gebhart/patrepeval huggingface dataset:
Attenuation of pulmonary hypertension secondary to left ventricular dysfunction in the rat by Rho‐kinase inhibitor fasudil (2010)

Pulmonary hypertension (PH) in left ventricular dysfunction is attributable not only to backward failure of the left ventricle, but also to increased pulmonary vascular resistance (PVR) in some patients. Recently, Rho-kinase has been known as a potent growth stimulator and mediator of vasoconstriction, and Rho-kinase inhibitors could ameliorate PVR, little is known about the role of Rho-kinase in left ventricular dysfunction-induced PH. We utilized the ascending aortic-banded rat and assessed the effect of Rho-kinase inhibitor fasudil on the development of PH secondary to left ventricular dysfunction. Subsequently, in rats subjected to aortic banding for 6 weeks, there were increases in mean pulmonary arterial pressure, pulmonary arteriolar medial thickness, active RhoA, Rho-kinase II, Rho-kinase activity, endothelial nitric oxide synthase (eNOS) and endothelin-1(ET-1) concomitant with decreased levels in NO and cGMP in the lung. Treatment with fasudil at a dose of 30 mg/kg/day from days 1 to 28 or from days 29 to 42 decreased the mean pulmonary arterial pressure by 57% and 56%, right ventricular hypertrophy by 31% and 30%, pulmonary arteriolar medial thickness by 50% and 50%, and pulmonary expression of Rho-kinase II by 41% and 28%, respectively, as well as augmented pulmonary expression of eNOS by 16% and 31% and NO by 50% and 76%, respectively, when compared with the vehicle controls. In conclusion, these results suggest that inhibition of Rho-kinase may provide therapeutic potential for preventing and attenuating the development of PH in left ventricular dysfunction. Further translational study in human is needed to substantiate the findings.
Randomized trial of tofacitinib in active ulcerative colitis: analysis of efficacy based on patient-reported outcomes (2015)

Short-term treatment with tofacitinib BID was associated with dose-dependent improvement in health-related quality of life and patient preferences for tofacitinib. The results complement previously reported efficacy and safety data for the Phase II study. (NCT 00787202, November 6, 2008).
Tetrameric Bacterial Sodium Channels: Characterization of Structure, Stability, and Drug Binding (2008)

NaChBac from Bacillus halodurans is a bacterial homologue of mammalian voltage-gated sodium channels. It has been proposed that a NaChBac monomer corresponds to a single domain of the mammalian sodium channel and that, like potassium channels, four monomers form a tetrameric channel. However, to date, although NaChBac has been well-characterized for functional properties by electrophysiological measurements on protein expressed in tissue culture, little information about its structural properties exists because of the difficulties in expressing the protein in large quantities. In this study, we present studies on the overexpression of NaChBac in Escherichia coli, purification of the functional detergent-solubilized channel, its identification as a tetramer, and characterization of its secondary structure, drug binding, and thermal stability. These studies are correlated with a model produced for the protein and provide new insights into the structure-function relationships of this sodium channel.
Tricks of the trade used to accelerate high‐resolution structure determination of membrane proteins (2010)

The rate at which X-ray structures of membrane proteins are solved is on a par with that of soluble proteins in the late 1970s. There are still many obstacles facing the membrane protein structural community. Recently, there have been several technical achievements in the field that have started to dramatically accelerate structural studies. Here, we summarize these so-called 'tricks-of-the-trade' and include case studies of several mammalian transporters.
A soluble, single-chain T-cell receptor fragment endowed with antigen-combining properties. (1991)

A strategy for the production of small, soluble, single-chain T-cell receptor (scTCR) fragments that carry an intact TCR antigen-combining site is presented. The rationale is based on structural similarity between TCR and antibody molecules and use of computer modeling methods to derive a model structure of a human scTCR variable (V)-domain dimer. A gene encoding the RFL3.8 TCR protein, specific for the hapten fluorescein in the context of major histocompatibility complex class II and composed of one V alpha and one V beta domain joined via a flexible peptide linker, was assembled in an Escherichia coli plasmid. Subsequently, the protein was produced in a bacterial expression system, purified, refolded, and found to be poorly soluble at neutral pH in aqueous buffers. An inspection of the computer-generated V alpha-V beta domain model showed several surface exposed hydrophobic residues. When these were replaced by water-soluble side chains via site-directed mutagenesis of the corresponding gene, a soluble protein resulted and was shown to have antigen-binding properties equivalent to those of the intact TCR of the RFL3.8 T-cell clone. These results demonstrate the feasibility of obtaining TCR fragments endowed with antigen-combining properties by protein engineering in E. coli.
Section 10(b) and Rule 10b-5 Federal Securities Law Claims: The Need for the Uniform Disposition of the Arbitration Issue (1987)

This Comment examines the use of pre-dispute arbitration clauses in investment contracts. The author argues that, while the United States Arbitration Act mandates the enforcement of arbitration agreements, many courts have refused to enforce investment contract arbitration clauses fearing a lack of investor protection. The author reviews the use of arbitration in the securities industry, as well as the judicial decisions that have impacted its use. The author concludes that, with certain changes in the structure of these clauses, securities industry arbitration clauses should be enforced in order to protect investors and provide a more efficient method of resolving securities disputes.
GLUT1 deficiency syndrome – 2007 update (2007)

GLUT1 deficiency syndrome (GLUT1DS, OMIM 606777) is a treatable epileptic encephalopathy resulting from impaired glucose transport into the brain. The essential biochemical finding is a low glucose concentration in the cerebrospinal fluid (CSF; hypoglycorrhachia; mean 1.7 [SD 0.3mmol/L]) in the setting of normoglycaemia. CSF lactate is normal. Patients present with an early-onset epilepsy resistant to anticonvulsants, developmental delay, and a complex movement disorder. Hypotonic, ataxic, and dystonic features are most prominent. Speech is often severely affected. Some patients develop spasticity and secondary microcephaly. The phenotype is highly variable ranging from severe impairment to children without seizures. Electroencephalography (EEG) may show 2.5-4Hz spike-waves improving on food intake. Neuroimaging is uninformative. Most patients carry heterozygous de novo mutations in the GLUT1 gene (OMIM 138140, gene map locus 1p35-31.3). Autosomal dominant transmission and several mutational hot spots have been identified, but phenotype-genotype correlations are not yet apparent. Homozygous GLUT1 mutations presumably are lethal. The ketogenic diet is the treatment of choice as it provides an alternative fuel to the brain. It should be introduced early and maintained into puberty. Seizures are effectively controlled with the onset of ketosis, but might recur and require comedication. The effect on neurodevelopment appears less impressive. The increasing number of patients, molecular and biochemical analysis, recent research into ketogenic diet mechanisms, and the development of animal models for GLUT1DS have brought substantial insights in disease manifestations and mechanisms. This review summarizes data on 84 published cases and highlights recent advances in understanding this entity.
N-Linked Glycosylation in Campylobacter jejuni and Its Functional Transfer into E. coli (2002)

N-linked protein glycosylation is the most abundant posttranslation modification of secretory proteins in eukaryotes. A wide range of functions are attributed to glycan structures covalently linked to asparagine residues within the asparagine-X-serine/threonine consensus sequence (Asn-Xaa-Ser/Thr). We found an N-linked glycosylation system in the bacterium Campylobacter jejuni and demonstrate that a functional N-linked glycosylation pathway could be transferred into Escherichia coli. Although the bacterial N-glycan differs structurally from its eukaryotic counterparts, the cloning of a universal N-linked glycosylation cassette in E. coli opens up the possibility of engineering permutations of recombinant glycan structures for research and industrial applications.
Identification and characterization of the Escherichia coli RecT protein, a protein encoded by the recE region that promotes renaturation of homologous single-stranded DNA (1993)

Recombination of plasmid DNAs and recombination of bacteriophage lambda red mutants in recB recC sbcA Escherichia coli mutants, in which the recE region is expressed, do not require recA. The recE gene is known to encode exonuclease VIII (exoVIII), which is an ATP-independent exonuclease involved in the RecE pathway of recombination. A 33,000-molecular-weight (MW) protein was observed to be coexpressed with both exoVIII and a truncated version of exoVIII, pRac3 exo, when they were overproduced under the control of strong promoters. We have purified this 33,000-MW protein (p33) and demonstrated by protein sequence analysis that it is encoded by the same coding sequence that encodes the C-terminal 33,000-MW portion of exoVIII. p33 is expressed independently of exoVIII but is probably translated from the same mRNA. p33 was found to bind to single-stranded DNA and also to promote the renaturation of complementary single-stranded DNA. It appears that p33 is functionally analogous to the bacteriophage lambda beta protein, which may explain why RecE pathway recombination does not require recA.
Isolation and characterization of the human tyrosine hydroxylase gene: identification of 5' alternative splice sites responsible for multiple mRNAs (1987)

A full-length genomic clone for human tyrosine hydroxylase (L-tyrosine, tetrahydropteridine:oxygen oxidoreductase, EC 1.14.16.2) has been isolated. A human brain genomic library constructed in EMBL3 was screened by using a rat cDNA for tyrosine hydroxylase as a probe [Brown, E. R., Coker, G. T., III, & O'Malley, K. L. (1987) Biochemistry 26, 5208-5212]. Out of one million recombinant phage, one clone was identified that hybridized to both 5' and 3' rat cDNA probes. Restriction endonuclease mapping. Southern blotting, and sequence analysis revealed that, like its rodent counterpart, the human gene is single copy, contains 13 primary exons, and spans approximately 8 kilobases (kb). In contrast to the rat gene, human tyrosine hydroxylase undergoes alternative RNA processing within intron 1, generating at least three distinct mRNAs. A comparison of the human tyrosine hydroxylase and phenylalanine hydroxylase [DiLella, A. G., Kwok, S. C. M., Ledley, F. D., Marvit, J., & Woo, S. L. C. (1986) Biochemistry 25, 743-749] genes indicates that although both probably evolved from a common ancestral gene, major changes in the size of introns have occurred since their divergence.
Validation of a physically-based solid oxide fuel cell anode model combining 3D tomography and impedance spectroscopy (2016)

This study presents a physically-based model for the simulation of impedance spectra in solid oxide fuel cell (SOFC) composite anodes. The model takes into account the charge transport and the charge-transfer reaction at the three-phase boundary distributed along the anode thickness, as well as the phenomena at the electrode/electrolyte interface and the multicomponent gas diffusion in the test rig. The model is calibrated with experimental impedance spectra of cermet anodes made of nickel and scandia-stabilized zirconia and satisfactorily validated in electrodes with different microstructural properties, quantified through focused ion beam SEM tomography. Besides providing the material-specific kinetic parameters of the electrochemical hydrogen oxidation, this study shows that the correlation between electrode microstructure and electrochemical performance can be successfully addressed by combining physically-based modelling, impedance spectroscopy and 3D tomography. This approach overcomes the limits of phenomenological equivalent circuits and is suitable for the interpretation of experimental data and for the optimisation of the electrode microstructure.
In situ injection of kainic acid: A new method for selectively lesioning neuronal cell bodies while sparing axons of passage (1978)

Abstract The morphologic sequelae following stereotaxic injection into the rat striatum of kainic acid, a conformationally restricted analogue of glutamate, were examined by means of bright fields, histofluorescence and electron microscopic techniques. The neuropathologic response to kainate injection occurs in two distinct phases. Fist, the intrinsic neurons of the striatum undergo a rapid degeneration during the first 48 hours after injection; this is characterized by the sequential loss of cytoplasmic Nissl‐substance (chromatolysis), shrinkage of the perikarya, clumping of the nuclear chromatin and finally disruption of the nuclear membrane. Between one and three weeks after injection, a marked proliferation of astrocytes in the gray matter formerly populated by neurons characterizes the second phase. The region of several neuronal loss in the kainate injected stratum is approximately spherical in shape, and its extent is non‐linearly related to the amount of kainate injected. The neuropil of the injected striatum is markedly disrupted due to the death of intrinsic neurons and loss of their processes. Yet, histofluoresence microscopy demonstrates that the dopaminergic axons projecting from the substantia nigra do not degenerate in the kainate injected striatum; electron microscopic studies indicate that corticofugal fibers traversing the striatum also unaffected by kainate. Many presynaptic boutons, presumably of extrinsic origin, are intact up to ten days after injection; osmophilic vestiges of postsynaptic elements remain adherent to these boutons. Numerous phagocytic astrocytes are observed throughout the lesioned area. These morphologic studies provide (direct) evidence that in situ injection of kainic acid in brain causes a selective degeneration of neurons with cell bodies in the area of the injection but spares axons that arise from perikarya outside the region but pass through or terminate in the injected area. Thus, in situ injection of kainic acid is a new technique for making selective brain lesions that will be useful for examining neuronal connectivity.
Ontogeny of the Kidney and Renal Developmental Markers in the Rhesus Monkey (Macaca Mulatta) (2010)

Nonhuman primates share many developmental similarities with humans, thus they provide an important preclinical model for understanding the ontogeny of biomarkers of kidney development and assessing new cell-based therapies to treat human disease. To identify morphological and developmental changes in protein and RNA expression patterns during nephrogenesis, immunohistochemistry and quantitative real-time PCR were used to assess temporal and spatial expression of WT1, Pax2, Nestin, Synaptopodin, alpha-smooth muscle actin (α-SMA), CD31, vascular endothelial growth factor (VEGF), and Gremlin. Pax2 was expressed in the condensed mesenchyme surrounding the ureteric bud and in the early renal vesicle. WT1 and Nestin were diffusely expressed in the metanephric mesenchyme, and expression increased as the Pax2-positive condensed mesenchyme differentiated. The inner cleft of the tail of the S-shaped body contained the podocyte progenitors (visceral epithelium) that were shown to express Pax2, Nestin, and WT1 in the early second trimester. With maturation of the kidney, Pax2 expression diminished in these structures, but was retained in cells of the parietal epithelium, and as WT1 expression was upregulated. Mature podocytes expressing WT1, Nestin, and Synaptopodin were observed from the mid-third trimester through adulthood. The developing glomerulus was positive for α-SMA (vascular smooth muscle) and Gremlin (mesangial cells), CD31 (glomerular endothelium), and VEGF (endothelium), and showed loss of expression of these markers as glomerular maturation was completed. These data form the basis for understanding nephrogenesis in the rhesus monkey and will be useful in translational studies that focus on embryonic stem and other progenitor cell populations for renal tissue engineering and repair.
Mode of action of GR69153, a novel catechol-substituted cephalosporin, and its interaction with the tonB-dependent iron transport system (1990)

GR69153 is a novel cephalosporin incorporating a catechol-substituted 7-aminothiazolyl-oxime. The antibiotic is actively transported into gram-negative cells via iron-regulated outer membrane proteins regulated by the tonB product. This transport enhances bactericidal activity most significantly at low concentrations, essentially removing the permeability barrier for antibiotic uptake.
Norovirus (NoV) specific protective immune responses induced by recombinant P dimer vaccine are enhanced by the mucosal adjuvant FlaB (2016)

We validate the use of TLR5 agonist as a strong mucosal adjuvant that would facilitate the development of NoV specific vaccines for humans and veterinary use. This study also highlights the importance of route of immunization in inducing the appropriate immune responses in mucosal compartments.
ChemInform Abstract: Catalyzed Baeyer—Villiger Reactions (1998)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Microchip Technology for Automated and Parallel Patch‐Clamp Recording (2006)

The patch-clamp technique is the state-of-the-art technology for the study of a large class of membrane proteins called ion channels. Ion channels mediate electrical current flow, have crucial roles in cellular physiology, and are important drug targets. However, patch clamping is a laborious process requiring a skilled experimenter and is, therefore, not compatible with the high throughput needed in drug development. The solution for automated and parallel patch-clamp measurements that is provided by microchip technology is presented here.
Spectral phase optimization of femtosecond laser pulses for narrow-band, low-background nonlinear spectroscopy (2005)

We use experimental search space mapping to examine the problem of selective nonlinear excitation with binary phase shaped femtosecond laser pulses. The search space maps represent a graphical view of all the possible solutions to the selective nonlinear excitation problem along with their experimental degrees of success. Using the information learned from these maps, we generate narrow lines with low background in second harmonic generation and stimulated Raman scattering spectra.
Arbeit in Call Centern: soziologische und linguistische Stil-Analysen als konvergente Perspektivenauf neue Arbeitsformen (2003)

'Die Analyse von Kommunikationsarbeit wird bislang aus der spezifischen Perspektive einzelner Disziplinen betrieben. Der vorliegende Beitrag verfolgt demgegenüber das Ziel einer fachübergreifenden Perspektive, in dem das Tätigkeitsfeld am Beispiel von Call-Center-Arbeit aus zwei Richtungen, der Arbeitssoziologie und der pragmatischen Sprachwissenschaft, integrativ behandelt wird. Anhand der in beiden Wissenschaftsgebieten gängigen Kategorie 'Stil' werden Konvergenzen zwischen individuellem Arbeits- und Sprachhandeln herausgearbeitet. Dazu wird einerseits das Konzept des personalen Arbeitsstils herangezogen, andererseits auf der Grundlage des Konzepts Kommunikationsstil eine Analyse von Gesprächsmitschnitten unternommen. Der Artikel schließt mit kurzen Überlegungen zu methodischen Aspekten sowie sozialen Verwerfungen der Kommunikationsarbeit.' (Autorenreferat)
Clinical Impact of Gene Expression Profiling on Oncology Diagnosis, Prognosis, and Treatment (2004)

Genomics has enabled the examination of the totality of disease at the transcriptome level. Dependent upon a myriad of genetic aberrations for its pathogenesis, cancer has been the focus of gene expression profiling studies that have highlighted the potential clinical applications of this technology. This type of molecular profiling has the potential to enhance the ability of pathologists and oncologists to correctly classify tumors, not just into existing subgroups which may or may not have clear prognostic implications, but into new groups which carry predictable correlations with outcomes. Ultimately, these outcome predictions can be tied to specific treatment regimens, allowing clinicians to predict at the time of diagnosis to which therapy a given patient may best respond. Although this ultimate goal of personalized therapy remains in the future, the numerous studies to date have clearly demonstrated the overall feasibility of this approach. This review will showcase a few of these studies in several key tumor types with the goal of demonstrating which type of studies have been conducted and what types of results are currently possible.
Business process verification – finally a reality! (2009)

Purpose The purpose of this paper is to demonstrate that process verification has matured to a level where it can be used in practice. This paper reports on new verification techniques that can be used to assess the correctness of real‐life models. Design/methodology/approach The proposed approach relies on using formal methods to determine the correctness of business processes with cancellation and OR‐joins. The paper also demonstrates how reduction rules can be used to improve the efficiency. These techniques are presented in the context of the workflow language yet another workflow language (YAWL) that provides direct support for 20 most frequently used patterns found today (including cancellation and OR‐joins). But the results also apply to other languages with these features (e.g. BPMN, EPCs, UML activity diagrams, etc.). An editor has been developed that provides diagnostic information based on the techniques presented in this paper. Findings The paper proposes four properties for business processes with cancellation and OR‐joins, namely: soundness, weak soundness, irreducible cancellation regions and immutable OR‐joins and develop new techniques to verify these properties. Reduction rules have been used as a means of improving the efficiency of the algorithm. The paper demonstrates the feasibility of this verification approach using a realistic and complex business process, the visa application process for general skilled migration to Australia, modelled as a YAWL workflow with cancellation regions and OR‐joins. Originality/value Business processes sometimes require complex execution interdependencies to properly complete a process. For instance, it is possible that certain activities need to be cancelled mid‐way though the process. Some parallel activities may require complex “wait and see” style synchronisation depending on a given context. These types of business processes can be found in various domains, such as application integration, B2B commerce, web service composition and workflow systems. Even though cancellation and sophisticated join structures are present in many business processes, existing verification techniques are unable to deal with such processes. Hence, this paper plays an important role in making process verification a reality.