gebhart/patrepeval huggingface dataset:
Rapid in vitro selection of human immunodeficiency virus type 1 resistant to 3'-thiacytidine inhibitors due to a mutation in the YMDD region of reverse transcriptase. (1993)

Resistant variants of human immunodeficiency virus type 1 (HIV-1) have been selected by limited passage in MT4 cells of both wild-type and 3'-azido-3'-deoxythymidine (AZT, zidovudine)-resistant strains with the nucleoside analogues (-)-2'-deoxy-3'-thiacytidine (3TC) and (-)-2'-deoxy-5-fluoro-3'-thiacytidine (FTC). Virus variants selected independently were crossresistant to both inhibitors. This rapid in vitro selection of resistant virus has not previously been seen with nucleoside analogues but is reminiscent of that observed with the nonnucleoside reverse transcriptase inhibitors. However, passage of wild-type virus with a combination of AZT and FTC appreciably delayed emergence of FTC-resistant virus. DNA sequence analysis of the reverse transcriptase coding region from FTC-resistant virus revealed changes at codon 184 in the highly conserved Tyr, Met, Asp, Asp (YMDD) region. When the mutation Met184-->Val was introduced into the infectious clone HXB2, this change alone accounted for the resistance (> 1000-fold) seen with both 3TC and FTC, and for a 5- to 15-fold reduction in sensitivity to their (+) enantiomers. It had no effect on susceptibility to AZT or nevirapine and minimal effect on susceptibility to 2',3'-dideoxyinosine and 2',3'-dideoxycytidine. To determine the influence of this mutation in a background of mutations conferring resistance to AZT and nonnucleoside reverse transcriptase inhibitors, a series of HIV-1 variants were created by site-directed mutagenesis. All mutants with Met184-->Val were cross-resistant to 3TC and FTC. The Met184-->Val mutation did not influence nevirapine resistance, but resistance to AZT was suppressed. Similar suppression of AZT resistance was seen with Tyr181-->Cys. Interestingly, when both Met184-->Val and Tyr181-->Cys substitutions were present, highly resistant virus reverted to complete AZT sensitivity. Assessment of the interactive effects of multiple drug-resistance mutations may help to establish a rationale for using these drugs in the future therapy of HIV disease.
Andreev reflections and resonance tunneling in Josephson junctions (1995)

The current-voltage characteristics (I-V) and Josephson critical current for the tunneling junctions with the resonant levels in the weak link are calculated. It seems likely that the current in these structures occurred due to resonant tunneling through a localized state. This resonant state effects the formation of long-range proximity effect. The subgap structure that appears on I-V characteristic of such junctions is caused by multiple Andreev reflections of quasiparticles at the interfaces. The I-V dependence is calculated for different values of the resonance parameter. This parameter is proportional to the ratio of the escape of the quasiparticle from the localized state into the superconducting electrodes. It is then shown that the larger subgap current corresponds to a smaller value of the resonant parameter.
Synthesis of a Fluorogenic Analogue of Sphingosine‐1‐Phosphate and Its Use to Determine Sphingosine‐1‐Phosphate Lyase Activity (2009)

Abstract Illuminating an ER enzyme : We report on the design and synthesis of a fluorogenic chemical sensor ( 1 ) to measure sphingosine‐1‐phosphate lyase activity in high‐throughput screening formats, as well as its validation using lyase knockout ( Sgpl1−/− ) cells. magnified image
Effects of Age, Education, and Gender on Domain-specific Cogntive Scores on the Mini-Mental State Examination-K1 (2012)

Purpose: This study was done to examine the effects of age, education, and gender on 7 cognitive components of Mini-Mental State Examination-Korean version 1 (MMSE-K1). Methods: Effects of age, education, and gender on 7 cognitive components of MMSE-K1 were analyzed using descriptive statistics and correlation coefficient with Statistical Package for the Social Sciences (SPSS) 18.0 program. Participants were 740 Korean middle-aged and older adults. Partial correlations were computed to control for significant correlations among demographic variables. Results: Effects of age ranged from 0.0 to 7.0% across 7 cognitive components of MMSE-K1 and were highest in the component of orientation for time. Effects of education ranged from 0.5 to 21.5% across 7 cognitive components and tended to be higher for attention & calculation. Effects of gender ranged from .0 to .5% across 7 cognitive components and were relatively high in measures of information (male > female) except for registration (female > male). Total effects of age, education and gender ranged from 1.1 to 32.5%. Conclusion: These results provided useful information about MMSE-K1 when it is used as a screening instrument for dementia. Also the findings should contribute to early detection, prevention and prognosis assessment of dementia in middle-aged and elderly people.
Organic Field-effect Transistors Based on Solution-processible Dibenzotetrathiafulvalene Derivatives (2009)

Abstract Organic field-effect transistors based on alkyl-substituted dibenzotetrathiafulvalenes (DBTTF) are fabricated by solution process. The molecules with butyl or longer alkyl groups are standing perpendicular to the substrates in the thin films, and the transistors exhibit comparable performance to the vacuum-deposited DBTTF devices.
Fabrication of Bond and Etch‐Back Silicon on Insulator Using a Strained Si0.7Ge0.3 Layer as an Etch Stop (1990)

Bond and etch‐back silicon on insulator was fabricated using a strain‐selective etch and a novel etch stop consisting of a strained layer deposited by molecular beam epitaxy. The process was used to fabricate a 200–350 nm silicon layer on insulator. A 350‐nm silicon film on insulator fabricated by this technique was very lightly p‐type with a carrier density of less than 1015 cm−3.
A practical synthesis of long-chain iso-fatty acids (iso-C12–C19) and related natural products (2013)

A gram-scale synthesis of terminally-branched iso-fatty acids (iso-C12-C19) was developed commencing with methyl undec-10-enoate (methyl undecylenate) (for iso-C12-C14) or the C15 and C16 lactones pentadecanolide (for iso-C15-C17) and hexadecanolide (for iso-C18-C19). Central to the approaches outlined is the two-step construction of the terminal isopropyl group through addition of methylmagnesium bromide to the ester/lactones and selective reduction of the resulting tertiary alcohols. Thus, the C12, C17 and C18 iso-fatty acids were obtained in three steps from commercially-available starting materials, and the remaining C13-C16 and C19 iso-fatty acids were prepared by homologation or recursive dehomologations of these fatty acids or through intercepting appropriate intermediates. Highlighting the synthetic potential of the iso-fatty acids and various intermediates prepared herein, we describe the synthesis of the natural products (S)-2,15-dimethylpalmitic acid, (S)-2-hydroxy-15-methylpalmitic acid, and 2-oxo-14-methylpentadecane.
Cardioprotective and endothelial protective effects of [Ala‐IL8]77 in a rabbit model of myocardial ischaemia and reperfusion (1991)

1 We studied the effects of a form of interleukin-8 (i.e., [Ala-IL8]77) on endothelial dysfunction and myocardial injury in rabbits. Pentobarbitone-anaesthetized rabbits were subjected to 1.5 h occlusion of the marginal coronary artery and 3.5 h reperfusion. [Ala-IL8]77 (50 micrograms or its vehicle) was given i.v. as a bolus 10 min prior to reperfusion. [Ala-IL8]77 was also studied in isolated perfused hearts of rabbits. 2 Myocardial ischaemia plus reperfusion in untreated rabbits produced severe endothelial dysfunction and myocardial injury, including marked myocardial necrosis, elevated cardiac myeloperoxidase (MPO) activity in ischaemic cardiac tissue, and loss of response of marginal coronary rings to the endothelium-dependent vasodilators, acetylcholine (ACh) and A23187. 3 Administration of [Ala-IL8]77 10 min prior to reperfusion resulted in significant protective effects in post-ischaemic reperfusion. Compared with untreated rabbits, [Ala-IL8]77 caused a reduced necrotic zone (P less than 0.01), lower MPO activity in the necrotic zone (P less than 0.05), and significantly preserved vasorelaxant responses of marginal coronary artery rings to endothelium-dependent vasodilators, ACh (P less than 0.001) and A23187 (P less than 0.001). 4 These results indicate that myocardial ischaemia and reperfusion result in a severe endothelial dysfunction and myocardial injury which involved the interaction of neutrophils and endothelial cells. However, [Ala-IL8]77 did not appear to exert a direct endothelial protective effect in the absence of neutrophils in rabbit isolated perfused hearts. 5 Inhibition of neutrophil accumulation in the myocardium, perhaps by prevention of endothelial dysfunction resulting from [Ala-IL8]77, leads to significant protective effects in ischaemia and reperfusion in rabbits.
Definition of receptor binding sites on human interleukin‐11 by molecular modeling‐guided mutagenesis (1999)

Interleukin-11 (IL-11) belongs to the interleukin-6 (IL-6)-type subfamily of long-chain helical cytokines including IL-6, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), oncostatin M, and cardiotrophin-1, which all share the glycoprotein gp130 as a signal transducing receptor component. IL-11 acts on cells expressing gp130 and the IL-11 receptor (IL-11R) alpha-subunit (IL-11Ralpha). The structural epitopes of IL-11 required for the recruitment of the individual receptor subunits have not yet been defined. Based on the structure of CNTF, a three-dimensional model of human IL-11 was built. Using this model, 10 surface exposed amino acid residues of IL-11 were selected for mutagenesis using analogies to the well-characterized receptor recruitment sites of IL-6, CNTF, and LIF. The respective mutants of human IL-11 were expressed as soluble fusion proteins in bacteria. Their biological activities were determined on HepG2 and Ba/F3-130-11alpha cells. Several mutants with substantially decreased bioactivity and one hyperagonistic mutant were identified and further analyzed with regard to recruitment of IL-11Ralpha and gp130. The low-activity mutant I171D still binds IL-11Ralpha but fails to recruit gp130, whereas the hyperagonistic variant R135E more efficiently engages the IL-11R subunits. The low-activity mutants R190E and L194D failed to bind to IL-11Ralpha. These findings reveal a common mechanism of receptor recruitment in the family of IL-6-type cytokines and offer considerable perspectives for the rational design of IL-11 antagonists and hyperagonists.
Mitogen-activated protein kinases regulate vascular reactivity after hemorrhagic shock through myosin light chain phosphorylation pathway (2013)

BACKGROUND Vascular hyporeactivity played an important role in many critical illness including shock or sepsis, but the mechanisms are incompletely understood. The objective of the present study was to investigate the roles of major mitogen-activated protein kinases (MAPKs extracellular signal-regulated kinase [ERK], p38 MAPK, and jun NH2-terminal kinase [JNK]) on vascular reactivity and the mechanisms. METHODS With superior mesenteric arteries from hemorrhagic shock rats, the role of p38 MAPK, ERK, and JNK in the regulation of vascular reactivity following shock and their relationship to myosin light chain (MLC20) phosphorylation–dependent pathway was observed. RESULTS ERK, p38 MAPK, and JNK activities in superior mesenteric arteries were increased at early shock and decreased at late shock. Stimulation of MAPKs with angiotensin II (AngII) increased the vascular reactivity, calcium sensitivity, and MLC20 phosphorylation. The increasing effect of AngII on vascular reactivity was antagonized by ERK, p38 MAPK, and JNK inhibitors, while the effect of AngII on calcium sensitivity was only blocked by ERK and p38 MAPK inhibitor, but not by JNK inhibitor. AngII increased the activity of protein kinase C–dependent phosphatase inhibitor of 17-kD (CPI17), integrin-linked kinase (ILK), and zipper-interacting protein kinase (ZIPK), The effect of AngII on CPI17 was blocked by ERK and p38 MAPK inhibitor, while the effect of AngII on ILK and ZIPK was only blocked by ERK inhibitor. CONCLUSION MAPKs participated in the regulation of vascular reactivity during shock. ERK and p38 MAPK is mainly through ILK, ZIPK, and CPI17-mediated MLC20 phosphorylation–dependent pathway, while JNK may be involved in the regulation of vascular reactivity by other mechanisms.
Cross-Linking of Bovine Pancreatic Ribonuclease A with Dimethyl Adipimidate* (1967)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCross-Linking of Bovine Pancreatic Ribonuclease A with Dimethyl Adipimidate*Fred C. Hartman and Finn WoldCite this: Biochemistry 1967, 6, 8, 2439–2448Publication Date (Print):August 1, 1967Publication History Published online1 May 2002Published inissue 1 August 1967https://pubs.acs.org/doi/10.1021/bi00860a021https://doi.org/10.1021/bi00860a021research-articleACS PublicationsRequest reuse permissionsArticle Views211Altmetric-Citations100LEARN 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
Resonant Metalenses for Breaking the Diffraction Barrier (2010)

We introduce the resonant metalens, a cluster of coupled subwavelength resonators. Dispersion allows the conversion of subwavelength wave fields into temporal signatures while the Purcell effect permits an efficient radiation of this information in the far field. The study of an array of resonant wires using microwaves provides a physical understanding of the underlying mechanism. We experimentally demonstrate imaging and focusing from the far field with resolutions far below the diffraction limit. This concept is realizable at any frequency where subwavelength resonators can be designed.
High-Yield Resveratrol Production in Engineered Escherichia coli (2011)

Plant polyphenols have been the subject of several recent scientific investigations since many of the molecules in this class have been found to be highly active in the human body, with a plethora of health-promoting activities against a variety of diseases, including heart disease, diabetes, and cancer, and with even the potential to slow aging. Further development of these potent natural therapeutics hinges on the formation of robust industrial production platforms designed using specifically selected as well as engineered protein sources along with the construction of optimal expression platforms. In this work, we first report the investigation of various stilbene synthases from an array of plant species considering structure-activity relationships, their expression efficiency in microorganisms, and their ability to synthesize resveratrol. Second, we looked into the construct environment of recombinantly expressed stilbene synthases, including different promoters, construct designs, and host strains, to create an Escherichia coli strain capable of producing superior resveratrol titers sufficient for commercial usage. Further improvement of metabolic capabilities of the recombinant strain aimed at improving the intracellular malonyl-coenzyme A pool, a resveratrol precursor, resulted in a final improved titer of 2.3 g/liter resveratrol.
A stencil compiler for short-vector SIMD architectures (2013)

Stencil computations are an integral component of applications in a number of scientific computing domains. Short-vector SIMD instruction sets are ubiquitous on modern processors and can be used to significantly increase the performance of stencil computations. Traditional approaches to optimizing stencils on these platforms have focused on either short-vector SIMD or data locality optimizations. In this paper, we propose a domain specific language and compiler for stencil computations that allows specification of stencils in a concise manner and automates both locality and short-vector SIMD optimizations, along with effective utilization of multi-core parallelism. Loop transformations to enhance data locality and enable load-balanced parallelism are combined with a data layout transformation to effectively increase the performance of stencil computations. Performance increases are demonstrated for a number of stencils on several modern SIMD architectures.
Telomerase Alone Extends the Replicative Life Span of Human Skeletal Muscle Cells Without Compromising Genomic Stability (2003)

Continuous cycles of muscle fiber necrosis and regeneration are characteristic of the muscular dystrophies, and in some cases this leads to premature replicative senescence of myoblasts in vitro. The molecular mechanism of senescence in human myoblasts is poorly understood but there is evidence to suggest that telomeric attrition may be one of the ways by which this is achieved. We report here, for the first time, the extension of normal human skeletal muscle cell replicative life span by the reconstitution of telomerase activity. The telomerase-expressing cells show no features of transformation in vitro and have stable genomes with diploid karyotypes, do not express exceptionally high levels of c-myc and have wild-type, unmethylated CDKN2A genes. In vivo, they regenerate to repair muscle injury in immunosuppressed RAG-1 mice. This work suggests that telomerase expression to repair short telomeres may aid the expansion of diploid human muscle cells and consequently attempts at gene therapy for muscle diseases.
Unified mechanistic analysis of polar reactions of diaryliodonium salts (1992)

Reactions of aryl(m-carboran-9-yl)iodonium tetrafluoroborates [aryl = phenyl, (1); 4-methoxyphenyl, (2a); 4-fluorophenyl, (2b); 3-nitrophenyl, (2c); mesityl, (2d)] with Br–, NO2–(polar reactions) and PPh3(radical reactions) have been studied. Polar reactions of 1, 2a–c with Br– and NO2– lead regiospecifically to the corresponding iodoarene and substituted m-carborane. In contrast to this, reactions of 2d, containing a bulky aryl ligand, with Br– and NO2– are not regiospecific, since they produce all four possible products: 9-iodo-m-carborane, iodomesitylene, substituted m-carborane, and substituted mesitylene. These results are rationalized in terms of a new mechanism which includes formation of a 10-I-3 hypervalent intermediate and its subsequent synchronous (cheletropic) decomposition during intramolecular rotation. The mechanism can account for some novel, known chemistry of diaryliodonium ions, including the so-called ‘ortho-effect’ and the unusual reactivity of cyclic halonium cations.
Genome sequence of adherent-invasive Escherichia coli and comparative genomic analysis with other E. coli pathotypes (2010)

Up to now, the virulence-like features associated with AIEC are detectable only phenotypically. AIEC genome sequence data will facilitate the identification of genetic determinants implicated in invasion and intracellular growth, as well as enable functional genomic studies of AIEC gene expression during health and disease.
Aqueous Humor Concentrations of Bimatoprost Free Acid, Bimatoprost and Travoprost Free Acid in Cataract Surgical Patients Administered Multiple Topical Ocular Doses of LUMIGAN ® or TRAVATAN ® (2010)

Once daily topical ocular administration of LUMIGAN or TRAVATAN for 3 weeks resulted in significant concentrations of BFA and TFA in the AH. Quantifiable levels of bimatoprost amide were also measured. Maximum concentrations of BFA (30.9 nM) and TFA (3.91 nM) in the anterior chamber are sufficient to fully activate the FP prostanoid receptors in the target cells of the ciliary muscle and trabecular meshwork. Both bimatoprost in LUMIGAN and travoprost in TRAVATAN are essentially prodrugs that are rapidly hydrolyzed to their respective free acids that induce the IOP-lowering effect observed with both drugs in vivo.
Antigenic relationships among some animal rotaviruses: virus neutralization in vitro and cross-protection in piglets (1982)

The serotype, RNA electropherotype, and cross-protection properties of rotaviruses isolated from canine, simian, porcine, and human species were compared. The bovine strain B:USA:78:1A and the canine strain C:USA:81:2 were adapted to cell culture and cloned in this study. The other viruses, i.e., simian strain S:USA:79:2, porcine Ohio State University strain P:USA:77:1, and human strain WA, were already cell culture adapted, although they were further cloned for this work. The serum neutralization test was used to classify the viruses into serotype groups. Viruses which exhibited a difference of 20-fold or greater in neutralization titer were separated into different serotype groups. In this study, four major serotype groups were found, and these groups were represented by bovine, human, porcine, and canine-simian strains. From cross-protection studies, these serotype groups were found to be significantly different. With the exception of the porcine strain, none of the viruses used as vaccines protected gnotobiotic piglets from challenge with the virulent porcine Ohio State University strain of rotavirus. Furthermore, the canine virus protected piglets from challenge with the simian virus. The RNA electropherotype confirmed that the canine and simian strains were different in eight RNA segments and eliminated the possibility that they were the same virus. From these findings, it was concluded that only viruses belonging to the same serotype group can be expected to confer cross-protection, and thus, vaccines should be made with the serotypes to which the animal is likely to be exposed.
Effect of somatostatin on skin lesions and concentrations of plasma amino acids in a patient with glucagonoma-syndrome. (1988)

A case of glucagonoma syndrome in a 58-year-old male patient who had the typical skin lesions associated with severe hypoaminoacidemia is described. The decrease in amino acids has been proposed to be causally related to the dermatosis. Furthermore, it has been shown previously that somatostatin rapidly improves skin lesions in glucagonoma patients. Therefore, plasma amino acid levels were determined before and during an infusion of somatostatin prior to surgical removal of the tumor in the tail of the pancreas. During somatostatin infusion in combination with total parenteral nutrition, 10 out of 22 amino acids were in the normal range. Thus it seems unlikely that normalization of amino acid levels is responsible for the rapid improvement in skin lesions in glucagonoma patients. On the other hand it cannot be excluded that partial normalization of amino acids contributed to the observed healing process. Nevertheless, somatostatin administered prior to surgery is a useful therapeutic regimen in these patients.