gebhart/patrepeval huggingface dataset:
Molecular mechanism for osmolyte protection of creatine kinase against guanidine denaturation (2001)

The effects of osmolytes, including dimethysulfoxide, sucrose, glycine and proline, on the unfolding and inactivation of guanidine-denatured creatine kinase were studied by observing the fluorescence emission spectra, the CD spectra and the inactivation of enzymatic activity. The results showed that low concentrations of dimethysulfoxide (< 40%), glycine (< 1.5 m), proline (< 2.5 m) and sucrose (< 1.2 m) reduced the inactivation and unfolding rate constants of creatine kinase, increased the change in transition free energy of inactivation and unfolding (Delta Delta G(u)) and stabilized its active conformation relative to the partially unfolded state with no osmolytes. In the presence of various osmolytes, the inactivation and unfolding dynamics of creatine kinase were related to the protein concentrations. These osmolytes protected creatine kinase against guanidine denaturation in a concentration-dependent manner. The ability of the osmolytes to protect creatine kinase against guanidine denaturation decreased in order from sucrose to glycine to proline. Dimethysulfoxide was considered separately. This study also suggests that osmolytes are not only energy substrates for metabolism and organic components in vivo, but also have an important physiological function for maintaining adequate rates of enzymatic catalysis and for stabilizing the protein secondary and tertiary conformations.
Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone ( GetGoal ‐P) (2013)

Lixisenatide once daily significantly improved glycaemic control with a low risk of hypoglycaemia, and was well tolerated over 24 weeks and during the long-term, double-blind extension period in patients with T2DM insufficiently controlled on pioglitazone ± metformin.
Monoallelic amplification of estrogen receptor-alpha expression in breast cancer. (2000)

Gene amplification and loss of heterozygosity are alterations to chromosomal structure whereby tumor cells alter patterns of gene expression. We have identified a novel mechanism of gene regulation in which cancer cells predominantly express one of the two alleles of a gene. Estrogen receptor (ER)-alpha is overexpressed in hormone-responsive breast cancer compared with normal breast epithelial cells. Using a polymorphism of codon 10, we examined allele-specific expression of the four different ER promoters in MCF-7 breast cancer cells and primary tumors. Monoallelic amplification of expression (MAX) for all four ER promoters was identified, resulting in an allelic preference of > 100-fold. MAX was the result of an amplification of allele copy number and a preference to transcribe the amplified allele. The effect of MAX was most significant for the promoters clustered near the 1' exon, whereas the expression from the distant H promoter mirrored template copy number. MAX of the ER gene was not found to occur in normal endometrial or breast tissue. As a novel mechanism in cancer genetics, MAX can result in functional homozygosity at a gene locus.
Posttransplantation hypertension related to calcineurin inhibitors (2000)

Calcineurin inhibitors are a mainstay of transplant immunosuppression and commonly induce hypertension. They are highly lipid soluble and penetrate vascular smooth muscle cell membranes readily. Changes in vascular tone are universally observed during administration of these agents, particularly within the kidney, leading to diminished glomerular filtration and enhanced sodium retention. Disturbances of endothelial function are prevalent in many tissues, including stimulation of endothelin and impaired nitric oxide synthesis. Multiple additional pathways produce increased vasoconstriction, leading to an increase in arterial pressure. Clinical manifestations include disturbances in circadian blood pressure patterns, left ventricular hypertrophy, and acceleration of atherosclerotic and renal injury. Rapid increases in pressure occasionally produce accelerated hypertension and microangiopathic tissue damage. Principles of therapy require recognition of hazards of changing arterial pressures during calcineurin use and preferential use of vasodilating drugs, particularly dihydropyridine calcium channel blocking agents. Attention must be paid to interactions between antihypertensive agents and calcineurin inhibitor blood levels.
Structure-function relationships among highly diverse T cells that recognize a determinant from influenza virus hemagglutinin. (1990)

We have analyzed the structural and genetic basis for T cell recognition of the complex formed between antigen and class II products of the major histocompatibility complex by performing sequence analysis of T cell receptors (TCRs) induced in response to the helper T cell site 1 of the influenza virus hemagglutinin. The results demonstrate, first, that structurally highly diverse TCRs can be utilized in recognition of the same antigen/I-Ed complex: 12 of 13 TCRs utilize unique V alpha/V beta gene segment combinations, suggesting that approximately 70 different V alpha/V beta combinations are available to BALB/c mice in response to this determinant. Second, comparison of these sequences with the ability of each hybridoma to recognize a panel of peptide analogues suggests that alpha and beta chains of these TCRs frequently determine specificity for the NH2-terminal and the COOH terminal portions, respectively, of the site 1 determinant.
Synthesis of Epothilone Analogs: Toward the Development of Potent Anticancer Drugs (2002)

Abstract : Having accomplished total syntheses of epoithilone A and B, we have been engaged in a new stage of investigation that involves development of efficient strategies for a large scale epothilone preparation and search for more potent analogues. Efficient and processable syntheses of key building blocks of 12,1 3-desoxyepothilone B (dEpoB) by catalytic asymmetric induction has been achieved. dEpoB is a potent anticancer agent, showing a highly promising therapeutic potential in the currently undergoing phase I study. The syntheses of two epothilone analogues, 15(S)-aza-12,13-desoxyepothilone B and the epimeric 15(R)-aza-12,13- -desoxyepothilone B have been accomplished. Tubulin binding and cytotoxicity profiles of these analogues have also been investigated. Another epothilone, 12,13-desoxyepothilone F (dEpoF), was synthesized and evaluated for antitumor potential. The results from an in vitro assay reveal that this new analogue is highly active against various tumor cell lines with a potency comparable to that of dEpoB. In particular, the growth of resistant tumor cells is inhibited by dEpoF at concentrations where paclitaxel (Taxol) is basically ineffective. A preliminary assessment of its in vivo activity is also promising. The new analogue, containing an additional hydroxyl group at C21, provides advantages over other epothilones in terms of water solubility and can serve as a readily functionalizable handle to produce other useful compounds for pertinent biological studies.
Macrolides for the treatment of severe respiratory illness caused by novel H1N1 swine influenza viral strains (2009)

this item has no abstract. use the links below to view the complete article
Solitons in optical communications (1983)

In this paper we have calculated the effects of loss on the propagation of soliton solutions of the nonlinear Schrodinger equation. Since we are interested in the application of these results to optical communications, it is necessary to go beyond perturbative results. This is due to the fact that propagation distances in optical fibers are significantly greater than the decay length of the energy in the pulses. Some conclusions are drawn about the application of solitons in long-distance communications.
The absorption profile and availability of a physiological subcutaneously administered dose of recombinant human growth hormone (GH) in adults with GH deficiency (1999)

A dose of 1.2 IU resulted in a mean GH concentration comparable with the mean physiological GH concentration in healthy females of comparable age, height, and BMI.
Synthesis and Characterization of a Novel Green Cobalt Corrinoid1 (1996)

Treatment of the c-monocarboxylate of cyanocobalamin with diphenylphosphoryl azide affords the c-NH2 derivative in moderate yield along with a novel green corrinoid. The latter is also obtained when the amine is treated with aqueous base. A single-crystal X-ray diffraction analysis shows that the green corrinoid lacks a c side chain and contains a C7−C8 double bond indicating that the B pyrrole ring has been aromatized.
Drugs and their molecular targets: an updated overview (2008)

About 330 targets bind approved drugs, 270 encoded by the human genome and 60 belonging to pathogenic organisms. A large number of druggable targets have been recently proposed from preclinical and first clinical data, but a huge reservoir of putative drug targets, possibly several thousands, remains to be explored. This overview considers the different types of ligands and their selectivity in the main superfamilies of drug targets, enzymes, membrane transporters and ion channels, and the various classes of membrane and nuclear receptors with their signalling pathway. Recently approved drugs such as monoclonal antibodies, tyrosine kinase and proteasome inhibitors, and major drugs under clinical studies are reviewed with their molecular target and therapeutic interest. The druggability of emerging targets is discussed, such as multidrug resistance transporters and cystic fibrosis transmembrane conductance regulator (CFTR), hyperpolarization-activated cyclic nucleotides-gated (HCN), cyclic nucleotide-gated (CNG) and transient receptor potential (TRP) ion channels, tumour necrosis factor (TNF) and receptor activator of NFkappaB (RANK) receptors, integrins, and orphan or recently deorphanized G-protein-coupled and nuclear receptors. Large advances have been made in the therapeutical use of recombinant cytokines and growth factors (i.e. tasonermin, TNFalpha-1a; becaplermin, platelet-derived growth factor (PDGF); dibotermin-alpha, bone morphogenetic proteins (BMP)2; anakinra, interleukin-1 receptor antagonist protein (IRAP), and in enzyme replacement therapy, i.e. algasidase (alpha-galactosidase) and laronidase (alpha-l-iduronidase). New receptor classes are emerging, e.g. membrane aminopeptidases, and novel concepts are stimulating drug research, e.g. epigenetic therapy, but the molecular target of some approved drugs, such as paracetamol and imidazolines, still need to be identified.
Photochemistry of ketones in solution. 72. Characterization of transient intermediates in the photochemistry of cyclohexenones (1984)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPhotochemistry of ketones in solution. 72. Characterization of transient intermediates in the photochemistry of cyclohexenonesD. I. Schuster, R. Bonneau, D. A. Dunn, J. M. Rao, and J. Joussot-DubienCite this: J. Am. Chem. Soc. 1984, 106, 9, 2706–2707Publication Date (Print):May 1, 1984Publication History Published online1 May 2002Published inissue 1 May 1984https://doi.org/10.1021/ja00321a042RIGHTS & PERMISSIONSArticle Views112Altmetric-Citations36LEARN 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 InReddit PDF (295 KB) Get e-Alerts Get e-Alerts
Seizures and Epileptiform Activity in the Early Stages of Alzheimer Disease (2013)

Common clinical features of patients with aMCI- or AD-associated epilepsy at our center included early age at onset of cognitive decline, early incidence of seizures in the disease course, unilateral temporal epileptic foci detected by serial/extended EEG, transient cognitive dysfunction, and good seizure control and tolerability with lamotrigine and levetiracetam. Careful identification and treatment of epilepsy in such patients may improve their clinical course.
HMGB1 as a DNA-binding cytokine (2002)

HMGB1 (high mobility group box chromosomal protein 1), historically known as an abundant, nonhistone architectural chromosomal protein, is extremely conserved across species. As a nuclear protein, HMGB1 stabilizes nucleosomes and allows bending of DNA that facilitates gene transcription. Unexpectedly, recent studies identified extracellular HMGB1 as a potent macrophage-activating factor, signaling via the receptor for advanced glycation end-products to induce inflammatory responses. It is released as a late mediator during inflammation and participates in the pathogenesis of systemic inflammation after the early mediator response has resolved. HMGB1 occupies a critical role as a proinflammatory mediator passively released by necrotic but not apoptotic cells. Necrotic Hmgb1(-/-) cells mediate minimal inflammatory responses. Stimulated macrophages actively secrete HMGB1 to promote inflammation and in turn, stimulate production of multiple, proinflammatory cytokines. HMGB1 mediates endotoxin lethality, acute lung injury, arthritis induction, activation of macrophages, smooth muscle cell chemotaxis, and epithelial cell barrier dysfunction. HMGB1 is structurally composed of three different domains: two homologous DNA-binding sequences entitled box A and box B and a highly, negatively charged C terminus. The B box domain contains the proinflammatory cytokine functionality of the molecule, whereas the A box region has an antagonistic, anti-inflammatory effect with therapeutic potential. Administration of highly purified, recombinant A box protein or neutralizing antibodies against HMGB1 rescued mice from lethal sepsis, even when initial treatment was delayed for 24 h after the onset of infection, establishing a clinically relevant therapeutic window that is significantly wider than for other known cytokines.
E-COMMERCE RESPONSE TIME: A REFERENCE MODEL (2000)

This paper presents a framework that describes all the components that make up the response time of an e-commerce application. Understanding this fundamental framework is the key to implementing responsive e-commerce systems. The paper discusses examples of how e-commerce application response times can be improved in three ways: by reducing the overall number of components, by speeding up individual components, and by moving some components off the synchronous response time path.
Epidermal-Growth-Factor-Dependent Transformation by a Human EGF Receptor Proto-Oncogene (1987)

The epidermal growth factor (EGF) receptor gene EGFR has been placed in a retrovirus vector to examine the growth properties of cells that experimentally overproduce a full-length EGF receptor. NIH 3T3 cells transfected with the viral DNA or infected with the corresponding rescued retrovirus developed a fully transformed phenotype in vitro that required both functional EGFR expression and the presence of EGF in the growth medium. Cells expressing 4 x 10(5) EGF receptors formed tumors in nude mice, while control cells did not. Therefore, the EGFR retrovirus, which had a titer on NIH 3T3 cells that was greater than 10(7) focus-forming units per milliliter, can efficiently transfer and express this gene, and increased numbers of EGF receptors can contribute to the transformed phenotype.
NEWTON'S METHOD FOR EQUATIONS RELATED TO EXPONENTIAL FUNCTION (2001)

For some equation related with exponential function, we seek roots and find the properties of the roots. By using the relation of the roots and attractors, we find a region in the basin of attraction of the attractor at infinity for Newton's method for solving given equation.
Maturation and enucleation of primitive erythroblasts during mouse embryogenesis is accompanied by changes in cell-surface antigen expression (2006)

Primitive erythroblasts (EryPs) are the first hematopoietic cell type to form during mammalian embryogenesis and emerge within the blood islands of the yolk sac. Large, nucleated EryPs begin to circulate around midgestation, when connections between yolk sac and embryonic vasculature mature. Two to 3 days later, small cells of the definitive erythroid lineage (EryD) begin to differentiate within the fetal liver and rapidly outnumber EryPs in the circulation. The development and maturation of EryPs remain poorly defined. Our analysis of embryonic blood at different stages reveals a stepwise developmental progression within the EryP lineage from E9.5 to E12.5. Thereafter, EryDs are also present in the bloodstream, and the 2 lineages are not easily distinguished. We have generated a transgenic mouse line in which the human epsilon-globin gene promoter drives expression of green fluorescent protein exclusively within the EryP lineage. Here, we have used this line to characterize changes in cell morphology and surface-marker expression as EryPs mature and to track EryP numbers and enucleation throughout gestation. This study identifies previously unrecognized synchronous developmental stages leading to the maturation of EryPs in the mouse embryo. Unexpectedly, we find that EryPs are a stable cell population that persists through the end of gestation.
Bacterial Contamination of the Hands of Hospital Staff During Routine Patient Care (1999)

The duration and type of patient care affect hand contamination. Furthermore, because hand antisepsis was superior to hand washing, intervention trials should explore the role of systematic hand antisepsis as a cornerstone of infection control to reduce cross-transmission in hospitals.
Immunogenicity of Bovine Herpes virus 1 Glycoprotein D in Mice: Effect of Antigen Form on the Induction of Cellular and Humoral Immune Responses (1996)

For the development of veterinary subunit vaccines, modifications to the antigen may be needed to make the production of these vaccines cost effective. To investigate the effect of antigen modifications on immune response, we used glycoprotein D, one of the major glycoproteins of bovine herpesvirus-1 (BHV-1), as a model antigen. We developed a mouse model to assess the immune response elicited by immunization with either a recombinant truncated (tgD) or the authentic full-length (gD) form of BHV-1 gD in VSA3, a novel water-in-oil adjuvant. Both forms of BHV-1 gD antigen induced good levels of cell-mediated immunity, as evaluated by antigen-specific proliferative response and cytokine (IFN-gamma and IL-4) production. Following primary immunization, the humoral immune response induced by gD was superior to that elicited by vaccination with tgD. However, after a secondary immunization, a strong and similar antibody response to BHV-1 gD was induced by both forms of the antigen. The difference in immunogenicity between gD and tgD after primary immunization was not due to the loss of immunogenic epitopes in the truncated antigen or the ability to associate with the adjuvant VSA3. Our results indicate that both gD and tgD are capable of efficiently inducing a cell-mediated immune response, and although recombinant tgD is less efficient in inducing a primary humoral immune response when compared to the full-length gD, tgD effectively primed for a secondary antibody response.
Epidermal Impedance Sensing Sheets for Precision Hydration Assessment and Spatial Mapping (2013)

This paper presents a class of hydration monitor that uses ultrathin, stretchable sheets with arrays of embedded impedance sensors for precise measurement and spatially multiplexed mapping. The devices contain miniaturized capacitive electrodes arranged in a matrix format, capable of integration with skin in a conformal, intimate manner due to the overall skin-like physical properties. These "epidermal" systems noninvasively quantify regional variations in skin hydration, at uniform or variable skin depths. Experimental results demonstrate that the devices possess excellent uniformity, with favorable precision and accuracy. Theoretical models capture the underlying physics of the measurement and enable quantitative interpretation of the experimental results. These devices are appealing for applications ranging from skin care and dermatology, to cosmetology and health/wellness monitoring, with the additional potential for combined use with other classes of sensors for comprehensive, quantitative physiological assessment via the skin.
Solution Structure and Dynamics of the CX3C Chemokine Domain of Fractalkine and Its Interaction with an N-Terminal Fragment of CX3CR1, (1999)

Fractalkine, a novel CX3C chemokine, is unusual because of both its membrane-associated structure and its direct role in cell adhesion. We have solved the solution structure of the chemokine domain of fractalkine (residues 1-76) by heteronuclear NMR methods. The 20 lowest energy structures in the ensemble have an average backbone rmsd of 0.43 A, excluding the termini. In contrast to many other chemokines which form homodimers, fractalkine's chemokine module is monomeric. Comparison of the structure to CC and CXC chemokines reveals interesting differences which are likely to be relevant to receptor binding. These include a bulge formed by the CX3C motif, the relative orientation of the N-terminus and 30's loop (residues 30-38), and the conformation of the N-loop (residues 9-19). 15N backbone relaxation experiments indicate that these same regions of the protein are dynamic. We also titrated 15N-labeled protein with a peptide from the N-terminus of the receptor CX3CR1 and confirmed that this region of the receptor contacts the fractalkine chemokine domain. Interestingly, the binding site maps roughly to the regions of greatest flexibility and structural variability. Together, these data provide a first glimpse of how fractalkine interacts with its receptor and should help guide mutagenesis studies to further elucidate the molecular details of binding and signaling through CX3CR1.
A comprehensive head pose and gaze database (2007)

Within the past decade, many computational approaches have been developed to estimate gaze directions of persons based on their facial appearance. Most researchers used common face datasets with only a l imited representation of different head poses to train and verify their algorithms. Moreover, in most datasets, faces have neither a defined gaze direction, nor do they incor porate different combinations of eye gaze and head pose. Therefore, we recorded an extended dataset of 20 sub jects including faces in various combinations of head pos e and eye gaze leading to a total amount of 2220 colour i mages (111 per subject). The images were produced under controlled conditions, i.e. we used a technique to make sure that the subjects adjust their head and eyes appropriately. Furthermore, all images are manually labelled with landmarks indicating important featur es of the face. Finally, we evaluate the dataset with two computational methods for head pose and gaze estimation respectively.