gebhart/patrepeval huggingface dataset:
The 2.1 Å Resolution Structure of Cyanopindolol-Bound β1-Adrenoceptor Identifies an Intramembrane Na+ Ion that Stabilises the Ligand-Free Receptor (2014)

The β1-adrenoceptor (β1AR) is a G protein-coupled receptor (GPCR) that is activated by the endogenous agonists adrenaline and noradrenaline. We have determined the structure of an ultra-thermostable β1AR mutant bound to the weak partial agonist cyanopindolol to 2.1 Å resolution. High-quality crystals (100 μm plates) were grown in lipidic cubic phase without the assistance of a T4 lysozyme or BRIL fusion in cytoplasmic loop 3, which is commonly employed for GPCR crystallisation. An intramembrane Na+ ion was identified co-ordinated to Asp872.50, Ser1283.39 and 3 water molecules, which is part of a more extensive network of water molecules in a cavity formed between transmembrane helices 1, 2, 3, 6 and 7. Remarkably, this water network and Na+ ion is highly conserved between β1AR and the adenosine A2A receptor (rmsd of 0.3 Å), despite an overall rmsd of 2.4 Å for all Cα atoms and only 23% amino acid identity in the transmembrane regions. The affinity of agonist binding and nanobody Nb80 binding to β1AR is unaffected by Na+ ions, but the stability of the receptor is decreased by 7.5°C in the absence of Na+. Mutation of amino acid side chains that are involved in the co-ordination of either Na+ or water molecules in the network decreases the stability of β1AR by 5-10°C. The data suggest that the intramembrane Na+ and associated water network stabilise the ligand-free state of β1AR, but still permits the receptor to form the activated state which involves the collapse of the Na+ binding pocket on agonist binding.
Expression, isolation and characterization of recombinant [Arg15,Glu52]aprotinin. (1988)

The [Arg15,Glu52]aprotinin gene has been constructed from a synthetic [Glu52]-aprotinin gene via an exchange of the appropriate DNA cassette. The gene has been fused to the N-terminal part of the bacteriophage MS-2 polymerase and expressed in a temperature inducible E. coli expression system. The produced fusion protein is deposited as inclusion bodies. Pure and functionally active [Arg15,Glu52]aprotinin has been obtained after cleavage of the purified fusion protein and renaturation of the aprotinin homologue. Recombinant [Arg15,Glu52]aprotinin shows good inhibition of human anionic and cationic trypsin (Ki less than or equal to 10(-11)M) and of human plasma kallikrein (Ki = 3.2 x 10(-10)M). The inhibition constants for human plasmin are Ki = 1.3 x 10(-10)M and for human urinary kallikrein Ki = 10(-11)M. No inhibition was found with the human proteinases thrombin, coagulation factor Xa, urokinase, tissue plasminogen activator, cathepsin G, leukocyte elastase and pancreatic elastase.
Components of the SMRT Corepressor Complex Exhibit Distinctive Interactions with the POZ Domain Oncoproteins PLZF, PLZF-RARα, and BCL-6 (1998)

Many transcription factors function by repressing gene transcription. For a variety of these transcription factors the ability to physically recruit auxiliary proteins, denoted corepressors, is crucial for the ability to silence gene expression. We and others have previously implicated the SMRT corepressor in the actions of the PLZF transcription factor and in the function of its oncogenic derivative, PLZF-retinoic acid receptor (RARalpha), in promyelocytic leukemia. We report here that PLZF, and a structurally similar transcriptional repressor, BCL-6, can interact with a variety of corepressor proteins in addition to SMRT, including the mSin3A protein and (for PLZF) histone deacetylase-1. Unexpectedly, these additional interactions with corepressor components are nonequivalent for these otherwise similar oncoproteins, suggesting that transcriptional repression by BCL-6 and by PLZF may differ in mechanism. Furthermore, we demonstrate that the oncogenic PLZF-RARalpha chimera lacks several important corepressor interaction sites that are present in the native PLZF protein. Thus the t(11;17) translocation that creates the PLZF-RARalpha chimera generates an oncoprotein with potentially novel regulatory properties distinct from those of either parental protein. Our results demonstrate that otherwise similar transcription factors can differ notably in their interactions with the corepressor machinery.
Biophysical Injury Mechanisms in Electrical Shock Trauma (2000)

Electrical shock trauma tends to produce a very complex pattern of injury, mainly because of the multiple modes of frequency-dependent tissue-field interactions. Historically, Joule heating was thought to be the only cause of electrical injuries to tissue by commercial-frequency electrical shocks. In the last 15 years, biomedical engineering research has improved the understanding of the underlying biophysical injury mechanisms. Besides thermal burns secondary to Joule heating, permeabilization of cell membranes and direct electroconformational denaturation of macromolecules such as proteins have also been identified as tissue-damage mechanisms. This review summarizes the physics of tissue injury caused by contact with commercial-frequency power lines, as well as exposure to lightning and radio frequency (RF), microwave, and ionizing radiation. In addition, we describe the anatomic patterns of the resultant tissue injury from these modes of electromagnetic exposures.
Evaluation of Recent Techniques Used to Identify Individual Strains of Saccharomyces Yeasts (1990)

Three techniques (yeast chromosome fingerprinting, DNA restriction pattern analysis, and total soluble protein profiling) were compared for their abilities to differentiate strains of bakers' and brewers' yeasts. While all three methods were able to distinguish between species of Saccharomyces (ale vs. lager yeasts), only chromosome fingerprinting was routinely able to differentiate strains within the same species. On the basis of these results, chromosome fingerprinting is proposed as the method of choice to differentiate industrial strains of Saccharomyces yeasts.
Phase I and pharmacokinetic studies of high-dose uridine intended for rescue from 5-fluorouracil toxicity. (1984)

The clinical effects and pharmacokinetics of high-dose uridine were determined in seven patients with advanced-stage cancer and in one healthy volunteer. Uridine was also examined for its effect on 5-fluorouracil toxicity in two patients. Uridine was administered as a 1-hr i.v. infusion at doses of 1 to 12 g/sq m. Plasma and urine samples were analyzed for uridine and uracil using high-pressure liquid chromatography. In 23 courses of uridine alone, the only toxicity observed was transient shivering after one of two courses at 12 g/sq m. This side effect was also seen after administration of uridine (10 g/sq m) during combination with 5-fluorouracil. The pretreatment plasma uridine concentration was elevated from low micromolar to millimolar levels with uridine administration at doses up to 12 g/sq m. Maximal areas under the concentration-time curve were about 5 mmol/liter/hr. Both peak plasma level and area under the curve for uridine increased linearly with dose. Uridine plasma decay curves were biphasic with a terminal half-life of 118 min. Half-life, volume of distribution (634 ml/kg), and total clearance (4.98 ml/kg/min) appeared to be independent of dose. Plasma uracil concentration increased gradually after administration of uridine to plateau levels. Maximal plasma uracil concentrations were about one-tenth that of peak uridine concentrations. The plasma uracil level declined with a half-life of about 40 min after uridine levels decreased to 300 microM. Total urinary excretion of uridine was 24% of the dose, while the amount of uracil recovered in urine was 3.4%. In two patients, uridine rescue was attempted during 5-fluorouracil dose escalation. Uridine at 5 to 6 g/sq m given on 1 or on 2 days after 5-fluorouracil did not prevent myelosuppression and gastrointestinal toxicity associated with increasing plasma concentrations of 5-fluorouracil. These data show that uridine administered as a 1-hr infusion at doses which provide peak plasma uridine concentrations in the millimolar range is well tolerated. Rapid elimination of uridine primarily due to catabolism results in modest exposure to substantially elevated plasma uridine concentrations. Preliminary findings suggest that prolonged treatment with uridine may be required to test its potential to rescue patients from 5-fluorouracil toxicity.
Design, preparation and properties of novel flame retardant thermosetting vinyl ester copolymers based on castor oil and industrial dipentene (2017)

Abstract A novel bio-based flame-retardant thermosetting vinyl ester resin monomer was synthesized from castor oil. The chemical structures of the monomer was characterized by FTIR and 1H-NMR. In order to improve its rigidity and expand its application in the field of bio-based materials, it was mixed with certain proportions of another reactive bio-based VER monomer, which had rigid and strong polar groups, and then a series of copolymers were prepared with thermal curing method. Then their tensile property, hardness, morphology of fractured surface, flame retardant property, DMA and thermostability were all investigated. The results indicated that the copolymers had relatively high tensile strength of 11.2 MPa, and the limiting oxygen index is above 23% in all prepared copolymers. DMA demonstrates that the glass transition temperature of the cured resins is up to 56.1°C. Thermogravimetric analysis shows that the copolymers have excellent thermal stability.
Imaging and quantifying transverse flow velocity with the Doppler bandwidth in a phase-resolved functional optical coherence tomography (2002)

The Doppler bandwidth extracted from the standard deviation of the frequency shift in phase-resolved functional optical coherence tomography (F-OCT) was used to image the velocity component that is transverse to the optical probing beam. It was found that above a certain threshold level the Doppler bandwidth is a linear function of flow velocity and that the effective numerical aperture of the optical objective in the sample arm determines the slope of this dependence. The Doppler bandwidth permits accurate measurement of flow velocity without the need for precise determination of flow direction when the Doppler flow angle is within +/-15 degrees perpendicular to the probing beam. Such an approach extends the dynamic range of flow velocity measurements obtained with the phase-resolved F-OCT.
An E and C modification of the .beta.-.pi. solvation approach (1982)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAn E and C modification of the .beta.-.pi. solvation approachPeter E. Doan and Russell S. DragoCite this: J. Am. Chem. Soc. 1982, 104, 17, 4524–4529Publication Date (Print):August 1, 1982Publication History Published online1 May 2002Published inissue 1 August 1982https://pubs.acs.org/doi/10.1021/ja00381a004https://doi.org/10.1021/ja00381a004research-articleACS PublicationsRequest reuse permissionsArticle Views60Altmetric-Citations15LEARN 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
Influence of homocysteine on fibrin network lysis (2006)

To elucidate some of the links between homocysteine and vascular disease, we have evaluated the effect of the amino acid on the formation (by kinetics studies), structure (by electron microscopy) and lysis of the fibrin network, using tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). We have studied whether homocysteine could alter the activity of the components involved in fibrinolysis (by amidolytic and thrombolytic methods). The results showed that homocysteine-associated networks were more compact and branched than controls (52 +/- 6 vs 44 +/- 5 fibers/field, P = 0.008), and were formed by shorter and thicker fibers. This clot proved to be more resistant to fibrinolysis with u-PA than control [lysis time 50%: 257 +/- 16 (homocysteine) vs 187 +/- 6 min (control); P < 0.004], but there were no differences with t-PA. Homocysteine did not affect the biological activities of plasmin, or plasminogen activation by t-PA and u-PA. Defective fibrinolysis with u-PA was therefore associated with homocysteine-fibrin structural alterations rather than the homocysteine effect on the biological activities of the fibrinolytic components evaluated. Results suggest that hyperhomocysteinemic patients could produce tight clots, were more resistant to lysis, and generated a procoagulant environment in situ. We believe that our findings may contribute to understanding the mechanisms involved in the homocysteine harmful effect.
Molecular pathology of filamin A: diverse phenotypes, many functions (2004)

Defective cell signalling during embryonic development is a well-recognized modus operandi of mutations in genes that lead to congenital malformations. This signalling occurs within and around a dynamic cellular cytoskeleton that is continuously under modulating influences during morphogenesis. Evidence is accumulating to suggest that filamin A, an actin-binding protein and the product of one of three paralogous filamin genes in humans, represents a key molecule that connects such signalling events to modulation of the cellular cytoskeletal architecture. This review summarizes the clinical consequences of mutations in the gene encoding filamin A, FLNA. The molecular pathology of this gene suggests remarkable functional pleiotropy, indicative of diverse roles in embryonic, fetal and postnatal development.
Labeled aryl fluorides from the nucleophilic displacement of activated nitro groups by 18F‐F− (1983)

Abstract Nucleophilic displacement of activated nitro groups by 18 F‐fluoride ion is an efficient route to fluorine‐18 labeled aromatics, which can be obtained in the no‐carrier‐added state if required. The basic features of the fluorodenitration process are comparatively evaluated, and the influence of the experimental variables on its course are discussed. Examples concerning the preparation of typical 18 F‐labeled aromatic molecules are reported.
Fetal Hemoglobin in Sickle Cell Anemia: Determinants of Response to Hydroxyurea (1997)

Hydroxyurea (HU) can increase fetal hemoglobin (HbF) in sickle cell anemia (HbSS). To identify determinants of the HbF response, we studied 150 HU-treated patients grouped by quartiles of change in HbF from baseline to 2 years. Half of the HU-assigned patients had long-term increments in HbF. In the top two quartiles, HbF increased to 18.1% and 8.8%. These patients had the highest baseline neutrophil and reticulocyte counts, and largest treatment-associated decrements in these counts. In the lower two quartiles, 2-year HbF levels (4.2% and 3.9%) and blood counts changed little from baseline. In the highest HbF response quartile, myelosuppression developed in less than 6 months, compliance was best, and final doses of HU were 15 to 22.5 mg/kg. All four quartiles had substantial increases of F cells in the first year. This was maintained for 2 years only in the top three quartiles. Leukocyte and reticulocyte counts decreased initially in all quartiles, but drifted back toward baseline levels in the lowest HbF response quartile. Initial HbF level and phenotype of the F-cell production (FCP) locus were not associated with HbF response, but absence of a Central African Republic (CAR) haplotype was. Bone marrow ability to withstand HU treatment may be important for sustained HbF increases during HU treatment of HbSS.
p125Fak Focal Adhesion Kinase Is a Substrate for the Insulin and Insulin-like Growth Factor-I Tyrosine Kinase Receptors (1998)

The focal adhesion kinase p125(Fak) is a widely expressed cytosolic tyrosine kinase, which is involved in integrin signaling and in signal transduction of a number of growth factors. In contrast to tyrosine kinase receptors such as the platelet-derived growth factor and the hepatocyte growth factor receptors, which induce p125(Fak) phosphorylation, insulin has been shown to promote its dephosphorylation. In this study, we compared p125(Fak) phosphorylation in insulin-stimulated cells maintained in suspension or in an adhesion state. We found that, in nonattached cells, insulin promotes p125(Fak) phosphorylation, whereas dephosphorylation occurred in attached cells. This was observed in Rat-1 fibroblasts overexpressing the insulin receptor, as well as in Hep G2 hepatocytes and in 3T3-L1 adipocytes expressing more natural levels of insulin receptors. Insulin-induced p125(Fak) phosphorylation correlated with an increase in paxillin phosphorylation, indicating that p125(Fak) kinase activity may be stimulated by insulin. Mixing of purified insulin or insulin-like growth factor-I (IGF-I) receptors with p125(Fak) resulted in an increase in p125(Fak) phosphorylation. Using a kinase-deficient p125(Fak) mutant, we found that this protein is a direct substrate of the insulin and IGF-I receptor tyrosine kinases. This view is supported by two additional findings. (i) A peptide corresponding to p125(Fak) sequence comprising amino acids 568-582, which contains tyrosines 576 and 577 of the kinase domain regulatory loop, is phosphorylated by the insulin receptor; and (ii) p125(Fak) phosphorylation by the insulin receptor is prevented by addition of this peptide. Finally, we observed that p125(Fak) phosphorylation by the receptor results in its activation. Our results show that the nature of the cross-talk between the insulin/IGF-I receptors and p125(Fak) is dependent on the cell architecture, and hence the interaction of the insulin/IGF-I signaling system with the integrin system will vary accordingly.
Porcine circovirus antigens in PK-15 cell line (ATCC CCL-33) and evidence of antibodies to circovirus in Canadian pigs. (1989)

Permanent infection of a PK-15 (ATCC CCL-33) cell line by the porcine circovirus was demonstrated. This virus appears to be common in the Canadian swine population as indicated by the presence of antibodies detected by indirect immunofluorescence or immunoperoxidase tests in the serum of culled sows and sows in commercial herds. One source of the PK-15 cell line was found to be free of circovirus antigen.
IP exchange systems-Redefining distributed communications in the enterprise (2002)

The IP Exchange systems, which include IP ExchangeComm† and IP ExchangeLink†, are Internet protocol (IP) private branch exchanges (PBXs) designed and developed by Lucent Technologies. They are implemented using an advanced distributed computing architecture that leverages open computing and communications standards to create a scalable, reliable switching and feature service platform. This paper introduces the IP Exchange systems and presents their technical approach, their innovative architecture, and the benefits of that architecture.
Quantitative Assessment of the Spatial Organization of Atrial Fibrillation in the Intact Human Heart (1996)

Using a novel method to measure the spatial organization of atrial activation during AF, we have demonstrated that AF in the intact human heart is organized over a length scale consistent with reentrant excitation. Preliminary results suggest a relationship between measured spatial organization and the clinical course of the arrhythmia. Further work is needed to determine whether measurement of spatial organization may be useful in prospective patient-specific selection of therapeutic options.
Genetic mapping of the lytA and lytB loci of Escherichia coli, which are involved in penicillin tolerance and control of the stringent response (1992)

The mutations in nine independently isolated temperature-sensitive mutants of Escherichia coli, which exhibited penicillin tolerance and induction of the stringent response at the restrictive temperature, were assigned to two new loci designated lytA (7 alleles) and lytB (2 alleles) at 58 and 0.4 min on the linkage map, respectively. Key words: bacteriolysis, penicillin tolerance, stringent response.
Bottomhole system works over, completes horizontal wells (1990)

As the number of horizontal wells increases, it has become more apparent that a reliable completion/workover system for horizontal wells is required. The authors' company, a specialist in cased-hole workovers, successfully tested a new bottomhole system which provides a reliable means for conducting horizontal well completions and workovers. The authors present a field test carried out in a horizontal well. The milling operation was successfully completed in 2.5 days with a minimum number of bottomhole assemblies. The bottomhole assembly used to conduct this milling operation is shown. This assembly consists of five components.
Comparison of two-dimensional and three-dimensional models for profile simulation of poly-Si etching of finite length trenches (1998)

The development of two-dimensional (2D) profile simulators for fabrication of microelectronics features has significantly progressed during the past few years and now enables modeling of etch profile evolution for many different plasma processing conditions. Increasingly complex devices which have three-dimensional (3D) (that is, asymmetric) structures are now being designed. These structures require improved dimensionality in profile simulators to capture their most important features. Under many conditions, such as circular via etching, two-dimensional profile simulators can be used to address 3D structures. A legitimate issue is to what degree these 2D approaches can indeed be applied to truly 3D structures. In this article, we present results from a 3D profile simulator for the purpose of comparing profiles for innately 3D features to results obtained from a 2D profile simulation. It has been found that profiles obtained from the 3D simulators exhibit greater sidewall sloping in three-plane corners than predicted by the 2D simulator. The implication to process design is that a greater degree of overetching will be required to clear these corners than predicted by the 2D simulators. Asymmetries as well as the angular spread of the ion flux distribution are examined to determine their role in 3D profile evolution.
Investigation of the Effect of Temperature and Pressure on Wettability Using Modified Pendant Drop Method (1995)

Abstract Wettability is a key parameter that affects the petrophysical properties of reservoir rocks. The objective of the present work is to investigate the influence of temperature and pressure on the wettability of reservoir rocks. An experimental method for the measurements of contact angle at elevated temperature and pressure has been developed, in which a Pendant Drop Interfacial Tension Cell was modified. Experimental results of contact angle and interfacial tension for two different crude oil-brine-quartz/calcite and mineral oil-distilled water systems over a range of temperatures and pressures are reported. Contact angle for the systems studied increased with pressure, increased with temperature for sandstone system and decreased with temperature for carbonate system.