gebhart/patrepeval huggingface dataset:
Mechanisms of Thrombin Receptor Agonist Specificity (1995)

Identification of the docking interactions by which peptide agonists activate their receptors is critical for understanding signal transduction at the molecular level. The human and Xenopus thrombin receptors respond selectively to their respective hexapeptide agonists, SFLLRN and TFRIFD. A systematic analysis of human/Xenopus thrombin receptor chimeras revealed that just two human-for-Xenopus amino acid substitutions, Phe for Asn87 in the Xenopus receptor's amino-terminal exodomain and Glu for Leu260 in the second extracellular loop, conferred human receptor-like specificity to the Xenopus receptor. This observation prompted complementation studies to test the possibility that Arg5a in the human agonist peptide might normally interact with Glu260 in the human receptor. The mutant agonist peptide SFLLEN was a poor agonist at the wild type human receptor but an effective agonist at a mutant human receptor in which Glu260 was converted to Arg. An "arginine scan" of the receptor's extracellular surface revealed additional complementary mutations in the vicinity of position 260 and weak complementation at position 87 but not elsewhere in the receptor. Strikingly, a double alanine substitution that removed negative charge from the Glu260 region of the human receptor also effectively complemented the SFLLEN agonist. The functional complementation achieved with single Arg substitutions was thus due at least in part to neutralization of a negatively charged surface on the receptor and not necessarily to introduction of a new salt bridge. By contrast, charge neutralization did not account for the gain of responsiveness to SFLLRN seen in the human/Xenopus receptor chimeras. Thus two independent approaches, chimeric receptors and arginine scanning for complementary mutations, identified the Glu260 region and to a lesser degree Phe87 as important determinants of agonist specificity. These extracellular sites promote receptor responsiveness to the "correct" agonist and inhibit responsiveness to an "incorrect" agonist. They may participate directly in agonist binding or regulate agonist access to a nearby docking site.
Evaluation of GRAMM low-resolution docking methodology on the hemagglutinin-antibody complex (1997)

A single protein-protein pair, the complex of the influenza virus hemagglutinin with an antibody (Fab BH151), was suggested for prediction at the second experiment on the Critical Assessment of Techniques for Protein Structure Prediction. To predict the structure of the complex, we applied our docking program GRAMM at a decreased resolution (to accommodate the conformational inaccuracies). The lowest-energy match showed a remarkable "low-resolution" surface complementarity between the molecular structures. After receiving the experimental structure of the complex we had a chance to verify our assumptions and results. The analysis of the hemagglutinin-antibody interface revealed several significant conformational changes in the side chains, which resulted in deep interpenetrations of the hemagglutinin and the antibody structures. This confirmed our initial assumption that the structural changes will be beyond the tolerance of high-resolution rigid-body docking. The comparison of the predicted low-resolution match, submitted as the solution, and the experimentally determined complex showed significant structural discrepancies in the orientation of the antibody, due to the low-resolution character of the docking. Because of the severe structural errors, no residue-residue contacts were predicted correctly. However, a significant part of the antigenic site was determined. This illustrates the practical value of the present methodology for the initial prediction of the binding site, as well as points out the problem of transition from the low-resolution predictions of protein-protein complexes to the accurate structure.
InitialH2O-induced Oxidation of Si(100)–(2×1) (1997)

Surface infrared absorption spectroscopy and density functional cluster calculations are used to definitively demonstrate that the Si-Si dimer bond is the target for the initial insertion of oxygen into the Si(100)-- $(2\ifmmode\times\else\texttimes\fi{}1)$ surface, following ${\mathrm{H}}_{2}\mathrm{O}$ exposure and annealing. This reaction, in turn, facilitates the subsequent incorporation of O into the Si backbonds, thereby promoting (local) oxidation.
Evaluation of Kromoscopy: resolution of glucose and urea (2000)

Kromoscopy involves the transmission of a broad band of electromagnetic radiation through the sample of interest. The transmitted light is collected and divided evenly into four detector channels with complementary bandpass functions. This optical configuration provides high signal-to-noise ratios that are ideal for analytical measurements. The molecular basis of the four-channel response is critical, because it directly influences selectivity of the measurement and, therefore, the feasibility of applications in complex sample matrices. Selectivity of the Kromoscopic signal is demonstrated by resolution of glucose and urea with four channels of information collected over the 800-1300-nm near-infrared spectral region. Analysis of the individual channel responses indicates that the displacement of water from the optical path by the dissolution of solute is a major component of the Kromoscopic measurement in this spectral region. Nevertheless, significant differences are observed in channel responses for glucose and urea. A three-dimensional vector plot of the data highlights these differences and reveals unique vector directions for glucose and urea. This difference in direction of the response vectors represents the principal basis for distinguishing glucose and urea dissolved in aqueous solutions.
Morbidity, Mortality, and Healthcare Burden of Nosocomial Clostridium Difficile -Associated Diarrhea in Canadian Hospitals (2002)

N-CDAD is a common and serious nosocomial infectious complication in Canada, is associated with substantial morbidity and mortality, and imposes an important financial burden on healthcare institutions.
Efficacy of Duloxetine on Cognition, Depression, and Pain in Elderly Patients With Major Depressive Disorder: An 8-Week, Double-Blind, Placebo-Controlled Trial (2007)

Objective: This study compared the effects of duloxetine, 60 mg/day, versus placebo on cognition, depression, and pain in elderly patients with recurrent major depressive disorder. Method: Patients were randomly assigned (2:1) to duloxetine, 60 mg/day (N=207), or placebo (N=104) for 8 weeks in a double-blind study. The primary outcome measure was a prespecified composite cognitive score composed of four individual tests. Secondary measures included the Geriatric Depression Scale, the Hamilton Depression Rating Scale, the Visual Analogue Scale assessing pain, and standard safety and tolerability assessments. Results: Patients had a median age of 72 years (range=65–90). Duloxetine demonstrated significantly greater improvement in the composite cognitive score versus placebo (least-squares mean change from baseline to endpoint: 1.95 versus 0.76), driven by improved verbal learning and memory. Duloxetine treatment showed significantly greater baseline-to-endpoint reductions in both Hamilton depression scale (–6.49 versus –3.72) and Geriatric Depression Scale (–4.07 versus –1.34) total scores compared with placebo. Hamilton depression scale response (37.3% versus 18.6%) and remission (27.4% versus 14.7%) rates at endpoint were significantly higher for duloxetine than for placebo. Duloxetine significantly improved Visual Analogue Scale scores for back pain and time in pain while awake versus placebo. Significantly fewer patients receiving duloxetine withdrew from the study because of lack of efficacy (2.9% versus 9.6%); the incidences of discontinuation due to adverse events were similar for duloxetine and placebo (9.7% versus 8.7%). Conclusions: Duloxetine improved cognition, depression, and some pain measures and was safe and well tolerated in elderly patients with recurrent major depressive disorder.
New Ni/sub 5/Al/sub 3/ underlayer for longitudinal magnetic recording media (2002)

We describe a new Ni/sub 5/Al/sub 3/ underlayer for high-density longitudinal magnetic recording. The Ni/sub 5/Al/sub 3/ underlayer has the FCC derivative Ga/sub 3/Pt/sub 5/ structure. The Ni/sub 5/Al/sub 3/ [221] plane has good lattice match with the CoCrPt (101~0) plane. In addition, unlike the NiAl [112] plane, the Ni/sub 5/Al/sub 3/ [221] plane has the lowest surface energy. Hence, the Ni/sub 5/Al/sub 3/ thin film has a strong [221] texture and can induce CoCrPt (101~0) texture. The microstructure and magnetic properties of the CoCrPt-Ni/sub 5/Al/sub 3/ thin films are reported and discussed.
Long short term memory neural network for keyboard gesture decoding (2015)

Gesture typing is an efficient input method for phones and tablets using continuous traces created by a pointed object (e.g., finger or stylus). Translating such continuous gestures into textual input is a challenging task as gesture inputs exhibit many features found in speech and handwriting such as high variability, co-articulation and elision. In this work, we address these challenges with a hybrid approach, combining a variant of recurrent networks, namely Long Short Term Memories [1] with conventional Finite State Transducer decoding [2]. Results using our approach show considerable improvement relative to a baseline shape-matching-based system, amounting to 4% and 22% absolute improvement respectively for small and large lexicon decoding on real datasets and 2% on a synthetic large scale dataset.
Enteropathogenic Escherichia coli infection: history and clinical aspects (2002)

Diarrhoeagenic Escherichia coli remains an important cause of diarrhoeal disease worldwide. In terms of global public health, enteropathogenic E. coli (EPEC) and enterotoxigenic E. coli are the most important. However, enterohaemorrhagic E. coli has emerged as a cause of disease in developed countries in recent years, and a number of large outbreaks have been reported. Therefore, the importance of research into diarrhoeagenic E. coli remains an important issue. EPEC is the most widespread of the diarrhoeagenic E. coli and provides a good virulence model for other E. coli infections, as well as other pathogenic bacteria. Although the virulence mechanisms of E. coli are now better understood, there remains much to be learned before effective treatments can be developed. Type III secretion mechanisms, the locus of enterocyte effacement and various toxins are all involved in the pathogenesis of the various diarrhoeagenic E. coli and may provide targets for future therapies. This review aims to provide an update on the worldwide problem of diarrhoeagenic E. coli by focusing on EPEC, and describes the history of the organism, its incidence and the clinical aspects of infection.
Gene therapy with HSP72 is neuroprotective in rat models of stroke and epilepsy (1998)

Brain areas damaged by stroke and seizures express high levels of the 72-kd heat shock protein (HSP72). Whether HSP72 represents merely a marker of stress or plays a role in improving neuron survival in these cases has been debated. Some induced tolerance experiments have provided correlative evidence for a neuroprotective effect, and others have documented neuroprotection in the absence of HSP72 synthesis. We report that gene transfer therapy with defective herpes simplex virus vectors overexpressing hsp72 improves neuron survival against focal cerebral ischemia and systemic kainic acid administration. HSP72 overexpression improved striatal neuron survival from 62.3 to 95.4% in rats subjected to 1 hour of middle cerebral artery occlusion, and improved survival of hippocampal dentate gyrus neurons after systemic kainic acid administration, from 21.9 to 64.4%. We conclude that HSP72 may participate in processes that enhance neuron survival during transient focal cerebral ischemia and excitotoxin-induced seizures.
Preservation of ganglion cell layer neurons in age-related macular degeneration. (2001)

Interventions targeted at the outer retina early in the progression of neovascular disease should benefit from the full age-appropriate complement of GCL neurons.
Cardiac ablation via electroporation (2009)

Thermal-based ablation for the treatment of arrhythmias is known to cause issues (e.g. heat loss due to blood perfusion, mechanical damage of the tissue from excessive heat, etc.) that hamper the success of the treatment. A novel technique termed "electroporation" is a process that leads to pore formation in cell membranes. These pores may cause cellular death without inducing negative thermal effects. We successfully developed a system, tools, and methodology to operate this new ablation technique. Preliminary in vivo acute animal studies (ovine) suggest distinct lesion morphology. High transmurality success rates also suggest the possibility of applying this new ablation modality to cardiac ablation. A long term study confirming lesion durability is necessary to warrant the successful adoption of this technique.
Proliferation kinetics of plasma cells and of normal haemopoietic cells in multiple myeloma (1987)

DNA synthesis time (Ts) and 3H thymidine (TdR) labelling index (LI) of bone marrow (BM) myelomatous plasma cells (PC) and of the residual haemopoietic cell population (RHCP) were measured by in vitro quantitative 14C-TdR autoradiography in five patients with multiple myeloma (MM) in different phases of disease (three at presentation and two at relapse) and in one patient with solitary extra-osseous myeloma. One other patient with plasma cell leukaemia (PCL) was studied during an initial relapse phase and later during the leukaemic terminal phase. PC Ts was 18.8 +/- 3.7 (from 13.3 to 25.0) hr and PC LI was 2.5 +/- 1.8% (from 1.0 to 6.3%). In the case of PCL, circulating PC had a Ts of 14.4 hr and a LI of 3.1. From these experimental measurements, the fractional turnover rate (FTR-percentage of cells produced per unit time) and the potential doubling time (Td) of BMPC were calculated assuming that all BMPC were in a steady-state at the time of the study. BMPC FTR was 3.53 +/- 2.3% cells per day (from 1.2 to 6.72) and BMPC Td was 46.8 +/- 27.5 days (from 15.0 to 75.4). Comparison with results obtained in BM blasts of children with acute lymphoblastic leukaemia (ALL) indicated that BMPC had a lower proliferative activity (P less than 0.001), although BMPC Ts was not significantly different. In two patients a tumour doubling time of 6 and 13 months was determined by clinical follow up. Comparison of this parameter with Td showed a cell loss factor of more than 90% in both patients. Kinetic data relative to RHCP showed slight variations with respect to those found in normal subjects, with a general tendency towards a prolongation of Ts and a reduction of LI.
Functional Analysis of Genes for Biosynthesis of Pyocyanin and Phenazine-1-Carboxamide from Pseudomonas aeruginosa PAO1 (2001)

Two seven-gene phenazine biosynthetic loci were cloned from Pseudomonas aeruginosa PAO1. The operons, designated phzA1B1C1D1E1F1G1 and phzA2B2C2D2E2F2G2, are homologous to previously studied phenazine biosynthetic operons from Pseudomonas fluorescens and Pseudomonas aureofaciens. Functional studies of phenazine-nonproducing strains of fluorescent pseudomonads indicated that each of the biosynthetic operons from P. aeruginosa is sufficient for production of a single compound, phenazine-1-carboxylic acid (PCA). Subsequent conversion of PCA to pyocyanin is mediated in P. aeruginosa by two novel phenazine-modifying genes, phzM and phzS, which encode putative phenazine-specific methyltransferase and flavin-containing monooxygenase, respectively. Expression of phzS alone in Escherichia coli or in enzymes, pyocyanin-nonproducing P. fluorescens resulted in conversion of PCA to 1-hydroxyphenazine. P. aeruginosa with insertionally inactivated phzM or phzS developed pyocyanin-deficient phenotypes. A third phenazine-modifying gene, phzH, which has a homologue in Pseudomonas chlororaphis, also was identified and was shown to control synthesis of phenazine-1-carboxamide from PCA in P. aeruginosa PAO1. Our results suggest that there is a complex pyocyanin biosynthetic pathway in P. aeruginosa consisting of two core loci responsible for synthesis of PCA and three additional genes encoding unique enzymes involved in the conversion of PCA to pyocyanin, 1-hydroxyphenazine, and phenazine-1-carboxamide.
Weights for commutators of oscillatory type integral operators (2015)

This paper devote to set up some weighted estimates for commutators(with symbol depending on the related weights)formed by one kind of oscillatory integral operators and weighted BMO functions.
Massive evolution of the immunoglobulin heavy chain locus in children with B precursor acute lymphoblastic leukemia (2012)

The ability to distinguish clonal B-cell populations based on the sequence of their rearranged immunoglobulin heavy chain (IgH) locus is an important tool for diagnosing B-cell neoplasms and monitoring treatment response. Leukemic precursor B cells may continue to undergo recombination of the IgH gene after malignant transformation; however, the magnitude of evolution at the IgH locus is currently unknown. We used next-generation sequencing to characterize the repertoire of IgH sequences in diagnostic samples of 51 children with B precursor acute lymphoblastic leukemia (B-ALL). We identified clonal IgH rearrangements in 43 of 51 (84%) cases and found that the number of evolved IgH sequences per patient ranged dramatically from 0 to 4024. We demonstrate that the evolved IgH sequences are not the result of amplification artifacts and are unique to leukemic precursor B cells. In addition, the evolution often follows an allelic exclusion pattern, where only 1 of 2 rearranged IgH loci exhibit ongoing recombination. Thus, precursor B-cell leukemias maintain evolution at the IgH locus at levels that were previously underappreciated. This finding sheds light on the mechanisms associated with leukemic clonal evolution and may fundamentally change approaches for monitoring minimal residual disease burden.
ErbB4 and its Isoforms: Patentable Drug Targets? (2008)

Research on ErbB receptors has spearheaded the rational cancer drug design, and ErbB1 (also known as EGFR) and ErbB2 are among the first clinically validated targeted therapies. Despite the fact that applicability of ErbB4 as a drug target is still uncertain, several patents involving utilization of ErbB4 have recently been issued. Manipulation of functions of ErbB4 may be therapeutically beneficial in cancer but also in psychiatric and cardiovascular disorders. In addition, analyzing expression or mutations of ErbB4 may provide prognostic or predictive value. Contents of ErbB4-related patents, as well as biology of ErbB4 and its alternatively spliced isoforms, will be reviewed in this article.
Orphan G Protein-coupled Receptor GPR56 Regulates Neural Progenitor Cell Migration via a Gα12/13 and Rho Pathway (2008)

In the developing forebrain, the migration and positioning of neural progenitor cells (NPCs) are regulated coordinately by various molecules. Mutation of these molecules, therefore, causes cortical malformation. GPR56 has been reported as a cortical malformation-related gene that is mutated in patients with bilateral frontoparietal polymicrogyria. GPR56 encodes an orphan G protein-coupled receptor, and its mutations reduce the cell surface expression. It has also been reported that the expression level of GPR56 is involved in cancer cell adhesion and metastasis. However, it remains to be clarified how GPR56 functions in brain development and which signaling pathways are activated by GPR56. In this study, we showed that GPR56 is highly expressed in NPCs and has the ability to inhibit NPC migration. We found that GPR56 coupled with Galpha(12/13) and induced Rho-dependent activation of the transcription mediated through a serum-responsive element and NF-kappaB-responsive element and actin fiber reorganization. The transcriptional activation and actin reorganization were inhibited by an RGS domain of the p115 Rho-specific guanine nucleotide exchange factor (p115 RhoGEF RGS) and dominant negative form of Rho. Moreover, we have demonstrated that a functional anti-GPR56 antibody, which has an agonistic activity, inhibited NPC migration. This inhibition was attenuated by p115 RhoGEF RGS, C3 exoenzyme, and GPR56 knockdown. These results indicate that GPR56 participates in the regulation of NPC movement through the Galpha(12/13) and Rho signaling pathway, suggesting its important role in the development of the central nervous system.
Transactivation of the cytomegalovirus ICP36 gene promoter requires the alpha gene product TRS1 in addition to IE1 and IE2 (1992)

Very little is known about the human cytomegalovirus functions that activate gamma (late) gene expression. We have investigated the regulation of the human cytomegalovirus gamma gene encoding the ICP36 major late DNA-binding protein family (UL44). Transactivation of the ICP36 gene promoter was found to be absolutely dependent on the trs1 gene product when expressed in cells in conjunction with ie1 and ie2 gene products. Transactivation occurred poorly or not at all when any one of these three transactivators was omitted. TRS1 is a member of the US22 family of proteins and is encoded by a region near the L-S junction of the viral genome within the c repeat and adjacent Us sequences. TRS1 is highly homologous to IRS1, which is encoded from the other copy of the c repeat, and plasmid constructs carrying the irs1 gene were also able to mediate transactivation of the ICP36 promoter. RNA blot analysis of steady-rate RNA throughout infection showed that the trs1 transcript was expressed with the kinetics of an alpha gene but its accumulation was delayed relative to that of ie1 and ie2 transcripts. On the basis of these experiments, TRS1 and IRS1 are proposed to be important intermediaries in the cascade of cytomegalovirus gene expression.
Stearic acid-rich interesterified fat and trans-rich fat raise the LDL/HDL ratio and plasma glucose relative to palm olein in humans. (2007)

Both PHSO and IE fats altered the metabolism of lipoproteins and glucose relative to an unmodified saturated fat when fed to humans under identical circumstances.
How the bacterial plant pathogen Xanthomonas campestris pv. vesicatoria conquers the host (2000)

Abstract Xanthomonas campestris pv. vesicatoria (Xcv) is the causal agent of bacterial spot disease on pepper and tomato. Pathogenicity on susceptible plants and the induction of the hypersensitive reaction (HR) on resistant plants requires a number of genes, designated hrp, most of which are clustered in a 23-kb chromosomal region. Nine hrp genes encode components of a type III protein secretion apparatus that is conserved in Gram-negative plant and animal pathogenic bacteria. We have recently demonstrated that Xcv secretes proteins into the culture medium in a hrp-dependent manner. Substrates of the Hrp secretion machinery are pathogenicity factors and avirulence proteins, e.g. AvrBs3. The AvrBs3 protein governs recognition, i.e. HR induction, when bacteria infect pepper plants carrying the corresponding resistance gene Bs3. Intriguingly, the AvrBs3 protein contains eukaryotic signatures such as nuclear localization signals (NLS), and has been shown to act inside the plant cell. We postulate that AvrBs3 is transferred into the plant cell via the Hrp type III pathway and that recognition of AvrBs3 takes place in the plant cell nucleus.
Clinical Significance of the Genetic Landscape of Pancreatic Cancer and Implications for Identification of Potential Long-term Survivors (2012)

Determinations of the status of the 4 major driver genes in pancreatic cancer, and specifically the extent to which they are coexistent in an individual patients cancer, provides distinct information regarding disease progression and survival that is independent of clinical stage and treatment status.