gebhart/patrepeval huggingface dataset:
Variable inhibition of cell-free translation by HIV–1 transcript leader sequences (1992)

The 5' ends of all human immunodeficiency virus type I (HIV-1) transcripts have the potential to coordinately regulate translation of HIV-1 mRNAs. Conflicting observations of the translational impact of these sequences in various systems stimulated these analyses of translation in reticulocyte lysates. We report a sensitive, rapid, quantitative, and inexpensive cell-free translation assay in which translational efficiency is monitored by enzymatic assay of the translation products. Using this assay and conventional radiolabeling assays, we demonstrate that the HIV-1 transcript leader inhibits downstream translation and that the stem-loop structure is required. Under our assay conditions, this inhibition occurs predominantly in cis and is not mediated by the 68 kD, interferon-induced, double-stranded RNA-activated kinase (p68). However, under other assay conditions the HIV-1 leader may activate p68 and inhibit translation in trans. We show that variation between individual preparations of cell-free extracts can dramatically alter the magnitude of the translational inhibition by the HIV-1 leader. Further, we provide evidence that a heat-labile factor is required for efficient translation of transcripts containing the HIV-1 leader. These observations provide a foundation for identifying factors required for translation of HIV-1 transcripts.
Adacolumn, an Adsorptive Carrier Based Granulocyte and MonocyteApheresis Device for the Treatment of Inflammatory and RefractoryDiseases Associated with Leukocytes (2003)

Apheresis has been recognized both economically and therapeutically as a novel approach for the treatment of inflammatory diseases, and certain others, which respond poorly to drug therapy. This report is about Adacolumn, an adsorptive carrier based granulocyte and monocyte apheresis device with a volume of 335 mL, filled with about 220 g of cellulose acetate beads of 2 mm diameter as the column adsorptive carriers. Pre- and post-column leukocyte counts have shown that the carriers adsorb about 65% of granulocytes, 55% of monocytes and 2% of lymphocytes from the blood in the column. Additionally, after apheresis, there is a marked decrease in inflammatory cytokines (TNF-alpha, IL-1beta, IL-6 and IL-8) produced by blood leukocytes, together with down-modulation of L-selectin and the chemokine receptor CXCR3. Adacolumn has been used to treat patients with rheumatoid arthritis, ulcerative colitis and HIV infection. Typical apheresis sessions have been 4-10, at a frequency of one or two sessions per week. Treatment of patients with Adacolumn has been associated with very promising efficacy and safety data. Accordingly, in Japan, Adacolumn has been approved by the Ministry of Health for the treatment of ulcerative colitia. Furthermore, Adacolumn met the required quality and safety standards for medical devices and received an EC certification (CE-mark) from TUV in 1999. However, although Adacolumn carriers are very efficient in depleting excess and activated granulocytes and monocytes/macrophages, the clinical efficacy associated with Adacolumn apheresis cannot be fully explained on the basis of reducing granulocytes and monocytes per se. Hence, a long lasting effect on inflammatory cytokine generation, chemokine activities or immunomodulation is likely, but the precise mechanisms involved are not fully understood yet.
Activity‐dependent regulation of energy metabolism by astrocytes: An update (2007)

Astrocytes play a critical role in the regulation of brain metabolic responses to activity. One detailed mechanism proposed to describe the role of astrocytes in some of these responses has come to be known as the astrocyte-neuron lactate shuttle hypothesis (ANLSH). Although controversial, the original concept of a coupling mechanism between neuronal activity and glucose utilization that involves an activation of aerobic glycolysis in astrocytes and lactate consumption by neurons provides a heuristically valid framework for experimental studies. In this context, it is necessary to provide a survey of recent developments and data pertaining to this model. Thus, here, we review very recent experimental evidence as well as theoretical arguments strongly supporting the original model and in some cases extending it. Aspects revisited include the existence of glutamate-induced glycolysis in astrocytes in vitro, ex vivo, and in vivo, lactate as a preferential oxidative substrate for neurons, and the notion of net lactate transfer between astrocytes and neurons in vivo. Inclusion of a role for glycogen in the ANLSH is discussed in the light of a possible extension of the astrocyte-neuron lactate shuttle (ANLS) concept rather than as a competing hypothesis. New perspectives offered by the application of this concept include a better understanding of the basis of signals used in functional brain imaging, a role for neuron-glia metabolic interactions in glucose sensing and diabetes, as well as novel strategies to develop therapies against neurodegenerative diseases based upon improving astrocyte-neuron coupled energetics.
Metformin, an AMPK activator, stimulates the phosphorylation of aquaporin 2 and urea transporter A1 in inner medullary collecting ducts (2016)

Nephrogenic diabetes insipidus (NDI) is characterized by production of very large quantities of dilute urine due to an inability of the kidney to respond to vasopressin. Congenital NDI results from mutations in the type 2 vasopressin receptor (V2R) in ∼90% of families. These patients do not have mutations in aquaporin-2 (AQP2) or urea transporter UT-A1 (UT-A1). We tested adenosine monophosphate kinase (AMPK) since it is known to phosphorylate another vasopressin-sensitive transporter, NKCC2 (Na-K-2Cl cotransporter). We found AMPK expressed in rat inner medulla (IM). AMPK directly phosphorylated AQP2 and UT-A1 in vitro. Metformin, an AMPK activator, increased phosphorylation of both AQP2 and UT-A1 in rat inner medullary collecting ducts (IMCDs). Metformin increased the apical plasma membrane accumulation of AQP2, but not UT-A1, in rat IM. Metformin increased both osmotic water permeability and urea permeability in perfused rat terminal IMCDs. These findings suggest that metformin increases osmotic water permeability by increasing AQP2 accumulation in the apical plasma membrane but increases urea permeability by activating UT-A1 already present in the membrane. Lastly, metformin increased urine osmolality in mice lacking a V2R, a mouse model of congenital NDI. We conclude that AMPK activation by metformin mimics many of the mechanisms by which vasopressin increases urine-concentrating ability. These findings suggest that metformin may be a novel therapeutic option for congenital NDI due to V2R mutations.
Influence of tribology on global energy consumption, costs and emissions (2017)

Calculations of the impact of friction and wear on energy consumption, economic expenditure, and CO2 emissions are presented on a global scale. This impact study covers the four main energy consuming sectors: transportation, manufacturing, power generation, and residential. Previously published four case studies on passenger cars, trucks and buses, paper machines and the mining industry were included in our detailed calculations as reference data in our current analyses. The following can be concluded: Fifty years ago, wear and wear-related failures were a major concern for UK industry and their mitigation was considered to be the major contributor to potential economic savings by as much as 95% in ten years by the development and deployment of new tribological solutions. The corresponding estimated savings are today still of the same orders but the calculated contribution to cost reduction is about 74% by friction reduction and to 26% from better wear protection. Overall, wear appears to be more critical than friction as it may result in catastrophic failures and operational breakdowns that can adversely impact productivity and hence cost.
Thermal aspects of high-average-power electrooptic switches (1987)

The average power of electrooptic switches is limited by thermal effects arising from linear optical absorption of the laser pulse. Under some circumstances, even a small optical absorption can cause the switch to be the average-power-limiting component of the laser system. These thermal effects can be managed by configuring the switch as a cooled thin plate. The thermal properties of thin plate switches are fully analyzed for general switch configurations, and the major average-power-limiting effects are quantified. The results are applied to KD*P and LiNbO <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</inf> switches. Both of these materials are found to be relatively poor average power switch materials. Electrooptic switches for future high-average-power applications will be configured in a thermally efficient manner, will probably require high excitation voltages, and will utilize new, mechanically strong materials.
Finite Element Analysis of Aluminum Honeycombs Subjected to Dynamic Indentation and Compression Loads (2016)

The mechanical behavior of aluminum hexagonal honeycombs subjected to out-of-plane dynamic indentation and compression loads has been investigated numerically using ANSYS/LS-DYNA in this paper. The finite element (FE) models have been verified by previous experimental results in terms of deformation pattern, stress-strain curve, and energy dissipation. The verified FE models have then been used in comprehensive numerical analysis of different aluminum honeycombs. Plateau stress, <i>σ<sub>pl</sub></i>, and dissipated energy (<i>E<sub>I</sub></i> for indentation and <i>E<sub>C</sub></i> for compression) have been calculated at different strain rates ranging from 10² to 10⁴ s<sup>-1</sup>. The effects of strain rate and <i>t/l</i> ratio on the plateau stress, dissipated energy, and tearing energy have been discussed. An empirical formula is proposed to describe the relationship between the tearing energy per unit fracture area, relative density, and strain rate for honeycombs. Moreover, it has been found that a generic formula can be used to describe the relationship between tearing energy per unit fracture area and relative density for both aluminum honeycombs and foams.
The δ <sub>C</sub> Isoform of CaMKII Is Activated in Cardiac Hypertrophy and Induces Dilated Cardiomyopathy and Heart Failure (2003)

Recent studies have demonstrated that transgenic (TG) expression of either Ca2+/calmodulin-dependent protein kinase IV (CaMKIV) or CaMKIIdeltaB, both of which localize to the nucleus, induces cardiac hypertrophy. However, CaMKIV is not present in heart, and cardiomyocytes express not only the nuclear CaMKIIdeltaB but also a cytoplasmic isoform, CaMKIIdeltaC. In the present study, we demonstrate that expression of the deltaC isoform of CaMKII is selectively increased and its phosphorylation elevated as early as 2 days and continuously for up to 7 days after pressure overload. To determine whether enhanced activity of this cytoplasmic deltaC isoform of CaMKII can lead to phosphorylation of Ca2+ regulatory proteins and induce hypertrophy, we generated TG mice that expressed the deltaC isoform of CaMKII. Immunocytochemical staining demonstrated that the expressed transgene is confined to the cytoplasm of cardiomyocytes isolated from these mice. These mice develop a dilated cardiomyopathy with up to a 65% decrease in fractional shortening and die prematurely. Isolated myocytes are enlarged and exhibit reduced contractility and altered Ca2+ handling. Phosphorylation of the ryanodine receptor (RyR) at a CaMKII site is increased even before development of heart failure, and CaMKII is found associated with the RyR in immunoprecipitates from the CaMKII TG mice. Phosphorylation of phospholamban is also increased specifically at the CaMKII but not at the PKA phosphorylation site. These findings are the first to demonstrate that CaMKIIdeltaC can mediate phosphorylation of Ca2+ regulatory proteins in vivo and provide evidence for the involvement of CaMKIIdeltaC activation in the pathogenesis of dilated cardiomyopathy and heart failure.
[DNA-duplexes with phosphoamide bond: interaction with restriction endonucleases EcoRII and SsoII]. (1987)

We studied the interaction of EcoRII and SsoII restriction endonucleases with synthetic DNA duplexes, containing 3'N----5'P and 3'P----5'N phosphoamide internucleotide bonds in one of the cleavage points. Enzymatic hydrolysis of the modified strand of the duplexes is blocked in all cases. The presence of phosphoamide bonds was found to reduce the rate of cleavage of the natural strand by EcoRII and to have no influence in case of SsoII. Properties of the EcoRII endonuclease complex with its substrate, containing non-cleavable 3'N----5'P internucleotide bonds in each cleavage point, were examined. In the presence of Mg2+ ions the equilibrium association constant of the enzyme-substrate complex is 3-fold reduced, and the dissociation rate constant of the complex is increased by 1.5 times.
A Review of the Existing Grading Schemes and a Proposal for a Modified Grading Scheme for Prostatic Lesions in TRAMP Mice (2011)

The transgenic adenocarcinoma of the mouse prostate (TRAMP) model is well established and offers several advantages for the study of chemopreventive agents, including its well-defined course of disease progression and high incidence of poorly differentiated carcinomas within a relatively short length of time. However, there is no consensus on the grading of prostatic lesions in these mice. In particular, agreement is lacking on the criteria for differentiating prostatic intraepithelial neoplasia (PIN) from well-differentiated adenocarcinoma, specifically as it relates to evidence of invasion. This differentiation is critical for evaluating the effects of putative chemopreventive agents on progression to neoplasia. Moreover, only one of the published grading schemes assigns numerical grades to prostatic lesions, which facilitate statistical analysis. Here, we review five currently available grading schemes and propose a refined scheme that provides a useful definition of invasion for the differentiation of PIN from well-differentiated adenocarcinoma and includes a numerical scoring system that accounts for both the most severe and most common histopathological lesions in each of the lobes of the prostate and their distributions. We expect that researchers will find this refined grading scheme to be useful for chemoprevention studies in TRAMP mice.
Human gastric carcinogenesis: a multistep and multifactorial process--First American Cancer Society Award Lecture on Cancer Epidemiology and Prevention. (1992)

Evidence from pathology and epidemiology studies has been provided for a human model of gastric carcinogenesis with the following sequential stages: chronic gastritis; atrophy; intestinal metaplasia; and dysplasia. The initial stages of gastritis and atrophy have been linked to excessive salt intake and infection with Helicobacter pylori. The intermediate stages have been associated with the ingestion of ascorbic acid and nitrate, determinants of intragastric nitrosation. The final stages have been linked with the supply of beta-carotene and with excessive salt intake. Nitrosating agents are candidate carcinogens and could originate in the gastric cavity or in the inflammatory infiltrate.
Amino acid metabolism during platelet storage for transfusion (1992)

Previous studies indicated that the concentration of ammonia rises during storage of platelet concentrates (PC) at 22 degrees C for transfusion and that fuels other than glucose are important for metabolism. Therefore, in the current study, we measured the concentrations of 17 plasma amino acids during PC storage; 16 of these either rose or were unchanged while the concentration of glutamine fell to zero by day 4. As the concentration of glutamine fell, the concentration of glutamate rose with a relationship suggesting that 65-75% of the glutamine was metabolized no further than glutamate. Phosphate-dependent glutaminase activity was present in platelets at 22.3 +/- 6.3 nmol/min/mg protein, a level similar to that seen in lymphocytes and macrophages. Leucodepletion studies excluded a significant contribution of contaminating leucocytes to these measurements. Thrombin stimulation did not increase the rate of glutamine metabolism. Analysis of the rates of glutamine metabolism suggests that it accounts for most of the ammonia produced during PC storage. However, it appears to be relatively insignificant as a metabolic fuel. The role of glutamine metabolism for platelets is uncertain. It may be a vestige of a pathway in the megakaryocyte. The ammonia which it produces may be deleterious for platelets and for patients with liver disease who receive PC infusions.
Variable phenotype of Alzheimer's disease with spastic paraparesis (2001)

A variant form of Alzheimer's disease (AD), in which spastic paraparesis (SP) precedes dementia, is characterised by large, noncored, weakly neuritic Abeta-amyloid plaques resembling cotton wool balls and is caused by genomic deletion of presenilin 1 exon 9. A pedigree with a 5.9 kb exon 9 deletion shows a phenotypic spectrum including subjects with typical AD or with SP and numerous cotton wool plaques. In SP subjects, dementia onset is delayed and modified. This phenotypic variation suggests that modifying factors are associated with exon 9 deletions.
Evolutionary Divergence of Platelet-Derived Growth Factor Alpha Receptor Signaling Mechanisms (2003)

Receptor tyrosine kinases (RTKs) direct diverse cellular and developmental responses by stimulating a relatively small number of overlapping signaling pathways. Specificity may be determined by RTK expression patterns or by differential activation of individual signaling pathways. To address this issue we generated knock-in mice in which the extracellular domain of the mouse platelet-derived growth factor alpha receptor (PDGFalphaR) is fused to the cytosolic domain of Drosophila Torso (alpha(Tor)) or the mouse fibroblast growth factor receptor 1 (alpha(FR)). alpha(Tor) homozygous embryos exhibit significant rescue of neural crest and angiogenesis defects normally found in PDGFalphaR-null embryos yet fail to rescue skeletal or extraembryonic defects. This phenotype was associated with the ability of alpha(Tor) to stimulate the mitogen-activated protein (MAP) kinase pathway to near wild-type levels but failure to completely activate other pathways, such as phosphatidylinositol (PI) 3-kinase. The alpha(FR) chimeric receptor fails to rescue any aspect of the PDGFalphaR-null phenotype. Instead, alpha(FR) expression leads to a gain-of-function phenotype highlighted by ectopic bone development. The alpha(FR) phenotype was associated with a failure to limit MAP kinase signaling and to engage significant PI3-kinase response. These results suggest that precise regulation of divergent downstream signaling pathways is critical for specification of RTK function.
Exclusive formation of cis-PhCH:CH(SiEt3) by addition of triethylsilane to phenylacetylene catalyzed by ruthenium complex [(Me2CH)3P]2RuHCl(CO) (1993)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTExclusive formation of cis-PhCH:CH(SiEt3) by addition of triethylsilane to phenylacetylene catalyzed by ruthenium complex [(Me2CH)3P]2RuHCl(CO)Miguel A. Esteruelas, Juana Herrero, and Luis A. OroCite this: Organometallics 1993, 12, 6, 2377–2379Publication Date (Print):June 1, 1993Publication History Published online1 May 2002Published inissue 1 June 1993https://pubs.acs.org/doi/10.1021/om00030a057https://doi.org/10.1021/om00030a057research-articleACS PublicationsRequest reuse permissionsArticle Views517Altmetric-Citations79LEARN 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
Role of multivesicular bodies and their components in the egress of enveloped RNA viruses (2008)

As an enveloped virus buds, the nascent viral capsid becomes wrapped in a plasma membrane-derived lipid envelope, and a membrane fission event is thus necessary to separate the virion from the host cell. This membrane fission event is well characterised in the case of enveloped RNA viruses, where it is promoted by late assembly domains (L-domains) present at the level of specific viral structural proteins. Research conducted over the past 10 years has demonstrated that L-domains represent docking sites for cellular proteins essential for the biogenesis of a cellular organelle, the multivesicular body (MVB). In this way, enveloped RNA viruses hijack the MVB components to the cellular site where the budding is executed. This review will focus on the cellular machinery exploited by enveloped RNA viruses in order to be released from infected cells. The role of ubiquitin and lipids in viral budding will also be discussed.
Security SLAs for Federated Cloud Services (2011)

The federated Cloud paradigm aims to provide flexible and reliable services composed of a mixture of internal and external mini-clouds, but this heterogeneous nature is also fuelling the security concerns of the customers. To allay the fears and deal with the threats associated with outsourcing data and applications to the Cloud, new methods for security assurance are urgently needed. This paper presents current work on Cloud Security Service Level Agreements and our approach on how to manage this in the context of hybrid clouds. The purpose is to facilitate rapid service composition and agreements based on the necessary security requirements and establish trust between the customer and provider. We also show how this can be applied on a realistic case study related to a hybrid Unified Communication service.
Selective targeting of M‐type potassium K<sub>v</sub>7.4 channels demonstrates their key role in the regulation of dopaminergic neuronal excitability and depression‐like behaviour (2017)

Because expression of K<sub>v</sub> 7.4 channels in the CNS is limited, selectively targeting this M channel subunit is likely to produce less on-target side effects than non-selective M channel modulators. Thus, K<sub>v</sub> 7.4 channels may offer alternative targets in treatment of depression.