedical applications. Yet, the mechanisms by which nanoparticles interact with biological structures as well as their biological impact and hazards remain poorly investigated. Due to their large surface to volume ratio, nanoparticles usually exhibit properties that differ from those of bulk materials. Particularly, the surface chemistry of the nanoparticles is crucial for their durability and solubility in biological media as well as for their biocompatibility and biodistribution. Polystyrene does not degrade in the cellular environment and exhibits no short-term cytotoxicity. Because polystyrene nanoparticles can be easily synthesized in a wide range of sizes with distinct surface functionalizations, they are perfectly suited as model particles to study the effects of the particle surface characteristics on various biological parameters. Therefore, we have exploited polystyrene nanoparticles as a convenient platform to study bio-nano interactions. This review summarizes studies on positively and negatively charged polystyrene nanoparticles and compares them with clinically used superparamagnetic iron oxide nanoparticles.
Friedel—Crafts Acylation of Indoles in Acidic Imidazolium Chloroaluminate Ionic Liquid at Room Temperature. (2002)

Abstract For Abstract see ChemInform Abstract in Full Text.
Immigration and U.S. Foreign Policy (2017)

US immigration policy traditionally has been regarded as a domestic policy issue a perception apparent in the virtual absence of immigration policy concerns in US foreign policy debate. The lag in appreciating immigration policy as a component of foreign policy seems to be more a matter of convention of outdated issue identification. Underlying assumption concerning the fundamental nature of foreign policy and international politics have left migration matters outside the traditional focus of foreign policy analysis. The matter in which the enormous socioeconomic disparities between the advanced and the least developed countries affect international population flows is a subject that needs to be understood before immigration becomed a central concern of US foreign policy. No single model or classificatory scheme with which to analyze US immigration policy as foreign policy exists. One way to structure a consideration of US immigration policy as foreign policy would be to break down the general policy area to broad types of migrants concerned: immigrants illegal aliens temporary workers refugees and visitors. In each case the foreign policy significance of US policy seems somewhat different yet the categories are of mutual relevance to each other. The question is not whether foreign policy relevant change in US immigration policy comes but when and how it will come. 3 major scenarios seem possible. First immigration policy can stant as is and be slowly overwhelmed by the events and forces that already have prompted cries of alarm. The likely outcome would be a radical policy departure in the form of immigration restriction which would seek to seal off the US from international migration pressures. The foreign policy consequence of such a departure would be severe. A 2nd scenario could result from a continuing inability of the US to adapt to changing would circumstances as manifested in increasing global migratory and refungee pressures. Between the extremes of the 2 scenarious lies the 3rd option of a constructive response to the global immigration problem. The key to this response is creative and farsighted diplomacy.
Antimicrobial Drugs (2013)

Antibiotics play a vital role in dental practice for managing orofacial infections. They are used to manage existing infection and they are also used as prophylaxis for certain medical conditions and surgical procedures. This article will review pharmacological and therapeutic considerations for the proper use of these agents for dental infections.