gebhart/patrepeval huggingface dataset:
Identification of a Warfarin-sensitive protein component in a 200S rat liver microsomal fraction catalyzing vitamin K and vitamin K 2,3-epoxide reduction (1985)

A partially purified, 200S submicrosomal fraction exhibiting thiol-dependent vitamin K1 (vitamin K) and epoxide reductase activities has been isolated by partial solubilization of rat hepatic microsomes with sodium cholate and separation by centrifugation at 105 000 g into a discontinuous sucrose gradient. At pH 7.4, the rates of vitamin K and vitamin K 2,3-epoxide reduction per milligram of 200S fraction protein were equivalent and were 2.5-3.0 times faster than in microsomes. Reduction of vitamin K 2,3-epoxide occurred in a tightly coupled, two-step reaction initially to vitamin K and subsequently to vitamin K hydroquinone (vitamin KH2). Incorporation of glycerol or sucrose and of sodium cholate into reaction mixtures equivalently affected the rates of both vitamin K and vitamin K 2,3-epoxide reduction, but in the case of epoxide metabolism, the ratios of vitamin KH2/vitamin K were much lower, suggesting that the second reaction has been partially uncoupled from the first. A 14 000-17 000-dalton warfarin-sensitive protein (WSP) that participates in vitamin K and vitamin K 2,3-epoxide reduction in the 200S fraction was identified by incorporation of N-[3H]ethylmaleimide ([3H]NEM) into the catalytically active reduced form of one or more attached disulfides. Reduction of WSP with dithiothreitol was required for reaction with [3H]NEM, and the substrates vitamin K and vitamin K 2,3-epoxide and the inhibitor warfarin all effectively blocked the reaction. 2-Mercaptoethanol could not substitute for dithiothreitol.(ABSTRACT TRUNCATED AT 250 WORDS)
Plasma Apolipoprotein CI and CIII Levels Are Associated With Increased Plasma Triglyceride Levels and Decreased Fat Mass in Men With the Metabolic Syndrome (2008)

High concentrations of ApoCI and ApoCIII are associated with increased triglycerides and decreased visceral fat mass in men with the metabolic syndrome. These findings translate mouse studies into human pathophysiology.
Evidence for the negative cooperativity of the two active sites within bovine somatic angiotensin‐converting enzyme (2003)

The somatic isoform of angiotensin-converting enzyme (ACE) consists of two homologous domains (N- and C-domains), each bearing a catalytic site. We have used the two-domain ACE form and its individual domains to compare characteristics of different domains and to probe mutual functioning of the two active sites within a bovine ACE molecule. The substrate Cbz-Phe-His-Leu (N-carbobenzoxy-L-phenylalanyl-L-histidyl-L-leucine; from the panel of seven) was hydrolyzed faster by the N-domain, the substrates FA-Phe-Gly-Gly (N-(3-[2-furyl]acryloyl)-L-phenylalanyl-glycyl-glycine) and Hip-His-Leu (N-benzoyl-glycyl-L-histidyl-L-leucine) were hydrolyzed by both domains with equal rates, while other substrates were preferentially hydrolyzed by the C-domain. The inhibitor captopril ((2S)-1-(3-mercapto-2-methylpropionyl)-L-proline) bound to the N-domain more effectively than to the C-domain, whereas lisinopril ((S)-N(alpha)-(1-carboxy-3-phenylpropyl)-L-lysyl-L-proline) bound to equal extent with all ACE forms. However, active site titration with lisinopril assayed by hydrolysis of FA-Phe-Gly-Gly revealed that 1 mol of inhibitor/mol of enzyme abolished the activity of either two-domain or single-domain ACE forms, indicating that a single active site functions in bovine somatic ACE. Neither of the k(cat) values obtained for somatic enzyme was the sum of k(cat) values for individual domains, but in every case the value of the catalytic constant of the hydrolysis of the substrate by the two-domain ACE represented the mean quantity of the values of the corresponding catalytic constants obtained for single-domain forms. The results indicate that the two active sites within bovine somatic ACE exhibit strong negative cooperativity.
Human Hippocampal CA1 Involvement during Allocentric Encoding of Spatial Information (2009)

A central component of our ability to navigate an environment is the formation of a memory representation that is allocentric and thus independent of our starting point within that environment. Computational models and rodent electrophysiological recordings suggest a critical role for the CA1 subregion of the hippocampus in this type of coding; however, the hippocampal neural basis of spatial learning in humans remains unclear. We studied subjects learning virtual environments using high-resolution functional magnetic resonance imaging (1.6 mm x 1.6 mm in-plane) and computational unfolding to better visualize substructural changes in neural activity in the hippocampus. We show that the right posterior CA1 subregion is active and positively correlated with performance when subjects learn a spatial environment independent of starting point and direction. Altogether, our results demonstrate that the CA1 subregion is involved in our ability to learn a map-like representation of an environment.
Experimental allergic encephalomyelitis mediated by murine encephalitogenic T cell lines specific for myelin proteolipid apoprotein. (1987)

T cell lines specific for bovine myelin proteolipid apoprotein (PLP) were established from SJL/J mice. The line cells bore surface phenotypes of T helper/inducer cells (Lyt-1+, Lyt-2-, L3T4+) and responded well to bovine, rat, and guinea pig PLP but not to myelin basic protein. One line responded to major PLP, and another responded to both major PLP and DM-20, which are the two major intrinsic membrane proteins of the central nervous system (CNS) myelin. Intraperitoneal inoculation of 4 to 30 X 10(6) PLP-activated line cells followed by injection of pertussis vaccine induced acute inflammatory disease of the CNS, with typical clinical signs of EAE mostly in a week in recipient mice that had been treated with low-dose irradiation. Almost all animals recovered completely, and two of the 12 animals relapsed 42 or 75 days after inoculation. The lesions were restricted to the CNS and were characterized by perivascular and parenchymal infiltration of inflammatory cells, fibrin deposit, and demyelination. In the severe lesions, axons were also damaged. These observations suggest that PLP is a definite encephalitogen, and PLP-sensitized effector T cells induce inflammatory demyelination in the CNS.
Electric field mapping system using an optical-fiber-based electrooptic probe (2001)

A microwave electric-field mapping system based on electrooptic sampling has been developed using micromachined GaAs crystals mounted on gradient index lenses and single-mode optical fibers. The probes are able to detect three orthogonal polarizations of electric fields and, due to the flexibility and size of the optical fiber, can be positioned not only from the extreme near-field to the far-field regions of microwave and millimeter-wave structures, but also inside of enclosures such as waveguides and packages.
On the mechanism of penetration of ovicidal fungi through egg-shells of parasitic nematodes. Decomposition of chitinous and ascaroside layers. (1992)

The decomposition of egg-shells of Ascaris lumbricoides L. was studied microscopically using topochemical methods in a set of 32 strains of soil ovicidal fungi. It was found that even fungi displaying minimal chitinolytic activity in tests on purified chitin in vitro are able to dissolve chitin of egg-shells during the attack on live eggs. Fungi without any chitinolytic activity penetrate probably only the mechanically damaged eggs. None of the studied fungi was capable of degrading enzymatically the glycolipid (ascaroside) layer of the egg-shell which remained intact after digestion of all other components of the egg.
Validation of self reported smoking by serum cotinine measurement in a community-based study (2002)

Study objective: The validity of self reported smoking in population surveys remains an important question. An associated question is what would be the value of measuring serum cotinine concentrations in such surveys to obtain validated smoking data. Design: Cross sectional analysis of data on self reported smoking and serum cotinine among a random population sample of 5846 persons aged 25 to 64 years, who participated in the FINRISK-92 survey. Main results: Among self reported regular smokers, 97.2% of men and 94.9% of women had a cotinine concentration of 10 ng/ml or higher in serum. Of those participants who reported to have smoked at any time during their life but not during the previous month, 6.3% of men and 5.2% of women had a serum cotinine concentration of at least 10 ng/ml. Among never smokers 2.5% of men and 2.7% of women had detectable level of cotinine in their serum. The validity of self reporting was similar among subjects from different areas, ages, and socioeconomic groups. Conclusions: In a sample of the general population in Finland the validity of self reported smoking is high, and most of the few self reported non-smokers who had cotinine in their serum had only low or moderate levels.
Microfold-cell targeted surface engineered polymeric nanoparticles for oral immunization (2011)

Present work was envisaged to develop novel M-cell targeted polymeric particles that are capable of protecting the antigen from harsh gastric conditions. Ulex europaeus agglutinin (UEA-1) lectin was anchored for selective delivery of antigen to gut-associated lymphoid tissue (GALT). In the present investigation, chitosan nanoparticles were prepared by ionic gelation followed by antigen (bovine serum albumin, BSA) adsorption. Developed nanoparticles were further coated by UEA-1 lectin conjugated alginate and characterized for size, shape, zeta-potential, entrapment efficiency, and in vitro release. The immunological response of the developed system were performed in Balb/c mice and compared with aluminium hydroxide gel-based conventional vaccine. Results indicated that immunization with UEA-1 lectin conjugated alginate-coated particles induces efficient systemic as well as mucosal immune responses against BSA compared to other formulations. Aluminium-based vaccine dominated throughout the study, while failed in case of mucosal antibody. Additionally, IgG1 and IgG2a isotypes were determined to confirm the TH1/TH2 mixed immune response. The developed formulation exhibited superior systemic response along with dominating mucosal immunity. These data demonstrate the potential of UEA-alginate-coated nanoparticles as effective delivery system via oral route.
Paclitaxel and recombinant human granulocyte colony-stimulating factor as initial chemotherapy for metastatic breast cancer. (1993)

Taxol is highly active as initial chemotherapy for metastatic breast cancer. Administration of rhG-CSF reduced the incidence, depth, and duration of neutropenia, compared with published prior experience. Further studies of Taxol in breast cancer, including combinations with other active agents, are clearly warranted.
A novel subclass of thalidomide analogue with anti-solid tumor activity in which caspase-dependent apoptosis is associated with altered expression of bcl-2 family proteins. (2003)

Thalidomide is clinically useful in a number of cancers. Antitumor activity may be related to a number of known properties, including anti-tumor necrosis factor (TNF)-alpha and T-cell costimulatory and antiangiogenic activities. However, it may also involve direct antitumor effects. A series of second generation thalidomide analogues have been separated into two distinct groups of compounds, each with enhanced therapeutic potential, i.e., SelCIDs, which are phosphodiesterase (PDE) type IV inhibitors, and IMiDs, which have unknown mechanism(s) of action. We report here our efforts to determine direct antitumor effects of thalidomide and compounds from both groups. We found that one of the SelCID analogues (SelCID-3) was consistently effective at reducing tumor cell viability in a variety of solid tumor lines but had no effect on non-neoplastic cells. The antitumor activity was independent of known PDE4 inhibitory activity and did not involve cAMP elevation. Growth arrest was preceded by the early induction of G(2)-M cell cycle arrest, which led to caspase 3 mediated apoptosis. This was associated with increased expression of pro-apoptotic proteins and decreased expression of antiapoptotic bcl-2. Furthermore, extensive apoptosis in vivo was detected during SelCID-3-mediated inhibition of tumor growth in a murine xenotransplantation cancer model. Our results suggest that SelCID-3 represents a novel antitumor agent distinct from thalidomide and from previously characterized analogues with therapeutic potential against a range of solid tumors. This effect appears to be mediated via alterations in the expression of bcl-2 family proteins.
Modulation of the Affinity of Integrin α IIb β 3 (GPIIb-IIIa) by the Cytoplasmic Domain of α IIb (1991)

Intracellular signaling alters integrin adhesive functions in inflammation, immune responses, hemostasis, thrombosis, and retinal development. By truncating the cytoplasmic domain of alpha IIb, the affinity of integrin alpha IIb beta 3 for ligand was increased. Reconstitution with the cytoplasmic domain from integrin alpha 5 did not reverse the increased affinity. Thus, the cytoplasmic domain of the alpha subunit of GPIIb-IIIa controls ligand binding affinity, which suggests mechanisms for inside-out transmembrane signaling through integrins. These findings imply the existence of hitherto unappreciated hereditary and acquired thrombotic disorders in humans.
Theory and characterization of a top-thread coverstitched stretch sensor (2012)

One of the chief challenges of wearable sensing is adapting electronic components and sensors to the wearable environment. Electronic components are often rigid, bulky, and impermeable: factors that usually detract from wearing comfort. Here, we present a novel stretch sensor fabricated using the top thread of a standard industrial coverstitch machine. The machine is common in apparel production and offers the ability to easily fabricate custom-placed stretch sensors on textile and apparel products. The sensing properties of the stitch are enabled by a conductive thread which increases its electric resistance as the fabric is stretched, due to the geometry of the stitches. Our empirical analysis shows a sensor response in the order of 10 ohms, with almost linear behavior prior to saturation (when the stitch is fully stretched) for low-frequency extensions of 119% of initial sample length. An equivalent electrical model is presented for theoretical modeling of the sensor behavior.
Antiangiogenic Effect of Angiotensin II Type 2 Receptor in Ischemia-Induced Angiogenesis in Mice Hindlimb (2002)

This study examined the potential role of angiotensin type 2 (AT(2)) receptor on angiogenesis in a model of surgically induced hindlimb ischemia. Ischemia was produced by femoral artery ligature in both wild-type and AT(2) gene-deleted mice (Agtr2(-)/Y). After 28 days, angiogenesis was quantitated by microangiography, capillary density measurement, and laser Doppler perfusion imaging. Protein levels of vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), Bax, and Bcl-2 were determined by Western blot analysis in hindlimbs. The AT(2) mRNA level (assessed by semiquantitative RT-PCR) was increased in the ischemic hindlimb of wild-type mice. Angiographic vessel density and laser Doppler perfusion data showed significant improvement in ischemic/nonischemic leg ratio, 1.9- and 1.7-fold, respectively, in Agtr2(-)/Y mice compared with controls. In ischemic leg of Agtr2(-)/Y mice, revascularization was associated with an increase in the antiapoptotic protein content, Bcl-2 (211% of basal), and a decrease (60% of basal) in the number of cell death, determined by TUNEL method. Angiotensin II treatment (0.3 mg/kg per day) raised angiogenic score, blood perfusion, and both VEGF and eNOS protein content in ischemic leg of wild-type control but did not modulate the enhanced angiogenic response observed in untreated Agtr2(-)/Y mice. Finally, immunohistochemistry analysis revealed that VEGF was mainly localized to myocyte, whereas eNOS-positive staining was mainly observed in the capillary of ischemic leg of both wild-type and AT(2)-deficient mice. This study demonstrates for the first time that the AT(2) receptor subtype may negatively modulate ischemia-induced angiogenesis through an activation of the apoptotic process.
Cross-linked Smectites. IV. Preparation and Properties of Hydroxyaluminum-Pillared Ce- and La-Montmorillonites and Fluorinated NH 4 + -Montmorillonites (1985)

Abstract Reaction of hydroxy-Al oligocations with Ce 3+ - and La 3+ -exchanged montmorillonites, using 1.25, 1.60, or 2.0 mmole Al/g smectite, yielded partially pillared hydroxy-Al montmorillonite products containing a significant concentration of residual Ce 3+ or La 3+ . After heat treatment at 250°C these products showed high surface areas (∼340–500 m 2 /g) and high basal X-ray powder diffraction spacings (18.0–18.6 Å). Calcination at 400°–700°C resulted in lower surface areas of ∼200–450 m 2 /g and basal spacings of 16.3–18.3 Å, the values showing a gradual decrease with a decrease in the Al/smectite weight ratio and/or increase in the heat-treatment temperature. A major modification and improvement in the cross-linking procedure was achieved by fast aging (6–48 hr) of the hydroxy-Al oligomeric solution at 95°–100°C, instead of conventional aging for 2–3 weeks at 25°C. Fluorinated NH 4 + -montmorillonites, containing 0.4 to 2.1 wt. % F, were prepared by reaction of NH 4 + -montmorillonite at 60°C with 1.0 to 3.0 N aqueous solutions of NH 4 F. Interaction of the fluorinated montmorillonites with hydroxy-Al oligocations, using a ratio of 2.0 mmole Al/g smectite, yielded a series of cross-linked fluorinated montmorillonites with basal spacings of 17.9–18.0 Å and surface areas of 180–325 m 2 /g after heat treatment at 250°C. Calcination at 400°–500°C resulted in lower d(001) (16.6–17.7 Å) and surface-area values (140–300 m 2 /g). Increase in the fluorine content caused gradual decrease in both values. Transmission electron microscopy of pillared Ce-montmorillonite showed a highly oriented network of well-separated, parallel unit layers with an interlayer distance, Δd(001), of 9–10 Å. Calculated lateral (interpillar) distances were in good agreement with the pore-size distributions determined in independent adsorption studies.
Phosphoinositide 3-kinase: the key switch mechanism in insulin signalling (1998)

Insulin plays a key role in regulating a wide range of cellular processes. However, until recently little was known about the signalling pathways that are involved in linking the insulin receptor with downstream responses. It is now apparent that the activation of class 1a phosphoinositide 3-kinase (PI 3-kinase) is necessary and in some cases sufficient to elicit many of insulin's effects on glucose and lipid metabolism. The lipid products of PI 3-kinase act as both membrane anchors and allosteric regulators, serving to localize and activate downstream enzymes and their protein substrates. One of the major ways these lipid products of PI 3-kinase act in insulin signalling is by binding to pleckstrin homology (PH) domains of phosphoinositide-dependent protein kinase (PDK) and protein kinase B (PKB) and in the process regulating the phosphorylation of PKB by PDK. Using mechanisms such as this, PI 3-kinase is able to act as a molecular switch to regulate the activity of serine/threonine-specific kinase cascades important in mediating insulin's effects on endpoint responses.
Advances in the Study of Pyrrolo[2,1-c] [1,4]benzodiazepine (PBD) Antitumour Antibiotics (1993)

There is growing interest in agents, such as the pyrrolo[2,1-c][1,4]benzodiazepines (PBDs), that can recognize and bond to specific sequences of DNA. They have potential as gene regulators with possible therapeutic application in the treatmént of genetic disorders, including some cancers; as selective anti-infective agents; and as probes and tools for use in molecular biology (Dervan, 1986; Hurley and Boyd, 1988; Hurley, 1989; Thurston and Thompson, 1990). It is now approaching 30 years since the first PBD antitumour antibiotic, anthramycin, was discovered by Leimgruber (Leimgruber et al. 1965a, b). Since then, a total of nine naturally occurring PBDs have been reported, and over ten synthetic routes have been developed, leading to a variety of analogues (Thurston et al. 1992a). Biosynthetic pathways for the best-known natural products have been elucidated (Hurley and Speedie, 1981), and their mechanism of action has been studied by Kohn (Kohn, 1975) and more extensively by Hurley (Hurley and Needham-VanDevanter, 1986). It has now been established that the PBDs bind covalently in the minor groove of DNA to the exocyclic N2 of a guanine base via an acid-labile aminal bond. All these aspects of the PBDs have been reviewed in detail (Remers, 1988), and a number of general reviews have appeared (Thurston and Hurley, 1983; Hurley and Thurston, 1984). The objective of this chapter is to highlight recent advances in understanding the mechanism of formation of guanine-N2 adducts resulting from the application of high-field NMR, molecular modelling and DNA footprinting techniques during the last 10 years. Recent studies concerning the dynamics of DNA—adduct formation are also included. Possible correlations between drug structure, DNA-binding and biological activity are discussed, including the results of recent DNA-repair studies. Finally, examples of the application of this knowledge to the rational design of PBD analogues with modified DNA base-sequence selectivity and enhanced cytotoxicity are described.
Fading Relay Channels: Performance Limits and Space–Time Signal Design (2004)

Cooperative diversity is a transmission technique, where multiple terminals pool their resources to form a virtual antenna array that realizes spatial diversity gain in a distributed fashion. In this paper, we examine the basic building block of cooperative diversity systems, a simple fading relay channel where the source, destination, and relay terminals are each equipped with single antenna transceivers. We consider three different time-division multiple-access-based cooperative protocols that vary the degree of broadcasting and receive collision. The relay terminal operates in either the amplify-and-forward (AF) or decode-and-forward (DF) modes. For each protocol, we study the ergodic and outage capacity behavior (assuming Gaussian code books) under the AF and DF modes of relaying. We analyze the spatial diversity performance of the various protocols and find that full spatial diversity (second-order in this case) is achieved by certain protocols provided that appropriate power control is employed. Our analysis unifies previous results reported in the literature and establishes the superiority (both from a capacity, as well as a diversity point-of-view) of a new protocol proposed in this paper. The second part of the paper is devoted to (distributed) space-time code design for fading relay channels operating in the AF mode. We show that the corresponding code design criteria consist of the traditional rank and determinant criteria for the case of colocated antennas, as well as appropriate power control rules. Consequently space-time codes designed for the case of colocated multiantenna channels can be used to realize cooperative diversity provided that appropriate power control is employed.