gebhart/patrepeval huggingface dataset:
Drug treatment of Alzheimer’s disease (2002)

Alzheimer’s disease (AD) is an international problem of enormous significance. The human and financial cost to the sufferers, their families and friends is huge, matched by the costs to health and social services in all developed countries and, increasingly, elsewhere.
A Comparison of U.S. and E.U. Product Safety Regulations: A Case Study (1997)

Mr. Harris compares government approaches with respect to foods that are combined with, e.g., trinkets - particularly when likely to be consumed by children.
Discussion (1997)

w x We recently reported in this journal 1 that intravenous administration of adenosine, given immediately prior to and continuing for 2.5 h into reperfusion, failed to limit infarct size in an open-chest canine model of regional myocardial infarction. Our study was designed to investigate the ability of adenosine, one putative inhibitor of lethal reperfusion injury, to limit myocardial necrosis following a regional ischemic insult. Both lethal and nonlethal reperfusion injury have been hypothesized to exist. There is strong evidence that myocardial stunning occurs, at least in part, through oxygen-derived free radicals generated upon the onset of arterial reperfusion and therefore stunning is generally accepted to be a form of non-lethal w x reperfusion injury 2 . However, the existence of lethal reperfusion injury is more controversial. The experimental protocol used in our study included therapy with adenosine, based on the dose, route, and timing of administration used in the study of Pitarys et al. w x Ž 3 . These investigators had reported a positive effect i.e., . limitation of infarct size of therapy in a closed-chest canine model. In addition, our experimental protocol was designed to reproduce the results previously reported by Homeister et al. who showed that adenosine plus bolus administration of lidocaine, but not adenosine alone, resulted in cardioprotection in a canine model of regional w x infarction 4 . We were unable to show any limitation of infarct size as a result of intravenous adenosine administration, with or without lidocaine, in our open-chest model. Our negative results were discordant with the reports of marked limitation of infarct size in studies by Forman and w x colleagues 3 . Both openand closed-chest models have been used successfully in many different experimental laboratories to w x study the pathophysiology of ischemia and reperfusion 5 .
Ancora sui termini "peronismo" e "giustizialismo": dal Sudamerica all'Italia, e ritorno (2004)

The essay reports the remarks of many Latin American and Spanish authors who refer to the essay (published on «Teoria Politica», 2003, n. 1, pp. 3-22) devoted to analyzing the terms «peronism», «justicialismo», «regime», «populism» etc. Extended quotations translated into Italian and divided by topic underline the anomalies in the Italian usage of these terms and offer examples related to the Spanish usage. The essay opens with an analysis of the evolution and involution of political language under European dictatorships. Particularly relevant are the different and often conflicting opinions on the tightness of the relationship between peronism and fascism, and the final remarks on Peron Uruguayan origins.
New PDC Bit Technology, Improved Drillability Analysis, and Operational Practices Improve Drilling Performance in Hard and Highly Heterogeneous Applications (2004)

Abstract The application envelopes of PDC bits have conventionally been defined by rock hardness. Although technologies1,2, 3, 4 aimed at improving PDC bit efficiencies in challenging drilling environments continue to be developed, performances in such applications still lack consistency. It has become apparent, from drilling performance evaluations, that formation hardness alone can not be used to categorize PDC bits. In some instances, PDC bit performances have varied profoundly across given fields, even when formation types and tops, lithologies and hardness have been determined to be comparable. These performance differences, which continue to baffle the industry, amplify with increasing formation heterogeneity especially in hard rock environments. This paper will present a three part process, which has been developed to address the challenges described above. First a new approach, which characterizes rocks by their drilling difficulty, is used to establish field trends. Considering offsets, or anticipated performance requirements, bit development and/or selection is done with the aid of two new parameters – stress and durability equivalencies. Finally, operational practices aimed at enhancing the effectiveness of this new process are developed and implemented. This paper will quantify and discuss the individual and combined effects of these processes. Analytical, laboratory and field data, showing the effectiveness of this new methodology, will be presented.
Polymorphisms generated by arbitrarily primed PCR in the mouse: application to strain identification and genetic mapping (1991)

Polymorphisms in genomic fingerprints generated by arbitrarily primed PCR (AP-PCR) can distinguish between strains of almost any organism. We applied the technique to the mouse (Mus musculus). The characteristic differences in the AP-PCR genomic fingerprints between strains will be of value in strain identification and verification. Using one primer, we genetically mapped four polymorphisms in a set of C57BL/6J x DBA/2J recombinant inbreds. One of these polymorphisms is a length variant. The method will allow rapid genetic mapping of DNA polymorphisms without Southern blotting.
Cloning of Babesia bovis by in vitro cultivation (1983)

A procedure for cloning Babesia bovis was developed. The procedure was used to establish and cultivate homogeneous populations of parasites and to isolate B. bovis from carrier animals. Three different clone lines of B. bovis based on in vitro growth rates were established.
Formulation of enamel matrix derivative for surface coating (1997)

Enamel Matrix Derivative (EMD) contains a protein complex belonging to the amelogenin family. Enamel matrix as well as EMD have been found to promote periodontal regeneration when applied onto denuded root surfaces in dehiscence models. In the present studies it is shown that propylene glycol alginate (PGA) is a suitable vehicle for EMD for its local application. EMD can be dissolved in PGA at an acidic pH, resulting in a highly viscous solution. At neutral pH and body temperature the viscosity decreases and EMD precipitates. Multilayers of EMD on mineral or protein surfaces have been analysed using ellipsometry, total internal reflection fluorescence (TIRF) and biospecific interaction analysis (BIA). The studies show that EMD adsorbs both to hydroxyapatite and collagen and to denuded dental roots. It forms insoluble spherical complexes, and detectable amounts remain at the site of application on the root surface for two weeks, as shown with radiolabelled protein in rats and pigs. Scanning electron micrograph (SEM) studies on monkey teeth further indicate that EMD in PGA may promote repopulation of fibroblast-like cells during the first weeks after application.
Effects of Sequence of Thioated Oligonucleotides on Cultured Human Mammary Epithelial Cells (1993)

We have compared the effects of a number of different oligonucleotides on the growth and morphology of normal finite life span and immortally transformed human mammary epithelial cells. The oligonucleotide sequences chosen initially for study were based on that of the NB-1 gene, which encodes a calmodulin-like protein of unknown function. We found that certain thioated oligonucleotides 15-20 residues in length altered the morphology and decreased the growth rate of the normal cells in a concentration-dependent manner. These effects were rapid, occurring within 24-48 h of oligonucleotide addition. The effects, which occurred without an accompanying detectable decrease in the levels of NB-1 mRNA or protein, were most pronounced in the normal epithelial cells, less apparent in the immortalized epithelial cells, and unobserved in normal breast fibroblasts. Identical sequences having mixed phosphodiester and phosphorothioate backbones, or phosphodiester backbones alone, had little or no effect on normal epithelial cell morphology or growth. Two out of seven additional thioated oligonucleotides which were not complementary to NB-1 mRNA, also affected normal epithelial cell morphology and growth when used at similar concentrations (10 microM). Taken together, the observed effects on normal epithelial cells indicate that certain thioated oligonucleotides may have pharmacological consequences that do not depend on strict complementarity of their sequences to known mRNAs.
The crystallographically determined structures of atypical strained disulfides engineered into subtilisin. (1986)

The geometries of two disulfide bridges genetically engineered into subtilisin have been characterized by x-ray crystallography to determine the structural and energetic constraints involved in introducing disulfide bonds into proteins. Both disulfide bridges (Cys-24-Cys-87 and Cys-22-Cys-87) exhibit atypical sets of dihedral angles compared to those for other reported disulfide structures in proteins. The geometric trends for naturally occurring disulfides in protein crystal structures are examined. Comparison of the disulfide-containing mutant protein structures with the wild-type structure shows that, in both cases, disulfide incorporation is accommodated by relatively minor changes in local main-chain conformation. The Cys-22-Cys-87 disulfide has two high energy dihedral angles (X2 = 121 degrees, X2' = 143 degrees). Both disulfides produce short non-bonded contacts with the main-chain.
Ca2+ concentration during binding determines the manner in which annexin V binds to membranes (1995)

Annexins are a family of calcium-binding proteins that have been implicated in a wide range of intracellular processes. We have previously reported that stimulation of platelets with thrombin can induce the association of intracellular annexin V with membranes in two distinct ways. First, in such a way that it can be eluted from the membrane with EGTA and secondly in a manner such that it is tightly bound to the membrane and requires the non-ionic detergent Triton X-100 for its solubilization. We report that exposure of platelets to the calcium ionophore A23187 mimics the relocation induced by stimulation with thrombin. In separate experiments we demonstrate that a calcium ion concentration [Ca2+] of 0.8 microM is sufficient for maximum binding of the EGTA-resistant form to membranes. In contrast a higher [Ca2+] was required to induce maximal binding of the annexin V which could be extracted with EGTA. We demonstrate that following temperature-induced phase separation in Triton X-114, the membrane-associated annexin V partitions predominantly into the aqueous phase. We also show that the isoelectric point of annexin V does not change following membrane association. These observations suggest that a covalent modification, of annexin V itself, is not responsible for its association with the membrane. Millimolar [Ca2+] is required for maximal binding of purified annexin V to phospholipid vesicles. We show that binding to phospholipids can be reversed entirely by subsequent treatment with EGTA. This suggests that the EGTA-resistant form of annexin V is binding to a membrane component other than phosphatidylserine. Annexin V has previously been shown to bind to protein kinase C. Relocation of annexin V to membranes paralleled that of protein kinase C in thrombin-stimulated cells but not in cells treated with A23187, suggesting that these proteins are not functionally linked in platelet activation. Using bifunctional cross-linking reagents we have identified an 85 kDa complex containing annexin V. This may represent an association between annexin V and an annexin V-binding protein with a molecular mass of approximately 50 kDa.
Mitral and Tufted Cells Are Potential Cellular Targets of Nitration in the Olfactory Bulb of Aged Mice (2013)

Olfactory sensory function declines with age; though, the underlying molecular changes that occur in the olfactory bulb (OB) are relatively unknown. An important cellular signaling molecule involved in the processing, modulation, and formation of olfactory memories is nitric oxide (NO). However, excess NO can result in the production of peroxynitrite to cause oxidative and nitrosative stress. In this study, we assessed whether changes in the expression of 3-nitrotyrosine (3-NT), a neurochemical marker of peroxynitrite and thus oxidative damage, exists in the OB of young, adult, middle-aged, and aged mice. Our results demonstrate that OB 3-NT levels increase with age in normal C57BL/6 mice. Moreover, in aged mice, 3-NT immunoreactivity was found in some blood vessels and microglia throughout the OB. Notably, large and strongly immunoreactive puncta were found in mitral and tufted cells, and these were identified as lipofuscin granules. Additionally, we found many small-labeled puncta within the glomeruli of the glomerular layer and in the external plexiform layer, and these were localized to mitochondria and discrete segments of mitral and tufted dendritic plasma membranes. These results suggest that mitral and tufted cells are potential cellular targets of nitration, along with microglia and blood vessels, in the OB during aging.
Microfluidic Digital PCR Enables Multigene Analysis of Individual Environmental Bacteria (2006)

Gene inventory and metagenomic techniques have allowed rapid exploration of bacterial diversity and the potential physiologies present within microbial communities. However, it remains nontrivial to discover the identities of environmental bacteria carrying two or more genes of interest. We have used microfluidic digital polymerase chain reaction (PCR) to amplify and analyze multiple, different genes obtained from single bacterial cells harvested from nature. A gene encoding a key enzyme involved in the mutualistic symbiosis occurring between termites and their gut microbiota was used as an experimental hook to discover the previously unknown ribosomal RNA-based species identity of several symbionts. The ability to systematically identify bacteria carrying a particular gene and to link any two or more genes of interest to single species residing in complex ecosystems opens up new opportunities for research on the environment.
Anti‐interleukin‐6 receptor antibody, tocilizumab, for the treatment of autoimmune diseases (2011)

Interleukin (IL)-6 is a cytokine with multiple biological activities. It contributes to host defense against pathogens, whereas accelerated production of IL-6 plays a significant pathological role in various diseases. Clinical trials have demonstrated the efficacy of tocilizumab, a humanized anti-IL-6 receptor antibody, for patients with rheumatoid arthritis, Castleman's disease or juvenile idiopathic arthritis, leading to approval of this innovative drug for the treatment of these diseases. Since IL-6 has been demonstrated to play a significant role in the development of various other autoimmune and inflammatory diseases, tocilizumab can be expected to become a novel drug for such diseases as well.
The Mechanism of Dephosphorylation of Extracellular Signal-regulated Kinase 2 by Mitogen-activated Protein Kinase Phosphatase 3 (2001)

The mitogen-activated protein (MAP) kinase phosphatase-3 (MKP3) is a dual specificity phosphatase that specifically inactivates one subfamily of MAP kinases, the extracellular signal-regulated kinases (ERKs). Inactivation of MAP kinases occurs by dephosphorylation of Thr(P) and Tyr(P) in the TXY kinase activation motif. To gain insight into the mechanism of ERK2 inactivation by MKP3, we have carried out an analysis of the MKP3-catalyzed dephosphorylation of the phosphorylated ERK2. We find that ERK2/pTpY dephosphorylation by MKP3 involves an ordered, distributive mechanism in which MKP3 binds the bisphosphorylated ERK2/pTpY, dephosphorylates Tyr(P) first, dissociates and releases the monophosphorylated ERK2/pT, which is then subjected to dephosphorylation by a second MKP3, yielding the fully dephosphorylated ERK2. The bisphosphorylated ERK2 is a highly specific substrate for MKP3 with a k(cat)/K(m) of 3.8 x 10(6) m(-1) s(-1), which is more than 6 orders of magnitude higher than that for small molecule aryl phosphates and an ERK2-derived phosphopeptide encompassing the pTEpY motif. This strikingly high substrate specificity displayed by MKP3 may result from a combination of high affinity binding interactions between the N-terminal domain of MKP3 and ERK2 and specific ERK2-induced allosteric activation of the MKP3 C-terminal phosphatase domain.
Alicyclic Claisen rearrangement. A general carbocycle synthesis based on four-atom-ring contractions of lactones (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAlicyclic Claisen rearrangement. A general carbocycle synthesis based on four-atom-ring contractions of lactonesMatthew M. Abelman, Raymond L. Funk, and John D. Munger Jr.Cite this: J. Am. Chem. Soc. 1982, 104, 14, 4030–4032Publication Date (Print):July 1, 1982Publication History Published online1 May 2002Published inissue 1 July 1982https://pubs.acs.org/doi/10.1021/ja00378a054https://doi.org/10.1021/ja00378a054research-articleACS PublicationsRequest reuse permissionsArticle Views672Altmetric-Citations60LEARN 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
Efficient isolation of genes by using antibody probes. (1983)

A sensitive and general technique has been devised for the dual purposes of cloning genes by using antibodies as probes and isolating unknown proteins encoded by cloned DNA. The method uses an expression vector, lambda gt11 (lac5 nin5 cI857 S100), that permits insertion of foreign DNA into the beta-galactosidase structural gene lacZ and promotes synthesis of hybrid proteins. Efficient screening of antigen-producing clones in lambda gt11 recombinant cDNA libraries is achieved through lysogeny of the phage library in hflA (high-frequency lysogeny) mutant cells of Escherichia coli; lysogens produce detectable quantities of antigen on induction, even when plated at high cell densities. The vector is also designed to facilitate the isolation of proteins specified by previously cloned gene sequences. Hybrid proteins encoded by recombinant phage accumulate in strains defective in protein degradation (lon mutants) in amounts amenable to large-scale purification. Antibodies produced against the portion of the hybrid encoded by foreign DNA could in turn be used to isolate the native polypeptide from eukaryotic cells.
Inhibitors of tyrosine kinase (1997)

This review covers the literature on significant studies of small molecule inhibitors of the epidermal growth factor receptor (EGFR), platelet-derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), Flk-1, and src family tyrosine kinases from 1996 through mid-1997. During this period, there has been substantial progress in the discovery of new and highly specific tyrosine kinase inhibitors (TKIs), particularly for the EGFR family. The last 18 months saw a focused effort to discover tyrosine kinase inhibitors with increased potency, increased selectivity, better animal pharmacokinetics, and decreased toxicity. Indeed, some EGFR TKIs are now in clinical trials or are about to enter clinical trials as potential anticancer agents. Potent and selective kinase inhibitors have also been described for PDGFR, but none of these compounds have appeared to advance in the developmental process as far as kinase inhibitors for the EGFR family. Surprisingly, potent and selective inhibitors of receptors involved in neovascularization such as FGFR, Flk-1, or Flt-1 are less prevalent in the literature, and the discovery of TKIs that can inhibit angiogenesis remains a fertile area for drug discovery. Tyrosine kinases continue to remain an extremely attractive target for the design of potent and selective inhibitors that will represent an important new class of therapeutic agents for the treatment of a variety of diseases where current therapy is still insufficient.
Estrogen Receptor α Regulates Expression of the Orphan Receptor Small Heterodimer Partner (2003)

Hormonal status can influence diverse metabolic pathways. Small heterodimer partner (SHP) is an orphan nuclear receptor that can modulate the activity of several transcription factors. Estrogens are here shown to directly induce expression of the SHP in the mouse and rat liver and in human HepG2 cells. SHP is rapidly induced within 2 h following treatment of mice with ethynylestradiol (EE) or the estrogen receptor alpha (ERalpha)-selective compound propyl pyrazole triol (PPT). SHP induction by these estrogens is completely absent in ERalphaKO mice. Mutation of the human SHP promoter defined HNF-3, HNF-4, GATA, and AP-1 sites as important for basal activity, whereas EE induction required two distinct elements located between -309 and -267. One of these elements contains an estrogen response element half-site that bound purified ERalpha, and ERalpha with a mutated DNA binding domain was unable to stimulate SHP promoter activity. This ERalpha binding site overlaps the known farnesoid X receptor (FXR) binding site in the SHP promoter, and the combination of EE plus FXR agonists did not produce an additive induction of SHP expression in mice. Surprisingly, induction of SHP by EE did not inhibit expression of the known SHP target genes cholesterol 7alpha-hydroxylase (CYP7A1) or sterol 12alpha-hydroxylase (CYP8B1). However, the direct regulation of SHP expression may provide a basis for some of the numerous biological effects of estrogens.
Advanced dual beam laser welding of zinc-coated steel sheets in lap joint configuration with zero gap at the interface (2004)

A new concept for dual beam laser lap joining of galvanized steel sheets with zero gap at the interface is presented. This concept employs two laser beams with an angle between them. The new laser beam configuration is implemented by combining two laser focusing heads through use of a custom designed fixture. Welding trials were conducted with a robot by mounting the whole beam delivery set-up at the end of the robot arm. Excellent quality welds were obtained on a variety of zinc-coated sheet combinations. This paper focuses on the results obtained on 1.4/1.4 mm hot dipped galvanized steel sheets. The effects of various welding parameters were studied through both experimental trials as well as modeling of the keyhole geometry.