gebhart/patrepeval huggingface dataset:
Liver transplantation induces cytochrome P450 1A1 dependent monooxygenase activity in rat lung and kidney (1995)

Although liver transplantation has been the subject of intensive investigation, comparatively little is known regarding the effects of this procedure on the metabolism of xenobiotics. The objective of the present study was to examine the effect of orthotopic liver transplantation on rat hepatic, pulmonary, and renal microsomal cytochrome P450 (P450) monooxygenase activity through the use of isozyme-selective substrates. Pulmonary microsomal P450 1A1 dependent 7-ethoxyresorufin O-deethylation (ERFD) activity increased over time in recipient rats, with maximal induction (750% of donor) observed after 21 days. Similarly, ERFD activity in renal microsomes was increased (200% of donor) after 21 days. Both pulmonary and renal microsomal P450 2B dependent 7-pentoxyresorufin O-depentylation (PRFD) activity was decreased (50 and 75% of donor) 1 day after transplantation but was essentially unchanged 3, 7, and 21 days after transplantation. Pulmonary and renal microsomal heme oxygenase activities were not significantly affected by liver transplantation. In contrast, total hepatic microsomal P450 concentrations were decreased maximally (to 45% of donor concentration) 7 days after transplantation and remained low (55% of donor) up to 21 days. Similarly, hepatic P450 1A dependent ERFD and P450 2B dependent PRFD activities were maximally depressed (20 and 25% of donor activities) after 7 days and remained low (75 and 30% of donor) up to 21 days after transplantation. The decreases in rates of hepatic P450 monooxygenation were accompanied by significant increases in microsomal heme oxygenase activity. The data presented in this study suggest the existence of generalized stress responses to inflammation that result in tissue- and isozyme-selective modulation of P450 monooxygenase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Structure-Based Design of Potent Inhibitors of Scytalone Dehydratase:  Displacement of a Water Molecule from the Active Site (1998)

Scytalone dehydratase (SD) is a molecular target of inhibitor design efforts aimed at protecting rice plants from the fungal disease caused by Magnaporthe grisea. As determined from X-ray diffraction data of an SD-inhibitor complex [Lundqvist et al. (1994) Structure (London) 2, 937-944], there is an extended hydrogen-bonding network between protein side chains, the inhibitor, and two bound water molecules. From models of SD complexed to quinazoline and benztriazine inhibitors, a new class of potent SD inhibitors involving the displacement of an active-site water molecule were designed. We were able to increase inhibitory potency by synthesizing compounds with a nitrile functionality displayed into the space occupied by one of the crystallographic water molecules. Sixteen inhibitors are compared. The net conversion of potent quinazoline and benztriazine inhibitors to cyanoquinolines and cyanocinnolines increased binding potency 2-20-fold. Replacement of the nitrile with a hydrogen atom lowered binding affinity 100-30,000-fold. X-ray crystallographic data at 1.65 A resolution on a SD-inhibitor complex confirmed that the nitrile functionality displaced the water molecule as intended and that a favorable orientation was created with tyrosines 30 and 50 which had been part of the hydrogen-bonding network with the water molecule. Additional data on inhibitors presented herein reveals the importance of two hydrogen-bonding networks toward inhibitory potency: one between Asn131 and an appropriately positioned inhibitor heteroatom and one between a bound water molecule and a second inhibitor heteroatom.
Effect of DHEA on Abdominal Fat and Insulin Action in Elderly Women and Men (2004)

DHEA replacement could play a role in prevention and treatment of the metabolic syndrome associated with abdominal obesity.
The Anaerobic Threshold: Definition, Physiological Significance and Identification (2015)

During exercise, the oxygen consumption above which aerobic energy production is supplemented by anaerobic mechanisms, causing a sustained increase in lactate and metabolic acidosis, is termed the anaerobic threshold (AT). The oxygen consumption at the AT depends on factors that affect oxygen delivery to the tissues. It is increased when oxygen flow is enhanced and decreased when oxygen flow is diminished. Its value is quite low in patients with heart disease. The AT is an important functional demarcation since the physiological responses to exercise are different above the AT compared to below the AT. Above the AT, in addition to the development of metabolic acidosis, exercise endurance is reduced, VO2 kinetics are slowed so that a steady state is delayed, and VE increases disproportionately to the metabolic requirement and a progressive tachypnea develops. The AT can be measured directly from the lactate concentration with precise threshold detection from a log-log transformation of lactate and VO2. This threshold also defines the VO2 above which the lactate/pyruvate ratio increases. As bicarbonate changes reciprocally with lactate, its measurement can also be used to estimate the lactate threshold. But most convenient are gas exchange measurements made during exercise testing which can be used to noninvasively detect the lactate or anaerobic threshold. These methods are based on the physical-chemical event of buffering lactic acid with bicarbonate, and the increased CO2 output which occurs in association with the acute development of a metabolic acidosis.
Neat macroscopic membranes of aligned carbon nanotubes (2003)

Thick macroscopic membranes of magnetically aligned single-wall carbon nanotubes (SWNT) have been produced via high pressure filtration of aqueous surfactant-suspended SWNT in a magnetic field, resulting in membrane thicknesses of 10 μm and surface areas of 125 cm2. Field strengths of 7 and 25 T were used. Polarized Raman spectroscopy shows an anisotropy of (2.5±0.5), indicating good alignment. A similar degree of alignment was seen at both intensities of magnetic field. Furthermore, the degree of alignment is comparable to that achieved in previous work that produced smaller and thinner membranes at 25 T. The membranes also exhibit uniform anisotropy across their surface and throughout their thickness.
Glycomics: New Challenges and Opportunities in Regenerative Medicine (2016)

Tissue engineering relies on the possibility to engineer cell microenvironments by means of bioactive materials, biochemical and physical stimuli in order to guide cell behaviour and to regenerate damaged tissue. Despite the relevance of glycan epitopes as signaling molecules, and the recent advances in glycomics, their use as biomolecular cues at the interface between materials and cells for the controlled stimulation of adhesion and differentiation processes for regenerative medicine applications is still limited. In this concept article we will briefly outline the basis and the impact on health and economics of regenerative medicine, together with the recent applications of the glycocode in tissue regeneration approaches.
Effect of Immune Reconstitution on Resistance to Brugia pahangi in Congenitally Athymic Nude Mice (1983)

The dichotomy of resistance to Brugia pahangi (Nematoda: Filarioidea) between nonsusceptible, euthymic C3H/HeN mice, heterozygotic for the "nu" gene (+/nu), and susceptible, congenitally-athymic "nude" (nu/nu) C3H/HeN mice, suggests that resistance is thymus-dependent. To test this hypothesis, the effect of syngeneic neonatal thymus grafts and neonatal thymus cell suspensions on recovery of worms at day 40 PI, and responses to Concanavalin A (Con A) were examined in reconstituted nudes. Nude recipients of a thymus graft 7 or 14 wk before subcutaneous inoculation with 50 infective larvae (L3) yielded no worms and responded strongly to Con A. Serum from these mice reacted in two lines of identity with serum from similarly-infected heterozygotes by double radial immunodiffusion against an adult worm saline extract. Nude recipients of a thymus 2 days or 3 wk before inoculation harbored an average of three or two worms, respectively. Intravenous injection of nude recipients with 10(7) or 10(8) neonatal thymus cells seven weeks before inoculation was less effective in conferring resistance to B. pahangi and responsiveness to Con A. Complete resistance to B. pahangi could be adoptively transferred to nude mice by 10(8) spleen cells obtained from infection-primed heterozygotes and injected intravenously on the day of larval inoculation. The same numbers of worms were significantly reduced. less effective when injected 3 wk before inoculation, although numbers of worms were significantly reduced. Passive transfer of primed heterozygote serum, containing high titers of antibodies to adult worm and larval antigens, failed to protect nude recipients against a larval inoculum in the absence of cellular reconstitution.(ABSTRACT TRUNCATED AT 250 WORDS)
A plasmid-encoded VEGF siRNA reduces glioblastoma angiogenesis and its combination with interleukin-4 blocks tumor growth in a xenograft mouse model (2006)

Angiogenesis is required for the development and biologic progression of glioblastoma multiform (GBM), which is the most malignant infiltrative astrocytoma. Vascular endothelial growth factor (VEGF) plays a predominant role in the increased vascularity and endothelial cell proliferation in GBMs driven by the expression of pro-angiogenic cytokines. In this study, we employed a vector-encoded VEGF siRNA to impair VEGF secretion from U87 human glioblastoma cells. The direct intra-tumor injection of a siRNA-encoding plasmid complexed with linear polyethylenimine (PEI) efficiently reduced the vascularization of treated tumors in xenografts established in SCID mice by subcutaneous inoculation of U87 cells, but was not able to reduce tumor growth. We then sought to strengthen the in vivo action of our siRNA by coupling it to a well known direct antiangiogenic agent, mouse interleukin 4 (mIL4). We infected U87 cells with a retroviral vector coexpressing the VEGF siRNA and mIL4 and produced stable cell lines that we used for an in vivo experiment of subcutaneous injection in SCID mice. In this setting, the concomitant expression of mIL4 and siRNA totally abolished the growth of subcutaneous tumors. These results suggest that our retroviral vector might be employed as a potential tool in future antiangiogenic gene therapy trials for glioblastoma.
Statistical mechanics of cellular automata (1983)

Cellular automata are used as simple mathematical models to investigate self-organization in statistical mechanics. A detailed analysis is given of "elementary" cellular automata consisting of a sequence of sites with values 0 or 1 on a line, with each site evolving deterministically in discrete time steps according to definite rules involving the values of its nearest neighbors. With simple initial configurations, the cellular automata either tend to homogeneous states, or generate self-similar patterns with fractal dimensions \ensuremath{\simeq} 1.59 or \ensuremath{\simeq} 1.69. With "random" initial configurations, the irreversible character of the cellular automaton evolution leads to several self-organization phenomena. Statistical properties of the structures generated are found to lie in two universality classes, independent of the details of the initial state or the cellular automaton rules. More complicated cellular automata are briefly considered, and connections with dynamical systems theory and the formal theory of computation are discussed.
Inhibition of Secretion of Hepatitis B Surface Antigen by a Related Presurface Polypeptide (1986)

The presurface (preS) proteins of hepatitis B virus are structural components of the viral envelope that may play important roles in virion assembly and infectivity. They are specified by a large open reading frame that includes the coding region for the major surface (S) protein in its 3' half. Translation of the preS proteins initiates upstream from the S region, giving rise to proteins that are composed of the S domain and an additional 163 (preS1) or 55 (preS2) amino acids. Little is known about the biosynthesis and assembly of these proteins. The expression of the S and preS1 proteins was examined by transfecting cultured mammalian cells with viral DNA and injecting synthetic messenger RNA's into Xenopus oocytes. In contrast to the proteins encoded by the S region, the preS1 proteins are not detectably secreted into the culture medium. Furthermore, when the S and preS1 proteins are synthesized together, secretion of the S proteins is specifically and strongly inhibited. The results suggest a unique molecular interaction during secretion of the S and preS proteins that may be important for virus assembly.
Processing of ultrahigh molecular weight polyethylene (1988)

Abstract The extent of recrystallization of nascent UHMWPE powder is easily measured by calorimetry. Melting and recrystallization of nascent UHMWPE at 140°C can be suppressed by compression molding. Crystals of UHMWPE prepared from dilute solution show a peak melting temperature of 140°C and exhibit crystallinity up to 75.5% depending on crystallization temperature. Large changes in crystallinity result from drawing single crystal mats or compression‐molded films.
Chemical warfare agents: toxicology and treatment (2007)

Opinions of Chemical Warfare. The Physicochemical Properties and General Toxicology of Chemical Warfare Agents. Organophosphate Nerve Agents. Treatment and Prophylaxis of Organophosphate Nerve Agent Poisoning. A History of Human Studies with Nerve Agents by the UK and USA. Mustard Gas. Organic Arsenicals. Phosgene. Cyanides. Riot-Control Agents. Appendices. Index.
Gefitinib (‘Iressa’, ZD1839) and new epidermal growth factor receptor inhibitors (2004)

The epidermal growth factor receptor (EGFR) is a promising target for cancer therapy and a number of EGFR-targeted agents have been developed. Those most advanced in development are the EGFR tyrosine kinase inhibitors gefitinib ('Iressa', ZD1839) and erlotinib ('Tarceva', OSI-774), and the monoclonal antibody cetuximab ('Erbitux', IMC-C225). This review provides a clinical overview of these agents, highlighting their antitumour activities in different tumour types. Epidermal growth factor receptor-targeted agents are generally well tolerated and are not typically associated with the severe adverse events often seen with cytotoxic chemotherapy. Gefitinib is the agent with the most extensive clinical experience, particularly in non-small-cell lung cancer (NSCLC). Recently, gefitinib became the first-approved EGFR-targeted agent, for use in patients with previously treated advanced NSCLC in Japan, the USA and other countries. Further studies are required to explore the full potential of these novel agents either as monotherapy or combination therapy.
Boronic Acids (2011)

Introduction: Properties, Preparation, Overview of Application Metal-Catalyzed Borylation of C-X and C-H Bonds for the Synthesis of Boronic Esters Transition-Metal Catalyzed Sila- and Diborylation of Alkenes, Allenes, and Alkynes The Contemporary Suzuki-Miyaura Reaction Rhodium and Palladium-Catalyzed Asymmetric Conjugate Additions of Organoboronic Acids Recent Advances in Chan-Lam Coupling Reaction: Copper-Promoted C-Heteroatom Bond Cross-Coupling Reactions with Boronic Acids and Derivatives Transition-Metal Catalyzed Desulfitative Coupling of Thioorganic Compounds with Boronic Acids Catalytic Additions of Allylic Boronates to Carbonyl and Imine Derivatives Recent Advances in Nucleophilic Addition Reactions of Organoboronic Acids and their Derivatives to Unsaturated C?N Functionalities Asymmetric Homologation of Boronic Esters with Lithiated Carbamates Organotrifluoroborates: Organoboron Reagents for the 21st Century Boronic Acids as Catalysts Applications of boronic acids in chemical biology and medicinal chemistry Boronic Acids in Materials Chemistry
Recent duplication of the two human CD8 beta-chain genes (1992)

Isolation of cDNA clones encoding the beta-chain of the human T cell surface glycoprotein CD8 revealed the presence of five distinct forms of cDNA resulting from alternative splicing. In the process of analysis of the gene organization, we found that there exist two recently duplicated genes for CD8 beta. These genes, designated CD8 beta 1 and beta 2, consist of nine and seven exons, respectively. The organization of CD8 beta 1 and beta 2 genes is almost identical except in their 3'-ends. There are nine nucleotide differences between the coding regions of the CD8 beta 1 and beta 2 genes in spite of the extremely high similarity of these genes which extends over the entire genes including introns. Pulse field gel analysis demonstrated that CD8 beta 1 and beta 2 genes are located more than 1.5 Mb apart. It was found that the CD8 beta 1 gene is approximately 25 kb upstream from the CD8 alpha gene in the same transcriptional orientation on chromosome 2. Although both CD8 beta 1 and beta 2 genes appear functional from the nucleotide sequence, the five distinct forms of CD8 beta cDNAs and corresponding mRNAs found in thymus, PBL, and leukemic cell line HPB-ALL are all derived by alternative splicing from CD8 beta 1 transcripts.
Reduction of channel resistance in amorphous oxide thin-film transistors with buried layer (2012)

A silicon-indium-zinc-oxide (SIZO) thin film transistor (TFT) with low channel-resistance (RCH) indium-zinc-oxide (In2O3:ZnO = 9:1) buried layer annealed at low temperature of 200°C exhibited high field-effect mobility (μFE) over 55.8 cm2/V·s which is 5 times higher than that of the conventional TFTs due to small threshold voltage (Vth) change of 1.8 V under bias-temperature stress (BTS) condition for 420 minutes. The low-RCH buried-layer allows more strong current-path formed in channel layer well within relatively high-RCH channel-layer since it is less affected by the channel bulk and/or back interface trap with high carrier concentration.
Distinct isoforms of neuregulin are expressed in mesenchymal and neuronal cells during mouse development. (1994)

Neuregulin, the putative ligand of the c-neu receptor tyrosine kinase, can induce differentiation or growth of epithelia and other cells. To gain insight into the biological role of this factor, we have analyzed the expression of neuregulin during mouse embryogenesis and in the perinatal animal by a combination of in situ hybridization and RNase protection experiments. We identify sites of expression that correspond to mesenchymal cells of various parenchymal organs. Our finding implies a function of neuregulin as a mesenchymal factor that acts on epithelia. The mesenchymal expression of neuregulin could thus provide a molecular basis for the biological phenomenon of mesenchymal-epithelial interactions. It also has implications on the molecular mechanism by which amplification of c-neu can affect tumor progression of carcinomas. In addition, neuregulin expression is found in neuronal cells during development. We show by RNase protection experiments that distinct isoforms of neuregulin are expressed in the brain. Therefore, our data indicate in vivo a dual role for neuregulin as mesenchymal and neuronal factor.
Rapid, Nonlinear System Identification for NDT, Using Sensor Response Databases (2008)

For many systems, accurately estimating multiple parameters or variables of interest from multiple sensor responses requires models that account for nonlinear system behavior. Such multivariate estimation is typically accomplished using iterative methods or local linearity assumptions in the vicinity of a nominal operating point. Here, an alternative approach is described in the context of nondestructive testing (NDT) where databases of precomputed sensor responses are used with error minimization methods to efficiently perform multiple unknown parameter estimations (Goldfine and Melcher, 1995; Goldfine and Melcher, 2002; Melcher, 1991). Databases are generated from forward models for the sensor response, requiring the sensor to be accurately modeled over the operating range of interest. The entire nonlinear response over a wide range of material or geometric properties as well as sensor design/operating conditions is captured and used in the inverse method. The sensor must be designed so that difficult-to-model (and other unmodeled) contributions to the sensor response are minimized. Specific applications for properly designed meandering winding magnetometer eddy current sensors and interdigitated electrode dielectrometer sensors are described. These sensors were specifically designed to minimize unmodeled contributions.
An emergent approach to systems of physical agents (1997)

For the past ten years the author has been involved in industrial research on applications of agent architectures to manufacturing, and is presently technical advisor to an industrial consortium that is fielding pilot tests of shop-floor agents. The specific problem addressed by most of their work is the management of material flow and resource utilization on the factory floor. Classically, these problems have been considered under the rubrics of ‘scheduling’ and ‘shop-floor control’, and have been addressed with top-down control that does not offer the robustness and agility required in modern competitive environments. The approach has been to reify parts and equipment as agents, and seek architectures that permit the overall shop schedule to emerge dynamically from their interaction, rather than being imposed top-down.
Mechanism of phthalate ester hydrolysis in water and in cyclodextrin mediated reactions (2003)

The kinetics of the hydrolysis of benzyl hydrogen phthalate 1 was studied at OH-concentration within 0.05 and 0.5 M. The reaction does not manifest appreciable intramolecular catalysis.The base catalyzed rate constant is about two orders of magnitude faster than the value predicted by the Brönsted plot defined by aryl hydrogen phthalate esters.In the presence of hydroxypropyl-βcyclodextrin (HPCD) at NaOH = 0.45 M and at pH= 12.8 the observed rate constant for the hydrolysis decreases as the HPCD concentration increases in a non-linear fashion.The kinetic results are interpreted in terms of the formation of an inclusion complex of the ionized substrate K CD A , with HPCD.In this complex the carboxylate group forms hydrogen bonds with the hydroxyl groups at the rim of the cyclodextrin cavity and the ionised group of the cyclodextrin is kept away from the reaction center due to electrostatic repulsion.
ChemInform Abstract: “Click” Reactions: A Versatile Toolbox for the Synthesis of Peptide‐Conjugates (2014)

Abstract Review: 237 refs.
Neutral sphingomyelinase as a target for drug design. (2001)

The sphingolipid ceramide is an important second messenger assumed to be involved in fundamental processes, including proliferation, differentiation and growth arrest, as well as the induction of apoptosis. Ceramide is generated in a ubiquitous and evolutionarily conserved signaling pathway called the sphingomyelin pathway, through the action of distinct isoforms of sphingomyelinases. An improved understanding of sphingomyelinase-dependent signaling may offer significant insights into the regulation of physiological and pathological processes and may finally provide novel strategies and new targets for pharmacological intervention (e.g., in inflammatory responses, neurodegenerative diseases and cancer). This article summarizes the current knowledge of the role of neutral sphingomyelinase (N-SMase) in cell signaling pathways, and its potential meaning, and demonstrates the opportunity of a specific inhibition of N-SMases as a novel therapeutic target.