gebhart/patrepeval huggingface dataset:
Paraoxonase and Atherosclerosis (2001)

There is considerable evidence that the antioxidant activity of high density lipoprotein (HDL) is largely due to the paraoxonase-1 (PON1) located on it. Experiments with transgenic PON1 knockout mice indicate the potential for PON1 to protect against atherogenesis. This protective effect of HDL against low density lipoprotein (LDL) lipid peroxidation is maintained longer than is the protective effect of antioxidant vitamins and could thus be more important. There is evidence that the genetic polymorphisms of PON1 least able to protect LDL against lipid peroxidation are overrepresented in coronary heart disease, particularly in association with diabetes. However, these polymorphisms explain only part of the variation in serum PON1 activity; thus, a more critical test of the hypothesis is likely to be whether low serum PON1 activity is associated with coronary heart disease. Preliminary case-control evidence suggests that this is indeed the case and, thus, that the quest for dietary and pharmacological means of modifying serum PON1 activity may allow the oxidant model of atherosclerosis to be tested in clinical trials.
Assessing the Role of Human Recombinant Hyaluronidase in Gravity-Driven Subcutaneous Hydration: The INFUSE-LR Study (2007)

Background : Subcutaneous hydration has potential advantages over intravenous. Despite studies supporting the efficacy and safety of subcutaneous hydration it has not been studied extensively to date either with or without hyaluronidase. Objectives : To compare flow rate, tolerability, and safety of gravity-driven subcutaneous fluid administration with and without recombinant human hyaluronidase (rHuPH20) in healthy volunteers. Design : Randomized, double-blind, placebo-controlled, within-subject trial. Setting : Contract research organization. Participants : Fifty-four volunteers. Intervention : 24–gauge angiocatheters were placed subcutaneously in both upper arms. Each arm received rHuPH20 (150 U, 750 U, or 1500 U) or equal volume saline placebo. Immediately, 400 mL Lactated Ringer's (LR) solution was gravity-infused from a 100 cm height. In the pilot stage, 5 subjects also received a similar intravenous infusion. Measurements : Primary outcome was time to infuse 400 mL LR. Secondary outcomes included discomfort assessments, edema, arm circumference, time to recover to baseline arm circumference, subject and investigator global preference, and adverse events. Results : rHuPH20 150 U, 750 U, and 1500 U yielded mean flow rates of 383 ± 119 mL/hr, 518 ± 154 mL/hr, and 494 ± 136 mL/hr, respectively, compared to their respective placebo rates of 82 ± 30 mL/hr, 148 ± 57 mL/hr, and 124 ± 50 mL/hr. rHuPH20 was well tolerated. Conclusions : In volunteers, clinically relevant fluid volumes can be rapidly delivered subcutaneously with rHuPH20 in a well-tolerated manner without a pump. These findings suggest that this method of hydration could potentially replace intravenous infusions in many clinical settings; further studies with rHuPH20, in patients, are warranted.
Release of phospholipase A2 activity from rat vascular smooth muscle cells mediated by cAMP (1989)

Primary cultures of smooth muscle cells (SMC) derived from rat aorta release a phospholipase A2 activity into the culture medium. Phospholipase A2 activity was determined with [1-14C]oleate-labelled Escherichia coli as substrate. The enzyme has a neutral pH optimum and the activity is critically dependent on the free calcium concentration, with significant activity in the micromolar range of free calcium. Treatment of SMC with the beta agonist salbutamol, forskolin or cholera toxin, which all activate adenylate cyclase and increase intracellular cAMP concentration, increase the release of phospholipase A2 activity in a dose-dependent manner. Likewise, the addition of the membrane-permeable cAMP analogues, (Sp)-adenosine 3',5'-[thio]phosphate and N6,O-2'-dibutyryladenosine 3',5'-phosphate, enhance the release of phospholipase A2 activity from SMC in a dose-dependent manner. There is a lag period of about 4 h before a significant secretion of phospholipase A2 can be detected under basal, as well as under stimulated conditions. The forskolin analogue 1,9-dideoxyforskolin, which is inactive as a stimulator of adenylate cyclase, has no effect on phospholipase A2 secretion. Likewise, the potent vasoconstrictive peptide angiotensin II activates inositol phospholipid turnover in SMC, but has no effect on phospholipase A2 release. Pretreatment of SMC with actinomycin D or cycloheximide completely suppresses basal and cAMP-stimulated secretion of phospholipase A2 activity, thus demonstrating that transcription and protein synthesis are necessary for enzyme release.
GLP-1 stimulates secretion of macromolecules from airways and relaxes pulmonary artery (1993)

Recent data revealed the existence of specific receptors for glucagon-like peptide-1(7-36)amide (GLP-1) on rat lung membranes. Utilizing slide-mount autoradiography of fresh frozen lung tissue sections, we have localized binding sites for GLP-1 on mucous glands in the trachea and on vascular smooth muscle of the pulmonary artery. When tracheas were incubated in a modified Ussing chamber, the addition of GLP-1 to the submucosal side increased 35S-sulfate-labeled macromolecule secretion (191 +/- 12% above basal, P < 0.005). The optimal secretory response elicited by GLP-1 was approximately 23% of the maximal secretory response after a maximal acetylcholine stimulation. Other proglucagon-derived peptides such as glucagon, oxyntomodulin, and GLP-2 had no effect. In isolated rings of arteries, GLP-1 (10(-8) to 10(-5) M) induced a dose-dependent and time-reversible relaxation of preconstricted arteries. In a preparation with denuded epithelium, GLP-1 lost its effect. In conclusion, GLP-1 might represent another neuropeptide that acts as neurotransmitter of the peptidergic, nonadrenergic-noncholinergic nervous system that innervates the airways.
Multi-physics damage sensing in nano-engineered structural composites (2011)

Non-destructive evaluation techniques can offer viable diagnostic and prognostic routes to mitigating failures in engineered structures such as bridges, buildings and vehicles. However, existing techniques have significant drawbacks, including poor spatial resolution and limited in situ capabilities. We report here a novel approach where structural advanced composites containing electrically conductive aligned carbon nanotubes (CNTs) are ohmically heated via simple electrical contacts, and damage is visualized via thermographic imaging. Damage, in the form of cracks and other discontinuities, usefully increases resistance to both electrical and thermal transport in these materials, which enables tomographic full-field damage assessment in many cases. Characteristics of the technique include the ability for real-time measurement of the damage state during loading, low-power operation (e.g. 15 °C rise at 1 W), and beyond state-of-the-art spatial resolution for sensing damage in composites. The enhanced thermographic technique is a novel and practical approach for in situ monitoring to ascertain structural health and to prevent structural failures in engineered structures such as aerospace and automotive vehicles and wind turbine blades, among others.
Studies on Siloxanes. I. The Specific Volume and Viscosity in Relation to Temperature and Constitution (1946)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTStudies on Siloxanes. I. The Specific Volume and Viscosity in Relation to Temperature and ConstitutionCharles B. HurdCite this: J. Am. Chem. Soc. 1946, 68, 3, 364–370Publication Date (Print):March 1, 1946Publication History Published online1 May 2002Published inissue 1 March 1946https://pubs.acs.org/doi/10.1021/ja01207a005https://doi.org/10.1021/ja01207a005research-articleACS PublicationsRequest reuse permissionsArticle Views621Altmetric-Citations113LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
Hierarchical Docking of Databases of Multiple Ligand Conformations (2005)

Ligand flexibility is an important problem in molecular docking and virtual screening. To address this challenge, we investigate a hierarchical pre-organization of multiple conformations of small molecules. Such organization of pre-calculated conformations removes the exploration of ligand conformational space from the docking calculation and allows for concise representation of what can be thousands of conformations. The hierarchy also recognizes and prunes incompatible conformations early in the calculation, eliminating redundant calculations of fit. We investigate the method by docking the MDL Drug Data Report (MDDR), an annotated database of 100,000 molecules, into apo and holo forms of seven unrelated targets. This annotated database allows us to track the ranking of tens to hundreds of annotated ligands in each of the docking systems. The binding sites and database are prepared in an automated fashion in an attempt to remove some human bias from the calculations. Many thousands of explicit and implicit ligand conformations may be docked in calculations not much longer than required for single conformer docking. As long as internal energies are not considered, recombination with the hierarchy is additive as the number of degrees of freedom is increased. Molecules with even millions of conformations can be docked in a few minutes on a single desktop computer.
Radioiodinated Styrylbenzenes and Thioflavins as Probes for Amyloid Aggregates (2001)

We report for the first time that small molecule-based radiodiodinated ligands, showing selective binding to Abeta aggregates, cross the intact blood-brain barrier by simple diffusion. Four novel ligands showing preferential labeling of amyloid aggregates of Abeta(1-40) and Abeta(1-42) peptides, commonly associated with plaques in the brain of people with Alzheimer's disease (AD), were developed. Two 125I-labeled styrylbenzenes, (E,E)-1-iodo-2,5-bis(3-hydroxycarbonyl-4-hydroxy)styrylbenzene, 12 (ISB), and (E,E)-1-iodo-2,5-bis(3-hydroxycarbonyl-4-methoxy)styrylbenzene, 13 (IMSB), and two 125I-labeled thioflavins, 2-[4'-(dimethylamino)phenyl]-6-iodobenzothiazole, 18a (TZDM), and 2-[4'-(4''-methylpiperazin-1-yl)phenyl]-6-iodobenzothiazole, 18b (TZPI), were prepared at a high specific activity (2200 Ci/mmol). In vitro binding studies of these ligands showed excellent binding affinities with Kd values of 0.08, 0.13, 0.06, and 0.13 nM for aggregates of Abeta(1-40) and 0.15, 0.73, 0.14, and 0.15 nM for aggregates of Abeta(1-42), respectively. Interestingly, under a competitive-binding assaying condition, different binding sites on Abeta(1-40) and Abeta(1-42) aggregates, which are mutually exclusive, were observed for styrylbenzenes and thioflavins. Autoradiography studies of postmortem brain sections of a patient with Down's syndrome known to contain primarily Abeta(1-42) aggregates in the brain showed that both [(125)I]18a and [125I]18b labeled these brain sections, but [125I]13, selective for Abeta(1-40) aggregates, exhibited very low labeling of the comparable brain section. Biodistribution studies in normal mice after an iv injection showed that [125I]18a and [(125)I]18b exhibited excellent brain uptake and retention, the levels of which were much higher than those of [125I]12 and [125I]13. These findings strongly suggest that the new radioiodinated ligands, [125I]12 (ISB), [125I]13 (IMSB), [125I]18a (TZDM), and [125I]18b (TZPI), may be useful as biomarkers for studying Abeta(1-40) as well as Abeta(1-42) aggregates of amyloidogenesis in AD patients.
Th17 Cells Expressing KIR3DL2+ and Responsive to HLA-B27 Homodimers Are Increased in Ankylosing Spondylitis (2011)

CD4 Th cells producing the proinflammatory cytokine IL-17 (Th17) have been implicated in a number of inflammatory arthritides including the spondyloarthritides. Th17 development is promoted by IL-23. Ankylosing spondylitis, the most common spondyloarthritis (SpA), is genetically associated with both HLA-B27 (B27) and IL-23R polymorphisms; however, the link remains unexplained. We have previously shown that B27 can form H chain dimers (termed B27(2)), which, unlike classical HLA-B27, bind the killer-cell Ig-like receptor KIR3DL2. In this article, we show that B27(2)-expressing APCs stimulate the survival, proliferation, and IL-17 production of KIR3DL2(+) CD4 T cells. KIR3DL2(+) CD4 T cells are expanded and enriched for IL-17 production in the blood and synovial fluid of patients with SpA. Despite KIR3DL2(+) cells comprising a mean of just 15% of CD4 T in the peripheral blood of SpA patients, this subset accounted for 70% of the observed increase in Th17 numbers in SpA patients compared with control subjects. TCR-stimulated peripheral blood KIR3DL2(+) CD4 T cell lines from SpA patients secreted 4-fold more IL-17 than KIR3DL2(+) lines from controls or KIR3DL2(-) CD4 T cells. Strikingly, KIR3DL2(+) CD4 T cells account for the majority of peripheral blood CD4 T cell IL-23R expression and produce more IL-17 in the presence of IL-23. Our findings link HLA-B27 with IL-17 production and suggest new therapeutic strategies in ankylosing spondylitis/SpA.
Bidirectional RNA helicase activity of eucaryotic translation initiation factors 4A and 4F. (1990)

The mechanism of ribosome binding to eucaryotic mRNAs is not well understood, but it requires the participation of eucaryotic initiation factors eIF-4A, eIF-4B, and eIF-4F and the hydrolysis of ATP. Evidence has accumulated in support of a model in which these initiation factors function to unwind the 5'-proximal secondary structure in mRNA to facilitate ribosome binding. To obtain direct evidence for initiation factor-mediated RNA unwinding, we developed a simple assay to determine RNA helicase activity, and we show that eIF-4A or eIF-4F, in combination with eIF-4B, exhibits helicase activity. A striking and unprecedented feature of this activity is that it functions in a bidirectional manner. Thus, unwinding can occur either in the 5'-to-3' or 3'-to-5' direction. Unwinding in the 5'-to-3' direction by eIF-4F (the cap-binding protein complex), in conjunction with eIF-4B, was stimulated by the presence of the RNA 5' cap structure, whereas unwinding in the 3'-to-5' direction was completely cap independent. These results are discussed with respect to cap-dependent versus cap-independent mechanisms of ribosome binding to eucaryotic mRNAs.
Myosin as cofactor and substrate in fibrinolysis (1997)

Myosin accelerates plasminogen activation by tissue-type plasminogen activator (tPA), and is degraded extensively by plasmin. Myosin binds both tPA and plasminogen, and enhances activation of des1-77-plasminogen by tPA but not by urokinase-type plasminogen activator (uPA). Myosin decreases K(M) and increases k(cat) for des1-77-plasminogen activation by tPA, to yield catalytic efficiencies in excess of 8000 M-1 s-1. The effect of myosin is attributed to its C-terminal portion, the myosin rod. With a K(M) of 3 microM, myosin is a high-affinity substrate for plasmin. The findings indicate that myosin is a cofactor for plasminogen activation and a substrate for plasmin.
Mitochondria directly influence fertilisation outcome in the pig (2006)

The mitochondrion is explicitly involved in cytoplasmic regulation and is the cell's major generator of ATP. Our aim was to determine whether mitochondria alone could influence fertilisation outcome. In vitro, oocyte competence can be assessed through the presence of glucose-6-phosphate dehydrogenase (G6PD) as indicated by the dye, brilliant cresyl blue (BCB). Using porcine in vitro fertilisation (IVF), we have assessed oocyte maturation, cytoplasmic volume, fertilisation outcome, mitochondrial number as determined by mtDNA copy number, and whether mitochondria are uniformly distributed between blastomeres of each embryo. After staining with BCB, we observed a significant difference in cytoplasmic volume between BCB positive (BCB+) and BCB negative (BCB-) oocytes. There was also a significant difference in mtDNA copy number between fertilised and unfertilised oocytes and unequal mitochondrial segregation between blastomeres during early cleavage stages. Furthermore, we have supplemented BCB- oocytes with mitochondria from maternal relatives and observed a significant difference in fertilisation outcomes following both IVF and intracytoplasmic sperm injection (ICSI) between supplemented, sham-injected and non-treated BCB- oocytes. We have therefore demonstrated a relationship between oocyte maturity, cytoplasmic volume, and fertilisation outcome and mitochondrial content. These data suggest that mitochondrial number is important for fertilisation outcome and embryonic development. Furthermore, a mitochondrial pre-fertilisation threshold may ensure that, as mitochondria are diluted out during post-fertilisation cleavage, there are sufficient copies of mtDNA per blastomere to allow transmission of mtDNA to each cell of the post-implantation embryo after the initiation of mtDNA replication during the early postimplantation stages.
Cytotoxicity phase of diethylnitrosamine-induced hepatic neoplasia in medaka. (1990)

Adult Oryzias latipes were exposed to 50 mg of diethylnitrosamine per liter of water for 5 wk and then transferred to clean water for an additional 15 wk. Response of the liver during the first 6 wk were analyzed by enzyme histochemistry and by high-resolution light and transmission electron microscopy. After 1 wk, cytotoxicity was apparent at the light microscopic level by piecemeal necrosis and phagocytosis apoptosis by adjacent hepatocytes and resident macrophages. Spongiosis hepatis and inflammation, found as early as wk 3, were not widespread until wk 6. Glycogen depletion and multifocal increases in gamma-glutamyl transpeptidase were found as early as 3 wk. At 5 wk, macrophage infiltration and aggregation and hepatocyte lysosome proliferation were revealed by an increase in cells staining for acid phosphatase. In addition, a subpopulation of macrophages stained positively for glucose-6-phosphate dehydrogenase during wk 6. Other histochemical biomarkers (Mg2(+)-ATPase, DT-diaphorase, uridine diphosphoglucuronyl dehydrogenase) were not altered. Mitotic figures were rare for the entire 6-wk period. At the ultrastructural level, necrotic alterations of some hepatocytes were seen within 24 h. Within 48 h, an apparent reduction of hepatocyte glycogen and cell volume characterized the majority of hepatocytes; this was accompanied by an increase in interhepatocytic space and the length and complexity of the hepatocyte microvillous projections found in the space of Disse. Lipid vacuolar inclusions inhabited space previously occupied by glycogen. Margins of hepatocyte nuclei were irregular, and mitochondria were condensed and their shape altered so that crescentric and elongated profiles were abundant. Lysosomes and residual bodies were increased after 1 wk. The cytoplasmic processes delineating spongiotic lesions were identified as originating from Ito cells. After 4 wk, apparent proliferation of smooth endoplasmic reticulum and retention of transport lipid within its cisternae were seen. The toxic depletion of hepatocytes and the attendant altered cellular environment are discussed in relation to cell-to-cell interactions and the possible contribution of stromal and extracellular matrix changes to liver regeneration and neoplasia.
Mouse NIH 3T3 cells expressing human colony-stimulating factor 1 (CSF-1) receptors overgrow in serum-free medium containing human CSF-1 as their only growth factor. (1989)

Mouse NIH 3T3 cells expressing the human c-fms protooncogene encoding the receptor for colony-stimulating factor 1 (CSF-1) are able to proliferate in serum-free medium containing platelet-derived growth factor (PDGF), insulin, transferrin, and albumin as the only exogenous proteins. When PDGF and insulin were replaced by purified human recombinant CSF-1, the cells became spindle shaped and refractile, were no longer contact inhibited, and proliferated to high densities. Thus, transduction of the human c-fms gene into mouse fibroblasts can not only reprogram their growth factor requirements but can also induce ligand-dependent features of cell transformation. NIH 3T3 cells stably transformed by the feline v-fms oncogene or by a mutated, oncogenic human c-fms gene were able to proliferate in the absence of exogenous growth factors. A monoclonal antibody that prevents signal transduction by the human CSF-1 receptor inhibited the growth of cells transformed by the activated c-fms oncogene, confirming that CSF-1 receptor function was required to abrogate growth factor requirements and to maintain the transformed state.
A 2.4-GHz ISM-Band Sliding-IF Receiver With a 0.5-V Supply (2008)

<para xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> We report an ultra-low-voltage RF receiver for applications in the 2.4 GHz band, designed in a 90 nm CMOS technology. The sliding-IF receiver prototype includes an LNA, an image-reject <emphasis emphasistype="boldital">LC</emphasis> filter with single-ended to differential conversion, an RF mixer, an <emphasis emphasistype="boldital">LC</emphasis> IF filter, a quadrature IF mixer, RF and IF LO buffers, and an I/Q baseband section with a VGA and a low-pass channel-select filter in each path, all integrated on-chip. It has a programmable overall gain of 30 dB, noise figure of 18 dB, out-of-channel <formula formulatype="inline"><tex>${\hbox{IIP}}_{3}$</tex> </formula> of <formula formulatype="inline"><tex>${-}$</tex></formula>22 dBm. The 3.4 mm<formula formulatype="inline"><tex>$^{2}$</tex></formula> chip consumes 8.5 mW from a 0.5 V supply. </para>
Postoperative management of subthalamic nucleus stimulation for Parkinson's disease (2002)

The postoperative neurologic management of patients with deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson' s disease is a complex dynamic process that involves a progressive increase in stimulation intensity and a parallel decrease in antiparkinsonian medication while assessing the interactions of both treatments. Neurologists responsible for postoperative management of patients receiving STN DBS must have expert knowledge of the electroanatomy of the subthalamic area and be familiar with the medical treatment of motor and nonmotor symptoms, including the management of long-term complications of levodopa treatment. Neurosurgeons who perform DBS need to understand the principles that guide the postoperative adaptation of treatment. This article defines guidelines for setting stimulation parameters, adapting drugs and managing adverse effects.
Paraoxonase: biochemistry, genetics and relationship to plasma lipoproteins (1996)

Human serum paraoxonase is located on an HDL. It has the capacity to retard the accumulation of lipid peroxides in LDL under oxidizing conditions in vitro. Paraoxonase has a genetic polymorphism that results in a single amino acid substitution. Evidence indicates that both the serum concentration of paraoxonase and an individual's genotype are related to plasma lipid and lipoprotein concentrations, and possibly also to coronary heart disease, implicating paraoxonase in the development of atherosclerosis.