gebhart/patrepeval huggingface dataset:
Mitigation of Radiation-Induced Damage by Targeting EGFR in Noncancerous Human Epithelial Cells (2013)

Methyl-2-cyano-3,12 dioxoolean-1,9 diene-28-oate (CDDO-Me) is an antioxidative, anti-inflammatory modulator, which activates the nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway. While CDDO-Me has radioprotective activity through Nrf2 activation in vitro and in vivo, its ability to mitigate radiation-induced damage when provided after irradiation has not been studied. Here we investigated whether CDDO-Me mitigates ionizing radiation (IR)-induced DNA damage in immortalized normal human colonic epithelial cells (HCECs) and bronchial epithelial cells (HBECs). DNA damage and clonogenic survival were assessed after treatment with CDDO-Me postirradiation. We observed that treatment with CDDO-Me within 30 min after irradiation improved both DNA damage repair and clonogenic survival independently of Nrf2. CDDO-Me activates the epidermal growth factor receptor (EGFR) related DNA repair responses. In the presence of CDDO-Me, EGFR is phosphorylated and translocates into the nucleus where it interacts with DNA-PKcs. CDDO-Me-mediated mitigation activity can be abrogated through depletion of EGFR, ectopic overexpression of mutant EGFR or inhibition of DNA-PKcs. While post-treatment of CDDO-Me protected noncancerous HCECs and HBECs against IR, cancer cells (HCT116 and MCF7) were not protected by CDDO-Me. These results suggest that targeting EGFR using CDDO-Me is a promising radiation mitigator with potential utility for first responders to nuclear accidents.
ANALYSIS OF ACCOMMODATIVE RESPONSE TIMES USING HISTOGRAM INFORMATION (1972)

An optometer is described that provides an electrical signal proportional to the amount of movement of the anterior surface of the crystalline lens. Dynamic recordings of this movement were made on a number of subjects tracking predictable (periodic) and nonpredictable target step movements. Histograms of the reaction times definitely show that the accommodation system can reduce its delay time when presented with a predictable stimulus. Typical accommodative reaction times are compared to those published by other authors in the literature. The change of anterior chamber depth, lens curvature, and pupil diameter are related to accommodative target distance by a photographic method and help to provide a clearer understanding of accommodative lens changes.
Human Monoclonal Antibodies Neutralizing Human Cytomegalovirus (1987)

Hybridomas producing human monoclonal antibodies (MAbs) against human cytomegalovirus (CMV) were generated by fusion of human spleen cells and mouse myeloma cells. Two of the six MAbs obtained neutralized viral infectivity even at concentrations lower than 1 microgram/ml. One MAb required complement for neutralization but the other did not. Both MAbs recognized viral proteins of Mr 130,000 and 55,000. Furthermore, these neutralizing MAbs bound to the surface membrane of CMV-infected cells. These results suggest that human MAbs may provide a new means of passive immunization against CMV infection in humans.
Copper-catalyzed cascade synthesis of benzimidazoquinazoline derivatives under mild condition (2011)

A convenient and efficient copper-catalyzed cascade method has been developed for the synthesis of benzimidazoquinazoline derivatives via reactions of readily available substituted 2-(2-halophenyl)benzoimidazoles with amidines or guanidine under mild conditions (even at room temperature).
Carrier mobilities and process stability of strained Si n- and p-MOSFETs on SiGe virtual substrates (2001)

Surface channel strained Si metal–oxide–semiconductor field-effect transistors (MOSFETs) are a leading contender for future high performance complementary metal–oxide–semiconductor (CMOS) applications. The carrier mobility enhancement of these devices is studied as a function of channel strain, and the saturation behavior for n- and p-channel devices is compared. Carrier mobility enhancements of up to 1.8 and 1.6 are achieved for n- and p-channel devices, respectively. The process stability of strained Si MOSFETs is also studied, and carrier mobility enhancement is shown to be robust after well implantation and virtual substrate planarization steps. The effects of high-temperature implant activation anneals are also studied. While no misfit dislocation introduction or strain relaxation is observed in these devices, increased interface state densities or alloy scattering due to Ge interdiffusion are shown to decrease mobility enhancements. Channel thickness effects are also examined for strained Si n-MOSFETs. Loss of carrier confinement severely limits the mobility of devices with the thinnest channels. Overall, surface channel strained Si MOSFETs are found to exhibit large carrier mobility enhancements over coprocessed bulk Si devices. This, combined with the high process stability exhibited by these devices, makes them superb candidates for future CMOS applications.
The immunosuppressive macrolides FK-506 and rapamycin act as reciprocal antagonists in murine T cells. (1990)

The structurally related immunosuppressive macrolides FK-506 and rapamycin (RAP) were previously shown to inhibit T cell stimulation through different mechanisms. FK-506 acts similarly to cyclosporin A (CsA) and prevents IL-2 production and IL-2R expression. RAP has little or no effect on these events but markedly impedes the response to IL-2. The present study was initiated to examine the possibility of a complementation between the immunosuppressive actions of RAP and FK-506 or CsA on various murine T cell responses. RAP potentiated the effect of CsA on proliferation and IL-2R expression in T cells stimulated with ionomycin + PMA. However, in the same system, RAP acted as a potent antagonist of FK-506 suppression. RAP also blocked FK-506- but not CsA-mediated inhibition of IL-2 mRNA induction. By using model systems sensitive to inhibition by RAP but not FK-506 we further demonstrated that FK-506 reciprocally behaves as an antagonist of RAP. In one such model, the stimulation of splenic T cells with IL-2 + PMA, FK-506, but not CsA, reversed the suppressive effect of RAP on proliferation. FK-506 also antagonized RAP-mediated inhibition with respect to the induction of Ly-6E Ag expression by IFN in YAC cells. To explore further the competition between the two macrolides at the cellular level, we performed binding experiments with a radiolabeled derivative of FK-506. Both FK-506 and RAP, but not CsA, inhibited the binding of this probe in YAC cells. Taken together, these data demonstrate that FK-506 and RAP antagonize each other's biologic activity and physically interact with a common receptor site(s) in T cells. Moreover, CsA acts at a site distinct from the cellular target(s) of FK-506 or RAP.
An Unexpected Major Groove Binding of Netropsin and Distamycin A to tRNAphe (1984)

Crystalline complexes of yeast tRNA(phe) and the oligopeptide antibiotics netropsin and distamycin A were prepared by diffusing drugs into crystals of tRNA. X-ray structure analyses of these complexes reveal a single common binding site for both drugs which is located in the major or deep groove of the tRNA T-stem. The netropsin-tRNA complex is stabilized by specific hydrogen bonds between the amide groups of the drug and the tRNA bases G51 O(6), U52 O(4) and G53 N(7) on one strand, and is further stabilized by electrostatic interactions between the positively charges guanidino side chain of the drug and the tRNA phosphate P53 on the same strand and the positively charged amidino propyl side chain and the phosphates P61, P62 and P63 on the opposite strand of the double helix. These results are in contrast to the implicated minor groove binding of these drugs to non-guanine sequences in DNA. The binding to the GUG sequence in tRNA implies that major groove binding to certain DNA sequences is possible.
Gain-of-function mutations in the tumor suppressor gene p53. (2000)

The tumor suppressor protein p53 is a multifunctional transcription factor involved in the control of cell cycle progression, DNA integrity, and cell survival. p53 is mutated in half of all tumors and has a wide spectrum of mutation types. p53 mutants show different degrees of dominance over coexpressed wild-type p53, and loss of the wild-type p53 allele has been observed frequently. Several p53 mutants can exert oncogenic functions beyond their negative domination over the wild-type p53 tumor suppressor functions. These so-called gain-of-function effects, such as enhancement of tumorigenicity and therapy resistance, were investigated in p53-null cells. The possible mechanisms by which p53 mutants exert their gain-of-function effects are reviewed. The existence of functional gains of certain p53 mutants has important ramifications for tumor prognosis and cancer therapies.
The Kaposi's Sarcoma–related Herpesvirus (KSHV)-encoded Chemokine vMIP-I is a Specific Agonist for the CC Chemokine Receptor (CCR)8 (1999)

The Kaposi's sarcoma-related herpesvirus (KSHV), also designated human herpesvirus 8, is the presumed etiologic agent of Kaposi's sarcoma and certain lymphomas. Although KSHV encodes several chemokine homologues (viral macrophage inflammatory protein [vMIP]-I, -II, and -III), only vMIP-II has been functionally characterized. We report here that vMIP-I is a specific agonist for the CC chemokine receptor (CCR)8 that is preferentially expressed on Th2 T cells. Y3 cells transfected with CCR8 produced a calcium flux in response to vMIP-I and responded vigorously in in vitro chemotaxis assays. In competition binding experiments, the interaction of vMIP-I with CCR8 was shown to be specific and of high affinity. In contrast to its agonist activity at CCR8, vMIP-I did not interact with CCR5 or any of 11 other receptors examined. Furthermore, vMIP-I was unable to inhibit CCR5-mediated HIV infection. These findings suggest that expression of vMIP-I by KSHV may influence the Th1/Th2 balance of the host immune response.
The Measurement of Extinction Coefficients Using a New Infrared Micropulse Reactor Technique: Adsorption of CO on Silica-Supported Pt (1982)

The increased sophistication in infrared instrumentation, coupled with recent advances in the limits of detection of commercially available gas chromatographs, has resulted in the revival of infrared spectroscopy as a useful tool in the study and characterization of supported-metal catalysts. In its initial applications, infrared spectroscopy was used as a tool in the surface characterization of supported-metal catalysts. The general procedure was to use a diatomic molecule, whose adsorptive behavior was well understood, as a surface probe to obtain information regarding the disposition of the underlying surface-metal atoms. In its more recent applications, it has become possible to observe the structure of adsorbed molecules under reaction conditions. For cases in which an infrared cell coupled to a gas chromatograph is used as a single-pass differential reactor, it is possible to measure reaction rates and to study the structure of the species adsorbed on the surface simultaneously. In studying the kinetics of surface reactions, it would be useful to have some knowledge of surface coverages under reaction conditions. This will ultimately enable investigators to test assumed mechanisms derived from experimentally determined rates by obtaining independent measurements of surface coverages. In order to do this quantitatively, it is necessary to measure extinction coefficients for both adsorbed reactants and products at process temperatures and pressures.
Manipulation of macrolide ring size by directed mutagenesis of a modular polyketide synthase (1995)

ADVERTISEMENT RETURN TO ISSUEPREVArticleManipulation of macrolide ring size by directed mutagenesis of a modular polyketide synthaseCamilla M. Kao, Guanglin Luo, Leonard Katz, David E. Cane, and C. KhoslaCite this: J. Am. Chem. Soc. 1995, 117, 35, 9105–9106Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://pubs.acs.org/doi/10.1021/ja00140a043https://doi.org/10.1021/ja00140a043research-articleACS PublicationsRequest reuse permissionsArticle Views674Altmetric-Citations164LEARN 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 (2)»Supporting Information Supporting Information Get e-Alerts
A Protective Role of the Low Density Lipoprotein Receptor-related Protein against Amyloid β-Protein Toxicity (2000)

In order to delineate the neuroprotective role of the low density lipoprotein receptor-related protein (LRP) against amyloid beta-protein toxicity, studies were performed in C6 cells challenged with amyloid beta-protein in the presence or absence of activated alpha(2)-macroglobulin. Toxicity was assessed via two cell viability assays. We found that this endocytic receptor conferred protection against amyloid beta-protein toxicity in the presence of activated alpha(2)-macroglobulin and its down-regulation via inhibition by receptor-associated protein or transfection of cells with presenilin 1, increased susceptibility to amyloid beta-protein toxicity. Increased surface LRP immunoreactivity in response to amyloid beta-protein challenge was associated with increased translocation of LRP from the endoplasmic reticulum to the surface, rather than from increased mRNA or protein expression. Furthermore, this translocation of LRP to the surface was mediated by a calcium/calmodulin protein kinase II-dependent signaling pathway. These studies provide evidence for a protective role of LRP against amyloid beta-protein toxicity and may explain the aggressive nature of presenilin-1 mutation in familial Alzheimer's disease.
Hypothyroidism during immunotherapy with interleukin-2 is associated with antithyroid antibodies and response to treatment. (1993)

The likelihood of developing (transient) hypothyroidism is higher in patients who respond to IL-2 treatment. The development of antithyroid antibodies suggests that IL-2 treatment triggers autoreactive B-cell clones or that cellular and/or cytokine-mediated thyroid destruction leads to activation of autoreactive B-cell clones.
The Kinase Activation Loop Is the Key to Mixed Lineage Kinase-3 Activation via Both Autophosphorylation and Hematopoetic Progenitor Kinase 1 Phosphorylation (2001)

We have demonstrated previously that Cdc42 induced MLK-3 homodimerization leads to both autophosphorylation and activation of MLK-3 and postulated that autophosphorylation is an intermediate step of MLK-3 activation following its dimerization. In this report we sought to refine further the mechanism of MLK-3 activation and study the role of the putative kinase activation loop in MLK-3 activation. First we mutated the three potential phosphorylation sites in MLK-3 putative activation loop to alanine in an effort to abrogate MLK-3 autophosphorylation. Mutant T277A displayed almost no autophosphorylation activity and was nearly nonfunctional; mutant S281A, that displayed a low level of autophosphorylation, only slightly activated its downstream targets, whereas the T278A mutant, that exhibited autophosphorylation comparable to that of the wild type, was almost fully functional. Thus, these residues within the activation loop are critical for MLK-3 autophosphorylation and activation. In addition, when the Thr277 and Ser281 residues were mutated to negatively charged glutamic acid to mimic phosphorylated serine/threonine residues, the resulting mutants were fully functional, implying that these two residues may serve as the autophosphorylation sites. Interestingly, HPK1 also phosphorylated MLK-3 activation loop in vitro, and Ser281 was found to be the major phosphorylation site, indicating that HPK1 also activates MLK-3 via phosphorylation of the kinase activation loop.
Evidence for a non-alpha-helical DNA-binding motif in the Rel homology region. (1994)

The Rel family of transcription factors serve as terminal messengers in a variety of developmental and receptor-mediated signaling pathways. These proteins are related by a domain of approximately 280 amino acids, the Rel homology region, which mediates dimerization and sequence-specific binding to DNA. Here we report the use of photocrosslinking and site-directed mutagenesis to identify specific contact partners in a Rel protein-DNA interface. Within the Rel homology region of NF-kappa B p50 (also known as KBF1), two amino acid residues were identified by photocrosslinking to adjacent bases in a beta-interferon regulatory element. Secondary structure analysis suggests that the DNA-binding motif of the Rel homology region comprises a beta-turn-beta structure, in contrast to the alpha-helical motifs so commonly observed in transcription factors.
Inhibition of phytohemagglutinin-induced lymphocyte mitogenesis by lipoxygenase metabolites of arachidonic acid: structure-activity relationships. (1984)

Phytohemagglutinin (PHA)-induced mitogenesis of mixed mouse spleen lymphocyte populations, measured by [3H]thymidine incorporation, was completely inhibited by micromolar concentrations of certain hydroxyeicosatetraenoic acids (HETE's). These are lipoxygenase metabolites of arachidonic acid which are synthesized in considerable concentrations by macrophages, lymphocytes, and other components of the immune system when appropriately stimulated. In the studies described here, the structural requirements for the maximum antimitogenic activities were examined. A series of monohydroxylated HETE's were prepared using a singlet oxygen photochemical procedure or by enzymatic synthesis from arachidonic acid substrate, and isolated by HPLC. Isomers containing different numbers of double bonds were synthesized using the appropriate unsaturated fatty acid as substrate, and the functional importance of the OH and carboxylic functions was tested using various acetoxy- and carbomethoxy derivatives. A serum-free mitogenesis assay system was used for testing, which minimized binding of the fatty acids by serum proteins and increased the inhibitory potency of the various HETE's several-fold. It was found that inhibition of cell proliferation was related to: hydroxyl proximity to the center of the eicosatetraenoic acid, decreasing in the order: 9 greater than 11 greater than 12 greater than 15 greater than 8 much greater than 5; the number of double bonds in the fatty acid chain, decreasing in the order: 15-OH, 20:4 greater than 15-OH 20:3 much greater than 15-OH, 20:2 much greater than 15-OH, 20:0; and the 15-position functional group as well as the 1-carboxylic group, decreasing in the order: 15-hydroxy, 1-carboxylic greater than 15-acetoxy, 1-carboxylic much greater than 15-hydroxy, 1-carbomethoxy greater than 15-acetoxy, 1-carbomethoxy.(ABSTRACT TRUNCATED AT 250 WORDS)
Regulation of insulin action at the cellular level. (1991)

Insulin regulates cellular metabolic reactions by its action on the plasma membrane, intracellular enzymes and the nucleus. The first stage in the propagation of the insulin signal is the coupling of insulin to specific receptors at the cell surface. The exact mechanism whereby the transmembrane signalling mechanism (s) results in different insulin-mediated cellular effects is not known. However, the insulin receptor tyrosine kinase, the expression of second messengers, and the action of protein kinase C may, either individually or in combination, mediate some of the insulin effects, such as translocation and activation of glucose transporter proteins. Insulin resistance in clinical conditions such as insulin-dependent diabetes mellitus (IDDM), non-insulin-dependent diabetes mellitus (NIDDM), hypertension and obesity may be acquired to a large extent, and is thus partially reversible. Regulatory factors in insulin sensitivity, such as free fatty acids, counterregulatory hormones and blood glucose level, play an important role in the metabolic control and pathogenesis of insulin resistance in man.
Introduction (1979)

This is a history of the Bolsheviks and their organisational development in the early era of the Soviet state. It is not an act of homage to certain leaders or factions. Nor is it an exercise in demonology. Its collective subject is the Bolshevik party as a political and social whole, as a total organisation in pursuit of revolutionary change in the former Russian empire. Its unifying theme is an internal metamorphosis. The Bolsheviks passed through a momentous transformation, organisationally as well as politically, within half a dozen years of seizing power through the October Revolution. Attitudes and behaviour which had seemed so deeply embedded in the party of 1917 were to disappear forever by 1923. The shockwaves of the process spread out far beyond the limits of the period and the boundaries of the Soviet Union. The following chapters seek to describe and explain what happened.KeywordsCentral CommitteeSoviet StateOctober RevolutionDiscipline PartyAuthoritarian MethodThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Human Fc gamma Receptor IIb Expressed in <I>Escherichia coli</I> Reveals IgG Binding Capability (1999)

Fcgamma receptors (FcgammaR) are expressed on immunologically active cells where they trigger B and T cell responses and are responsible for the clearance of immunocomplexes. They occur as type I transmembrane proteins and also in soluble forms (sFcR) comprising only the ecto domains of the receptors. State-of-the-art research has generated demand for highly pure and homogeneous sFcgammaR preparations: first, studies of the immunoregulative potential of the soluble FcgammaRs have been hampered by co-purified growth factors. Second, they are needed for crystallographic analyses to solve questions such as the exact location of the binding site for IgG on the receptor, and the graded affinities of the receptors for different IgG subclasses. This has been unsuccessful due to limitations in availability and homogeneity of sFcgammaR expressed in eukaryotic cells. In order to address these problems we expressed the extracellular part of the human FcgammaRIIb in E. coli. The protein was refolded, purified in a three-step procedure and characterized by SDS-PAGE, mass spectrometry as well as N-terminal sequencing. The unglycosylated FcgammaRIIb is active because it binds immobilized antibody as well as the IgG Fc-fragment in solution. Finally, the receptor was crystallized in orthorhombic, tetragonal and hexagonal crystal forms that diffracted X-rays to resolutions of 1.7 A, 2.7 A and 3.8 A respectively.