gebhart/patrepeval huggingface dataset:
CoCl2, a Chemical Inducer of Hypoxia‐Inducible Factor‐1, and Hypoxia Reduce Apoptotic Cell Death in Hepatoma Cell Line HepG2 (2002)

HIF-1 (hypoxia-inducible factor-1) is the major transcription factor that is specifically activated during hypoxia. This transcription factor is composed of two subunits: HIF-1alpha and ARNT (aryl hydrocarbon receptor nuclear translocator). ARNT is constitutively expressed, whereas HIF-1alpha is targeted to proteasome degradation by ubiquitination during normoxia. In hypoxia, HIF-1alpha is stabilized and translocates to the nucleus, where it binds to ARNT. The active HIF-1 induces expression of various genes whose products play an adaptive role to the new conditions induced by hypoxia. Besides the role played by HIF-1 in the adaptation to hypoxia, recent data describe a possible role for HIF-1 in the modulation of apoptosis. According to some authors, hypoxia induces apoptosis. However, it has also been reported that hypoxia could protect cells against apoptotic cell death induced by various agents such as serum deprivation and incubation in the presence of chemotherapy agents. These contradictory data suggest that HIF-1 could display either a proapoptotic or an antiapoptotic role according to the conditions. In order to study how HIF-1 can modulate apoptosis, we studied whether hypoxia or cobalt chloride, a chemical inducer of HIF-1, could influence apoptosis induced by tert-butyl hydroperoxide (t-BHP), serum deprivation, or both in hepatoma cell line HepG2. HepG2 cells were incubated 8 hours under normoxia or hypoxia in the presence of t-BHP with or without CoCl2. CoCl2 reduced the apoptotic death of HepG2 cells induced by t-BHP and serum deprivation, as measured by DNA fragmentation. This effect was confirmed by measurement of the caspase activity. Moreover, hypoxia also prevented t-BHP- or serum deprivation-induced DNA fragmentation and caspase activation-however, to a lower extent than CoCl2. These different data suggest a possible antiapoptotic role of HIF-1. More experiments are needed to define if HIF-1 actually plays an active role in cell death protection and to determine the exact mechanism underlying this effect.
Garp as a therapeutic target for modulation of T regulatory cell function (2016)

Foxp3<sup>+</sup> T regulatory cells (Tregs) play critical roles in immune homeostasis primarily by suppressing many aspects of the immune response. Tregs uniquely express GARP on their cell surface and GARP functions as a delivery system for latent TGF-β. As Treg-derived TGF-β may mediate the suppressive functions of Tregs, GARP may represent a target to inhibit Treg suppression in cancer or augment suppression in autoimmunity. Areas covered: This article will focus on 1) the role of Treg-derived TGF-β in the suppressive activity of Treg, 2) the cellular and molecular regulation of expression of GARP on mouse and human Tregs, 3) the role of integrins in the activation of latent-TGF-β/GARP complex, 4) an overview of our present understanding of the function of the latent-TGF-β/GARP complex. Expert opinion: Two approaches are outlined for targeting the L-TGF-β1/GARP complex for therapeutic purposes. Tregs play a major role in suppressive effector T cell responses to tumors and TGF-β1 may be a major contributor to this process. One approach is to specifically block the production of active TGF-β1 from Tregs as an adjunct to tumor immunotherapy. The second approach in autoimmunity is to selectively enhance the production of TGF-β by Tregs at sites of chronic inflammation.
Heparin-copper biaffinity chromatography of fibroblast growth factors. (1988)

A novel method is described to separate and identify the various forms of fibroblast growth factor (FGF) based on their differential affinities for both heparin and copper.FGFs were extracted from bovine hypothalamus and purified by batchwise adsorption to heparin-Sepharose.The partially purified FGFs were then applied to an affinity column prepared by mixing equal portions of heparin-Sepharose and copper-Sepharose.The column was rinsed consecutively with the following four reagents: (i) 2 M NaCl, (ii) 0.6 M NaCl, (iii) 0.6 M NaCl plus 10 m M imidazole, and (iv) 0.6 M NaCl.FGFs were then eluted with a linear NaCl/imidazole gradient (from 0.6 M NaCl without imidazole to 2 M NaCl plus 10 m M imidazole).Fractions eluted from the column were analyzed by sodium dodecyl sulfate-gel electrophoresis with silver staining and electrophoretic immunoblot using site-specific antibodies against basic and acidic FGF.The results demonstrate that it is possible to resolve from hypothalamus at least two basic FGF species (with M, values of 19,000 and 18,000) and three acidic FGF species (with M, values of 18,000, 16,400, and 15,600).These findings indicate that heparin-copper biaffinity chromatography may have wide applicability in the study of the structure and activity of FGFs.
Study of the antidyskinetic effect of eltoprazine in animal models of levodopa‐induced dyskinesia (2013)

The serotonin (5-hydroxytryptamine [5HT]) system has recently emerged as an important player in the appearance of l-3,4-dihydroxyphenylalanine (levodopa [l-dopa])-induced dyskinesia in animal models of Parkinson's disease. In fact, dopamine released as a false transmitter from serotonin neurons appears to contribute to the pulsatile stimulation of dopamine receptors, leading to the appearance of the abnormal involuntary movements. Thus, drugs able to dampen the activity of serotonin neurons hold promise for the treatment of dyskinesia. The authors investigated the ability of the mixed 5-HT 1A/1B receptor agonist eltoprazine to counteract l-dopa-induced dyskinesia in 6-hydroxydopamine-lesioned rats and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated macaques. The data demonstrated that eltoprazine is extremely effective in suppressing dyskinesia in experimental models, although this effect was accompanied by a partial worsening of the therapeutic effect of l-dopa. Interestingly, eltoprazine was found to (synergistically) potentiate the antidyskinetic effect of amantadine. The current data indicated that eltoprazine is highly effective in counteracting dyskinesia in preclinical models. However, the partial worsening of the l-dopa effect observed after eltoprazine administration represents a concern; whether this side effect is due to a limitation of the animal models or to an intrinsic property of eltoprazine needs to be addressed in ongoing clinical trials. The data also suggest that the combination of low doses of eltoprazine with amantadine may represent a valid strategy to increase the antidyskinetic effect and reduce the eltoprazine-induced worsening of l-dopa therapeutic effects.
Optic disk neovascularization in a patient with cytomegalovirus retinitis associated with renal transplantation (2000)

Optic disk neovascularization may develop in the healing phase of CMV retinitis in renal transplant recipients.
Cleavage stage versus blastocyst stage embryo transfer in assisted reproductive technology (2007)

Background Recent advances in cell culture media have led to a shift in IVF practice from early cleavage embryo transfer to blastocyst stage transfer. The rationale for blastocyst culture is to improve both uterine and embryonic synchronicity and self selection of viable embryos thus resulting in higher implantation rates. Objectives To determine if blastocyst stage embryo transfers (ETs) affect live birth rate and associated outcomes compared with cleavage stage ETs and to investigate what factors may influence this. Search methods Cochrane Menstrual Disorders and Subfertility Group Specialised Register of controlled trials, Cochrane Controlled Trials Register (CENTRAL) (The Cochrane Library), MEDLINE, EMBASE and Bio extracts. The last search date was January 2007. Selection criteria Trials were included if they were randomised and compared the effectiveness of early cleavage versus blastocyst stage transfers. Data collection and analysis Of the 50 trials that were identified, 18 randomised controlled trials (RCTs) met the inclusion criteria and were reviewed. The primary outcomewas rate of live birth. Secondary outcomeswere rates per couple of clinical pregnancy,multiple pregnancy, high order pregnancy, miscarriage, failure to transfer embryos and cryopreservation. Quality assessment, data extraction and meta-analysis were performed following Cochrane guidelines.
Plant bZIP G‐box binding factors. (2001)

In this review we sum-up the knowledge about bZIP G-box binding factors (GBFs), which possess an N-terminal, proline-rich domain. The GBF has been one of the most extensively studied transcription factor family. Based on protein sequence homology with yeast and animal basic leucine-zipper (bZIP) transcription factors, bioinformatic studies have identified their main structural domains (proline-rich, basic and leucine-zipper), which have been further functionally characterized by in vitro and in vivo experiments. Recent reports have led to the discovery of other GBF-specific short amino-acid sequences that may take part in the regulation of gene expression by post-transcriptional modifications or interaction with other proteins such as bZIP enhancing factors or plant 14-3-3-like proteins. We identified a GBF region, called the 'multifunctional mosaic region', that may be implicated in cytoplasmic retention, translocation to the nucleus and regulation of transcription. We also identified many conserved protein motifs that suggest a modular structure for GBFs. At the whole plant level, GBFs have been shown to be involved in developmental and physiological processes in response to major cues such as light or hormones. Nevertheless, it remains difficult to assign a physiological role to a particular GBF protein modular structure. Finally, bringing together these different aspects of GBF studies we propose a model describing the puzzling transduction pathway involving GBFs from cytoplasmic events of signal transduction to the regulation of gene expression in the nucleus.
Time-resolved fluorescence imaging in biology and medicine (2002)

Fluorescence lifetime imaging is a rather new and effective tool that can be used to study complex biological samples, either at microscopic or macroscopic levels. The map of the fluorescence lifetime allows one to discriminate amongst different fluorophores and to achieve valuable insights into the behaviour of emitting molecules, leading to information like local pH, oxygen concentration in cells, etc. Moreover, the distribution in space of any fluorescent marker achievable with this technique can be exploited for diagnostic purposes in medicine. After a brief introduction on the motivations for applying fluorescence lifetime imaging in biology and medicine, the basic principles of this technique will be addressed. Then, the two possible implementations of fluorescence lifetime imaging (i.e. the frequency domain and the time domain methods) will be presented. For this purpose, special attention will be devoted to practical aspects of image acquisition and processing, especially for what concerns the time domain method. Then, the analysis of the state-of-the-art systems will include a brief discussion on new concepts that have recently been introduced in this research field. Finally, two interesting applications of fluorescence lifetime imaging will be presented. The former refers to skin tumour detection and has been successfully applied in a preliminary clinical trial, the latter regards DNA chips reading and has been tested only at laboratory level, yet it has produced promising results for its future implementation in commercial systems.
Discovery of PG545: A Highly Potent and Simultaneous Inhibitor of Angiogenesis, Tumor Growth, and Metastasis (2012)

Increasing the aglycone lipophilicity of a series of polysulfated oligosaccharide glycoside heparan sulfate (HS) mimetics via attachment of a steroid or long chain alkyl group resulted in compounds with significantly improved in vitro and ex vivo antiangiogenic activity. The compounds potently inhibited heparanase and HS-binding angiogenic growth factors and displayed improved antitumor and antimetastatic activity in vivo compared with the earlier series. Preliminary pharmacokinetic analyses also revealed significant increases in half-life following iv dosing, ultimately supporting less frequent dosing regimens in preclinical tumor models compared with other HS mimetics. The compounds also displayed only mild anticoagulant activity, a common side effect usually associated with HS mimetics. These efforts led to the identification of 3β-cholestanyl 2,3,4,6-tetra-O-sulfo-α-d-glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α-d-glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-α-d-glucopyranosyl-(1→4)-2,3,6-tri-O-sulfo-β-d-glucopyranoside, tridecasodium salt (PG545, 18) as a clinical candidate. Compound 18 was recently evaluated in a phase I clinical trial in cancer patients.
Negative symptoms, cognitive dysfunction, tardive akathisia and tardive dvskinesia (1996)

This study examined the relationship of neuropsychological deficits and negative symptoms with tardive akathisia in chronic schizophrenic patients. Consecutive volunteers (n = 100) were recruited from Community Health Centres with a DSM-III-R diagnosis of schizophrenic disorder, chronic and on stable medication. Subjects were subgrouped into tardive akathisia (TA), tardive dyskinesia (TD) and control groups using four sets of criteria. Detailed single examinations were performed using the following measures: sociodemographic, illness-related and treatment-related variables, Negative Symptom Rating Scale (NSRS), Abnormal Involuntary Movement Scale (AIMS), Rating Scale for Extrapyramidal Side-Effects (EPSE), Akathisia Rating Scale, Barnes Akathisia Rating Scale, and a brief neuropsychological test battery. Group comparisons and logistic regression analyses were performed in order to test the significance of findings. TA ratings showed a significant association with NSRS subscale scores, and with some neuropsychological test scores (Symbol Digits Modalities Test, and to a lesser extent Trail Making Test and Finger Tapping Test). TD scores showed a consistent association with age, and a less consistent association with gender, and their association with NSRS subscale scores and neuropsychological dysfunction was positive but less significant. Higher EPSE scores predicted TA and limb truncal (LT) dyskinesia. In conclusion, TA showed a more significant association with some clinical indices of organic brain dysfunction than the oral-lingual-buccal-facial dyskinetic syndrome. Prospective studies are necessary to determine whether organicity is a vulnerability factor for TA. Both our data and the published literature suggest that the movement disorder seen in TA and TD is but one feature of complex syndromes that include motor and cognitive features.
A Novel Ultrasonic Cased-Hole Imager for Enhanced Cement Evaluation (2005)

Abstract Current acoustic (sonic and ultrasonic) techniques for cement evaluation have proved to be limited in providing unambiguous answers to the zonal isolation issue. This is especially true in lightweight cements where they often fail to differentiate cement from mud. Also, as far as imaging of the cement sheath is concerned, ultrasonic pulse-echo tools fail to image beyond the cemented region adjacent to the casing, thus providing limited diagnosis of the annulus. A new ultrasonic imaging tool has been developed to address these limitations. The new imager combines the classical pulse-echo technique with a new ultrasonic technique that provides temporally compact echoes arising from propagation along the casing and also reflections at the cement-formation interface. Processing these signals yields unprecedented characterization of the cased hole environment in terms of the nature and acoustic velocity of the material filling the annulus between casing and formation, the material immediately behind casing, the position of the casing within the hole, and the geometrical shape of the hole. Different wells cemented with conventional and light cements were logged with the new experimental tool. The results demonstrate enhanced cement evaluation for both cement types and significant reduction in the uncertainty in making a squeeze or no-squeeze decision. Introduction Cement evaluation logging tools have been used successfully for many years to evaluate casing and cement conditions. These tools, which use sonic or ultrasonic1 techniques, are designed for conventional steel casing and cements. The sonic tools, commonly known as Cement Bond Log or CBL, operate at frequencies of about 20 kHz and measure the amplitude or the attenuation of a wave traveling along the casing. The wave loses energy mainly though shear coupling to the surrounding cement, so that well-bonded solid cement attenuates more quickly than a fluid. Due to the low frequency, the CBL logs made with these tools lack azimuthal resolution, which makes it difficult to distinguish channeling from poor cement properties.
Chemoprevention of tobacco-smoke lung carcinogenesis in mice after cessation of smoke exposure (2000)

Male strain A/J mice were exposed for 6 h per day, 5 days per week to a mixture of 89% cigarette sidestream smoke and 11% mainstream smoke. Total suspended particulate concentrations were 137 mg/m(3). In experiment 1, animals were exposed for 5 months to tobacco smoke and given a 4 month recovery period in air. Lung tumor multiplicity was 2.4 and incidence 89%. Animals exposed to filtered air had 1.0 tumor per lung (65% incidence). In animals kept for 5 months in smoke, removed into air and then fed a diet containing a mixture of myoinositol and dexamethasone, tumor multiplicity was 1.0 and incidence was 62%. These values were significantly (P < 0.01) lower than in animals exposed to smoke and identical to values seen in controls. In animals fed a diet containing 250 mg/kg each of phenethyl isothiocyanate and benzyl isothiocyanate during the entire 9 months, lung tumor multiplicity was 2.1 and incidence 96%, not significantly different from animals exposed to smoke and fed control diet. In experiment 2, animals were exposed for 5 months to smoke, followed by a 4 month recovery period in air and were fed during the entire period a diet containing either D-limonene or 1, 4-phenylenebis(methylene)selenoisocyanate (p-XSC). In animals exposed to tobacco smoke and fed control diet, lung tumor multiplicity was 2.8, whereas in the animals fed D-limonene it was 2. 6 and in the animals fed p-XSC it was 2.4. The differences to the controls were statistically not significant. It was concluded that myoinositol-dexamethasone successfully prevents the development of tobacco smoke-induced lung tumors even if administered when the animals have 'quit' smoking. On the other hand, agents otherwise shown to prevent lung tumor formation following administration of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone or benzo[a]pyrene were ineffective against tobacco smoke.
Differential Expression of Cardiac Biomarkers by Gender in Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction (2004)

In patients with UA/NSTEMI, there was a different pattern of presenting biomarkers. Men were more likely to have elevated creatine kinase-MB and troponins, whereas women were more likely to have elevated C-reactive protein and brain natriuretic peptide. This suggests that a multimarker approach may aid the initial risk assessment of UA/NSTEMI, especially in women. Further research is necessary to elucidate whether gender-related pathophysiological differences exist in presentation with acute coronary syndromes.
Micro RNA ‐27b suppresses tumor progression by regulating ARFGEF 1 and focal adhesion signaling (2015)

The non-receptor tyrosine kinase c-Src is frequently activated during progression of colon cancers. In this study, we found that among the c-Src-regulated microRNAs (miRNAs), miR-27b is also repressed by activation of K-Ras/H-Ras. Inhibitor studies suggested that the phosphatidylinositol 3-kinase pathway is involved in the repression of miR-27b. MicroRNA-27b was repressed in various colon cancer cell lines and tumor tissues. Re-expression of miR-27b in human colon cancer HCT116 cells caused morphological changes and suppressed tumor growth, cell adhesion, and invasion. We also identified ARFGEF1 and paxillin as novel targets of miR-27b, and found that miR-27b-mediated regulation of ARFGEF1 is crucial for controlling anchorage-independent growth, and that of paxillin is important for controlling cell adhesion and invasion. Re-expression of miR-27b suppressed the activation of c-Src induced by integrin-mediated cell adhesion, suggesting that repression of miR-27b may contribute to c-Src activation in cancer cells. These findings show that miR-27b functions as a tumor suppressor by controlling ARFGEF1 and the paxillin/c-Src circuit at focal adhesions.
Tri- and dicarboxylic acids, purines, pyrimidines and derivatives, coenzymes, inorganic compounds (1985)

Tri- and Dicarboxylic Acids. Purines, Pyrimidines, Nucleosides, Nucleotides, Coenzymes and Related Compounds. Nucleoside Diphosphate Sugars. Inorganic Compounds.
MPLS and next generation access networks (2002)

New IP-based technologies for supporting integrated voice and broadband data services over a single link are providing competitive carriers the opportunity to aggressively attack new markets. However, to deliver a comprehensive and competitively priced set of services, carriers must be able to manage QoS. MPLS provides the best alternative for managing QoS and class of service (CoS) for IP-based services. This article discusses how carriers can use MPLS to prioritize traffic and provision network bandwidth in order to offer integrated voice/data services, differentiated services and service level agreements.
Arid5a stabilizes OX40 mRNA in murine CD4+ T cells by recognizing a stem‐loop structure in its 3′UTR (2017)

AT-rich interactive domain-containing protein 5a (Arid5a) is an RNA-binding protein (RBP) required for autoimmunity via stabilization of interleukin-6 (Il6) and signal transducer and activator of transcription 3 (STAT3) mRNAs. However, the roles of Arid5a in Th17 cells and its association with autoimmunity remain unknown. Here, we show that the levels of Arid5a and OX40 are correlated in CD4<sup>+</sup> T cells under Th17 conditions in an IL-6-dependent manner. Lack of Arid5a in T cells reduced OX40 expression levels and repressed IL-17 production in response to OX40 ligation. Arid5a stabilized OX40 mRNA by recognizing the alternative decay element (ADE)-like stem-loop (SL) in the 3' untranslated region (3'UTR). Interestingly, Arid5a impaired the RNA-destabilizing functions of Regnase-1 and Roquin-1 on OX40 ADE-like SL. In EAE, Arid5a-deficient mice exhibited resistance to EAE, with reduced OX40 expression in CD4<sup>+</sup> T cells, and the number of CD4<sup>+</sup> CD45<sup>+</sup> T cells was decreased in CNS. Furthermore, ameliorated EAE was induced by adoptive transfer of Arid5a<sup>-/-</sup> encephalitogenic CD4<sup>+</sup> T cells expressing less OX40 mRNA and producing less IL-17. In conclusion, our findings indicate that the Arid5a/OX40 axis in CD4<sup>+</sup> T cells may have important implications in pathogenesis of autoimmune diseases such as EAE.
Transforming Regional Government Offices in England: a New Whitehall Agenda (2000)

The research upon which this chapter reports was entitled: Whitehall and the Reorganisation of regional offices in England. Research was undertaken over the period late 1994 to 1997. Little research had previously been undertaken on regional offices (Young 1982). The researchers have maintained an interest in more recent debates surrounding the government offices in England. As a result the chapter includes more recent findings as well as those arising from the ESRC project itself (Mawson 1997; Mawson and Spencer 1995a and b; Spencer and Mawson 1998).KeywordsCivil ServantRegional DirectorLabour GovernmentRegional CompetitivenessEnglish RegionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.