gebhart/patrepeval huggingface dataset:
Definitions and Guidelines for Assessment of Wounds and Evaluation of Healing (1994)

The report that follows defines wound, acute wound, chronic wound, healing and forms of healing, wound assessment, wound extent, wound burden, and wound severity. The utility of these definitions is demonstrated as they relate to the healing of a skin wound, but these definitions are broadly applicable to all wounds.
Intestinal and Cerebral Oxygenation during Severe Isovolemic Hemodilution and Subsequent Hyperoxic Ventilation in a Pig Model (2002)

During isovolemic hemodilution, the diminished oxygen supply was redistributed in favor of organs with a lower capacity to increase oxygen extraction. It is hypothesized that redirection of the oxygen supply within the intestines resulted in the preservation of oxygen consumption and mucosal muPo(2) compared with serosal muPo(2).
Local Expression of B7-H4 by Recombinant Adenovirus Transduction in Mouse Islets Prolongs Allograft Survival (2009)

Local expression of B7-H4 prolongs islet allograft survival in vivo, suggesting translational potential for beta-cell replacement with reduced immune injury.
InGaAs/InGaAsP MQW electroabsorption modulator integrated with a DFB laser fabricated by band-gap energy control selective area MOCVD (1993)

The fabrication and basic characteristics of a InGaAs/InGaAsP multi-quantum-well (MQW) electroabsorption modulator with a novel structure integrated with a distributed-feedback (DFB) laser are presented. A fundamental study was performed on the applicability of the InGaAs/InGaAsP MQW structure to an electroabsorption-type modulator. Efficient attenuation small hole pileup and small chirp characteristics of a discrete modulator based on this MQW structure were demonstrated experimentally. A study of the controllability of in-plane band-gap energy by the use of selective-area metal-organic chemical vapor deposition (MOCVD) was also demonstrated. The modulator was monolithically integrated with a MQW DFB laser of the same material. Using a low-capacitance semi-insulating buried heterostructure, over 14 GHz modulation under high-light-output operations up to +10 dBm was achieved. Modulation at 10 Gb/s with a modulation voltage swing of only 1 V/sub pp/ demonstrates the potential value of this system for 1.55- mu m lightwave communications.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Evolution of DNA Methylation Is Linked to Genetic Aberrations in Chronic Lymphocytic Leukemia (2013)

Although clonal selection by genetic driver aberrations in cancer is well documented, the ability of epigenetic alterations to promote tumor evolution is undefined. We used 450k arrays and next-generation sequencing to evaluate intratumor heterogeneity and evolution of DNA methylation and genetic aberrations in chronic lymphocytic leukemia (CLL). CLL cases exhibit vast interpatient differences in intratumor methylation heterogeneity, with genetically clonal cases maintaining low methylation heterogeneity and up to 10% of total CpGs in a monoallelically methylated state. Increasing methylation heterogeneity correlates with advanced genetic subclonal complexity. Selection of novel DNA methylation patterns is observed only in cases that undergo genetic evolution, and independent genetic evolution is uncommon and is restricted to low-risk alterations. These results reveal that although evolution of DNA methylation occurs in high-risk, clinically progressive cases, positive selection of novel methylation patterns entails coevolution of genetic alteration(s) in CLL.
mShal, a subfamily of A-type K+ channel cloned from mammalian brain. (1991)

We have cloned and expressed a mouse brain cDNA, mShal, that encodes a transient, A-type K+ current. mShal, the vertebrate homolog of the Drosophila Shal gene, defines a distinct subfamily of voltage-gated K+ channels. The Shal deduced proteins are more highly conserved between mouse and Drosophila than other presently known K+ channels. mShal carries a "low-threshold" A-type current with a hyperpolarized steady-state inactivation midpoint. Marked similarity was observed between mShal and its Drosophila homolog, fShal, with regard to voltage sensitivity of activation, macroscopic inactivation, steady-state inactivation, and 4-aminopyridine sensitivity. Sequence conservation for Shal proteins is unusually high at the amino terminus, an area considered important for inactivation. Removal of conserved amino-terminal residues from mShal modifies macroscopic inactivation but the transient nature of the current is preserved. Underlying the very high conservation of mShal and fShal may be a role in the nervous system that is conserved in widely divergent species.
Mechanism-Based Inhibitor Discrimination in the Acyl-CoA Dehydrogenases (1997)

The catalytically essential glutamate base in the acyl-CoA dehydrogenase family is found either on the loop between J and K helices (e.g., in short-chain, medium-chain, and glutaryl-CoA dehydrogenases) or on the G helix (long-chain and isovaleryl-CoA dehydrogenases). While active-site bases at either position are functionally equivalent with respect to alpha-proton abstraction, reactions that require removal of a gamma-proton show marked differences between the two enzyme classes. Thus short-chain, medium-chain, and glutaryl-CoA dehydrogenase are rapidly inactivated by 2-pentynoyl-CoA with abstraction of a gamma-proton, whereas isovaleryl-CoA dehydrogenase is not significantly inhibited. This resistance is not due to weak binding: the complex between isovaleryl-CoA dehydrogenase and 2-pentynoyl-CoA shows a Kd of 1.8 microM at pH 7.6. Migration of the catalytic base to the loop between J and K helices (using the Glu254Gly/Ala375Glu double mutant) makes isovaleryl-CoA dehydrogenase sensitive to irreversible inhibition by 2-pentynoyl-CoA. Molecular modeling suggests that this mutation brings the catalytic base close enough to abstract a gamma-proton from the bound inhibitor. Experiments with two mechanism-based inactivators that target the FAD of the medium- and short-chain acyl-CoA dehydrogenases support this conclusion. 3-Methyl-3-butenoyl-CoA requires activation by alpha-proton abstraction and rapidly yields a reduced flavin adduct with wild-type isovaleryl-CoA dehydrogenase. In contrast, the isomeric 3-methyl-2-butenoyl-CoA is inert toward this enzyme because it cannot be activated by gamma-proton abstraction. Molecular modeling supports these observations. This unusual selectivity toward mechanism-based inactivators provides additional discrimination between members of the acyl-CoA dehydrogenase family.
Integrated Signals Between IL-13, IL-4, and IL-5 Regulate Airways Hyperreactivity (2000)

In this investigation, we have examined the integrated relationship between IL-13, IL-4, and IL-5 for the development of airways hyperreactivity (AHR) in a model of asthma in BALB/c mice. Sensitization and aeroallergen challenge of both wild-type (WT) and IL-13 gene-targeted (IL-13-/-) mice induced allergic disease that was characterized by pulmonary eosinophilia and AHR to beta-methacholine. Although these responses in IL-13-/- mice were heightened compared with WT, they could be reduced to the level in nonallergic mice by the concomitant neutralization of IL-4. Mice in which both IL-4 and IL-13 were depleted displayed a marked reduction in tissue eosinophils, despite the development of a blood eosinophilia. Similar neutralization of IL-4 in WT mice only partially reduced AHR with no effect on tissue eosinophilia. In addition, neutralization of IL-5 in IL-13-/- mice, but not in WT mice, inhibited AHR, suggesting that tissue eosinophilia is linked to the mechanism underlying AHR only in the absence of IL-13. Additionally, mucus hypersecretion was attenuated in IL-13-/- mice, despite the persistence of AHR. Taken together, our data suggest both a modulatory role for IL-13 during sensitization and a proinflammatory role during aeroallergen challenge. The latter process appears redundant with respect to IL-4.
Spheroidal aggregate culture of rat liver cells: histotypic reorganization, biomatrix deposition, and maintenance of functional activities. (1985)

Liver cells isolated from newborn rats and seeded on a non-adherent plastic substratum were found to spontaneously re-aggregate and to form, within a few days, spheroidal aggregates that eventually reached a plateaued diameter of 150-175 micron. Analyses on frozen sections from these spheroids by immunofluorescence microscopy using antibodies to various cytoskeletal elements and extracellular matrix components revealed a sorting out and a histotypic reorganization of three major cell types. A first type consisted of cells that segregated out on the aggregate surface forming a monolayer cell lining; a second type was identified as hepatocytes that regrouped in small islands often defining a central lumen; and a third group of cells reorganized into bile duct-like structures. This intercellular organization in the aggregates was paralleled by the accumulation of extracellular matrix components (laminin, fibronectin, and collagen) and their deposition following a specific pattern around each cell population structure. Determinations of albumin secretion and tyrosine aminotransferase induction by dexamethasone and glucagon at various times after the initiation of the cultures revealed a maintenance of the hepatocyte-differentiated functions for at least up to 2 mo at the levels measured at 3-5 d. It is concluded that cells dispersed as single cells from newborn rat liver conserve in part the necessary information to reconstruct a proper three-dimensional cyto-architecture and that the microenvironment so generated most likely represents a basic requirement for the optimal functioning of these differentiated cells.
Optimized particle-mesh Ewald/multiple-time step integration for molecular dynamics simulations (2001)

We develop an efficient multiple time step (MTS) force splitting scheme for biological applications in the AMBER program in the context of the particle-mesh Ewald (PME) algorithm. Our method applies a symmetric Trotter factorization of the Liouville operator based on the position-Verlet scheme to Newtonian and Langevin dynamics. Following a brief review of the MTS and PME algorithms, we discuss performance speedup and the force balancing involved to maximize accuracy, maintain long-time stability, and accelerate computational times. Compared to prior MTS efforts in the context of the AMBER program, advances are possible by optimizing PME parameters for MTS applications and by using the position-Verlet, rather than velocity-Verlet, scheme for the inner loop. Moreover, ideas from the Langevin/MTS algorithm LN are applied to Newtonian formulations here. The algorithm’s performance is optimized and tested on water, solvated DNA, and solvated protein systems. We find CPU speedup ratios of over 3 for Newtonian formulations when compared to a 1 fs single-step Verlet algorithm using outer time steps of 6 fs in a three-class splitting scheme; accurate conservation of energies is demonstrated over simulations of length several hundred ps. With modest Langevin forces, we obtain stable trajectories for outer time steps up to 12 fs and corresponding speedup ratios approaching 5. We end by suggesting that modified Ewald formulations, using tailored alternatives to the Gaussian screening functions for the Coulombic terms, may allow larger time steps and thus further speedups for both Newtonian and Langevin protocols; such developments are reported separately.
Grafting of Vinyl‐Type Polynorbornene on Polybutadiene and Polyisoprene (2002)

Abstract High molecular weight vinyl‐type polynorbornene was obtained by polymerization of norbornene initiated by [NiBr(NPMe 3 )] 4 /B(C 6 F 5 ) 3 . Polymerization in the presence of olefins resulted in termination of polynorbornene chains by olefinic moieties. Molecular weights of polynorbornenes terminated by vinylidene compounds are lower than those terminated by vinyl and vinylene compounds. Corresponding polymerizations with polybutadiene and polyisoprene yielded graft copolymers with polynorbornene as grafts without contamination by homopolymerized polynorbornene. Grafting reactions were proved by spectroscopy, GPC, and degradation experiments using OsO 4 . GPC traces (refractometer detector) of PN obtained for the polymerizations of 2 in the presence of 4d . magnified image GPC traces (refractometer detector) of PN obtained for the polymerizations of 2 in the presence of 4d .
Defective expression of Notch1 and Notch2 in connection to alterations of c-Myc and Ikaros in -radiation-induced mouse thymic lymphomas (2004)

Gamma-radiation-induced thymic lymphomas constitute a heterogeneous group of T-cell lymphomas. Some tumour suppressor genes and oncogenes have been shown to be defective in a fraction of such lymphomas, yet a considerable number of these remain elusive in terms of gene alterations. In the present work we present evidence that gamma-radiation-induced thymic lymphomas in (C57BL/6 J x BALB/c) F1 hybrid mice often exhibit increased levels of Notch1 expression, but, contrary to what was expected, they also exhibit a clearly reduced Notch2 mRNA expression, suggesting a cooperative antagonism of these genes. These results represent the first reported instance for the involvement of Notch2 inactivation in the development of thymic primary tumours while confirming the role of Notch1 as an activated oncogene. Additional analyses revealed that c-Myc over-expression and partial inactivation of Znfn1a1/Ikaros appear to be relevant events some how coupled to alterations in Notch genes inducing these kinds of tumours.
Nerve growth factor induced hyperalgesia in the rat hind paw is dependent on circulating neutrophils (1998)

The mechanisms by which nerve growth factor (NGF) induces thermal hyperalgesia and neutrophil accumulation have been investigated in the rat. Thermal nociceptive thresholds in rat hind paw were measured as the time taken for paw withdrawal from a heat source and neutrophil accumulation was measured in hind paw and dorsal skin samples using a myeloperoxidase assay. NGF (23-80 pmol intraplantar (i.pl.) injection) induced a significant (P < 0.05, n = 6-16) thermal hyperalgesia at 5 h after injection and significant neutrophil accumulation (P < 0.05, n = 6) was observed with NGF (40 pmol). In dorsal skin, where multiple samples can be assessed, intradermal (i.d.) NGF was 10-30 times less potent than interleukin-1beta in inducing neutrophil accumulation. The 5-lipoxygenase inhibitor ZM230487 (10 nmol co-injected with NGF) significantly attenuated neutrophil accumulation and hyperalgesia induced by NGF; unlike the histamine and 5-hydroxytryptamine antagonists (mepyramine and methysergide) which were without effect at the times measured. Furthermore, depletion of circulating neutrophils (using a rabbit anti-rat neutrophil antibody) abolished NGF induced hyperalgesia. These results indicate that neutrophils, which accumulate in response to a 5-lipoxygenase product, play a crucial role in NGF-induced hyperalgesia.
Metformin induces apoptosis of pancreatic cancer cells (2008)

Metformin significantly inhibits cell proliferation and apoptosis in all pancreatic cell lines. And the metformin-induced apoptosis is associated with PARP cleavage, activation of caspase-3, -8, and -9 in a time- and dose-dependent manner. Hence, both caspase-8 and -9-initiated apoptotic signaling pathways contribute to metformin-induced apoptosis in pancreatic cell lines.
Droplet-Based Microfluidics: Enabling Impact on Drug Discovery (2013)

Over the past two decades, the application of microengineered systems in the chemical and biological sciences has transformed the way in which high-throughput experimentation is performed. The ability to fabricate complex microfluidic architectures has allowed scientists to create new experimental formats for processing ultra-small analytical volumes in short periods and with high efficiency. The development of such microfluidic systems has been driven by a range of fundamental features that accompany miniaturization. These include the ability to handle small sample volumes, ultra-low fabrication costs, reduced analysis times, enhanced operational flexibility, facile automation, and the ability to integrate functional components within complex analytical schemes. Herein we discuss the impact of microfluidics in the area of high-throughput screening and drug discovery and highlight some of the most pertinent studies in the recent literature.
Antimicrobial susceptibility and molecular epidemiology of beta-lactamase-producing, aminoglycoside-resistant isolates of Enterococcus faecalis (1991)

beta-Lactamase-producing (BL+), aminoglycoside-resistant (AR) Enterococcus faecalis is endemic in our hospital, having caused widespread colonization and infection. Suitable therapy for infections caused by these organisms has been problematic. We compared the antimicrobial and bactericidal activities, by broth macrodilution and time-kill methods, of several antibiotics, alone and in combination, against BL+, AR isolates of E. faecalis and determined the transmissibility of antibiotic resistance markers. Ampicillin-sulbactam, imipenem, daptomycin, and ciprofloxacin were the most active antibiotics with MICs for 90% of isolates tested of 2, 1, 2, and 1 microgram/ml, respectively, against inocula of 10(3) and 10(5) CFU/ml. Little inoculum effect was noted with imipenem, vancomycin, daptomycin, or ciprofloxacin, while the addition of sulbactam to ampicillin partially inhibited the effect of the increased inoculum. Penicillin-sulbactam and ampicillin-sulbactam combinations in a 2:1 ratio were most frequently bactericidal (greater than or equal to 3-log10-unit decrease in bacterial titers at 24 h for 13 of 20 isolates), followed by daptomycin (8 of 20 isolates) and ciprofloxacin (2 of 20 isolates). Bactericidal activity was not demonstrated for imipenem or teicoplanin. beta-Lactamase production and aminoglycoside resistance were associated with a 60- to 65-MDa plasmid which was easily transferred to a plasmid-free E. faecalis recipient. The 840-bp beta-lactamase gene probe hybridized to purified plasmid DNA from BL+ donor isolates of E. faecalis and transconjugants but not from BL- isolates. Ampicillin-sulbactam and daptomycin (an investigational antibiotic) seem to be reasonable choices for the empiric therapy of presumed enterococcal infections in hospitals in which BL+, AR E. faecalis strains are isolated. Their use should ideally be supported by tests for bactericidal activity.
Visceral afferents: their contribution to ‘sympathetic dependent’ pain (1994)

For 80 years the sympathetic nervous system has been implicated in certain human pains, notably causalgia and reflex sympathetic dystrophy. This assumption has led to the accepted concept of 'sympathetic dependent' pain. In this critical review, the evidence for this assumption is assessed. It is found that the clinical phenomena suggesting sympathetic nerve involvement may be more satisfactorily attributed to effects of neuropeptides released from afferent C-fibres. The evidence also demonstrates that the effects resembling sympathetic dysfunction relate neither to the pain nor to pain relief following sympathetic blockade. The techniques and results of sympathetic blockade have rarely been adequately evaluated, and the apparent efficacy, specificity and mode of action of peripheral sympatholytic drugs are questioned. An alternative explanation is proposed: that visceral afferents subserve a number of human pains, including those that have been considered sympathetically mediated. Problems of terminology are discussed; use of the term 'visceral afferent' is clarified and broadened to include afferents, particularly those related to blood vessels, which travel within autonomic nerves, in addition to the classical visceral afferent innervation of the organs of the great body cavities. The clinico-anatomical evidence reviewed here indicates that this general and widespread system of afferents could subserve certain pains. The relationship between visceral afferents, somatic afferents and autonomic efferents is outlined, and support is found for the unitary nature of the sensory system envisaged by Langley. Conflicting results from experiments on animals and clinical studies in man on the pain-subserving properties of visceral afferents are summarized; these confirm that visceral afferents can, at least on occasions in man, mediate pain not considered typically 'visceral'. This conclusion receives support from a number of clinical observations: not only are diseases of the autonomic nervous system painless, but damage to previously painless autonomic nerves can generate pain, as illustrated by several different conditions; pain from diseases other than of the viscera of the great cavities and which involves the widespread visceral afferents may be alleviated by sympathetic blockade, presumably since afferents travelling within autonomic fibres are simultaneously blocked; and diseases which impair the function of autonomic nerves may be unexpectedly painless. The central nervous system sequelae following involvement of visceral afferents are outlined and found to be relevant to phenomena sometimes seen with causalgia and related conditions: spread of pain; mirror involvement; associated features such as involuntary movements; and referred pain. Visceral afferents are generally clinically silent unless damage occurs.(ABSTRACT TRUNCATED AT 400 WORDS)
Characterization of a component in chick ciliary ganglia that cross- reacts with monoclonal antibodies to muscle and electric organ acetylcholine receptor (1985)

Chick ciliary ganglion neurons have previously been shown to contain a component that shares an antigenic determinant with the "main immunogenic region" of the alpha-subunit in nicotinic acetylcholine receptor from skeletal muscle and electric organ. Ultrastructural studies of antibody binding in the ganglion have shown that the cross-reacting antigen exposed on the surface of the neurons is located predominantly in synaptic membrane. Here we show that the neuronal antigen can be identified in detergent extracts of ciliary and sympathetic ganglia, but not in extracts of heart, liver, spinal cord, retina, or dorsal root ganglia. In the ciliary ganglion the component is present as an integral membrane constituent, and, when detergent solubilized, it sediments as a 10 S species and binds to concanavalin A. The component is distinct from the alpha-bungarotoxin-binding site on the neurons since toxin-binding sites and antibody-binding sites can be precipitated separately in ganglion extracts. The component reaches peak levels per ganglionic protein between embryonic days 8 and 12. These are some of the properties expected for the nicotinic acetylcholine receptor on ciliary ganglion neurons.