gebhart/patrepeval huggingface dataset:
Insulin Resistance, Hyperinsulinemia, and Blood Pressure (1997)

In population surveys, blood pressure and plasma insulin concentration are related variables, but the association is confounded by age and obesity. Whether insulin resistance is independently associated with higher blood pressure in normal subjects is debated. We analyzed the database of the European Group for the Study of Insulin Resistance, made up of nondiabetic men and women from 20 centers, in whom insulin sensitivity was measured by the euglycemic insulin clamp. After excluding subjects aged > or =70 years, those with severe obesity (body mass index [BMI] >40 kg x m[-2]), and those with abnormal blood pressure values (> or =140/90 mm Hg), 333 cases (ages 18 to 70 years; BMI, 18.4 to 39.8 kg x m[-2]) were available for analysis. In univariate analysis, both systolic and diastolic blood pressures were inversely related to insulin sensitivity, with r values of 0.18 (P<.005) and 0.34 (P<.0001), respectively. In a multivariate model simultaneously accounting for sex, age, BMI, and fasting insulin, systolic and diastolic blood pressures were still inversely related to insulin sensitivity (partial r, 0.15 and 0.19; P<.01 for both). In this model, age was positively related to blood pressure levels independently of insulin sensitivity, whereas BMI was not. The predicted impact on blood pressure of a decrease in insulin sensitivity of 10 micromol x min(-1) x kg(-1) was +1.4 mm Hg, similar to that associated with a 10-year difference in age. Although insulin levels and insulin action were reciprocally interrelated, diastolic blood pressure varied as a simultaneous function of both. In normotensive, nondiabetic Europeans, insulin sensitivity and age are significant, mutually independent correlates of blood pressure, whereas body mass is not. The relation of blood pressure to both insulin action and circulating insulin levels is compatible with distinct influences on blood pressure by insulin resistance and compensatory hyperinsulinemia.
Mobilization and homing of peripheral blood progenitors is related to reversible downregulation of alpha4 beta1 integrin expression and function. (1998)

Despite the wide use of mobilized peripheral blood (PB) progenitor cells (PBPC) for clinical transplantation the mechanism(s) underlying their mobilization and subsequent engraftment are still unknown. We compared the adhesive phenotype of CD34(+) colony-forming cells (CFC) in bone marrow (BM) and PB of normal donors before and after administration of granulocyte colony-stimulating factor (G-CSF) for 5 d. G-CSF-mobilized PB CFC cells adhered significantly less to BM stroma, fibronectin, and to the alpha4 beta1 binding fibronectin peptide, CS1, because of decreased expression of the alpha4 integrin. Since incubation of BM CD34(+) cells for 4 d with G-CSF at concentrations found in serum of G-CSF- treated individuals did not affect alpha4-dependent adhesion, G-CSF may not be directly responsible for the decreased alpha4-mediated adhesion of PB CFC. Culture of G-CSF-mobilized PB CD34(+) cells with cytokines at concentrations found in BM stromal cultures upregulated alpha4 expression and restored adhesion of mobilized PB CFC to stroma, fibronectin, and CS1. Adhesion of cultured, mobilized PB CFC to stroma and CS1 could not be further upregulated by the beta1 activating antibody, 8A2. This indicates acquisition of a maximally activated alpha4 beta1 integrin once PB CFC have been removed from the in vivo mobilizing milieu. Thus, decreased alpha4 expression on CD34(+) CFC in PB may be responsible for the aberrant circulation of mobilized PB CD34(+) cells. Reexpression of a maximally activated alpha4 beta1 integrin on mobilized PB CFC removed from the mobilizing in vivo milieu may contribute to the early engraftment of mobilized PBPC.
Treatment evolution for metastatic castration‐resistant prostate cancer with recent introduction of novel agents: retrospective analysis of real‐world data (2015)

Despite increasing drug treatment options for metastatic castration-resistant prostate cancer (mCRPC) patients, real-world treatment data are lacking. We conducted retrospective analyses of commercial claims and electronic medical record (EMR) databases to understand how treatment patterns for mCRPC have changed in a US-based real-world population. Truven Health Analytics MarketScan(®) (2000-2013) and EMR (2004-2013) databases were used to identify patients with an index prostate cancer diagnosis (ICD-9 codes 185X or 233.4X) and prescription claims for an mCRPC drug (mitoxantrone, estramustine, docetaxel, sipuleucel-T, cabazitaxel, abiraterone acetate, enzalutamide, or radium-223). Regimen analyses for first line of therapy (LOT1), second line of therapy, and beyond were performed among cohorts based on year of first mCRPC drug usage. mCRPC drug usage and treatment duration were compared across cohorts and age groups within each cohort. The commercial claims cohort yielded 3437 evaluable patients. Most men (91%) commencing mCRPC treatment had docetaxel as LOT1 in 2010; this number had declined to 15% in 2013. In 2013, 67% and 9% of patients used abiraterone acetate and enzalutamide, respectively, as LOT1. Among both commercial claims and EMR cohorts, treatment pattern changes were most pronounced in men aged >80 years, and median treatment duration for some mCRPC drugs was shorter than expected based on available clinical trial information. These results demonstrate a shift in mCRPC treatments during the past 5 years, with greater use of newer noncytotoxic treatments than docetaxel. These real-world data aid in understanding the changing role of chemotherapy in the management of mCRPC.
Crystal structure of 4-[4-(dimethylamino)phenyl]-5-(2,4-dimethyl-1,3- thiazol-5-yl)-2,4-dihydro-3H-1,2,4-triazol-3-thione, C15H17N5S2 (2002)

C15H17N5S2, triclinio, PI (No. 2), a = 7.822(1) A,b = 8.355(1) , c = 13.925(2) A, a = 75.651(4), = 82.732(3), = 62.609(3), V = 782.7 3 , = 2, Rg(F) = 0.054, wR ief (F 1 ) = 0.155, T= 110 . compound (0.5 g) in acetonitrile-benzene ( 1:1,20 ml) left in room temperature for three days. The colorless crystals were Altered off, washed with cold acetonitrile-benzene (1:1,5 ml) and dried in vacuum over P4O10 (mp 498 K; yield 55%). Elemental analyses were consistent with the stiochiometry C15H17N5S2 (Found: C, 54.31%; H, 5.21%; N, 21.18%. Cale. : C, 54.36%; H, 5.17%; N, 21.13%). Melting points were measured on an Electrothermal 9100 apparatus and are uncorrected. Elemental analyses were performed using a Heraeus CHN-O-Rapid analyzer.
United States experience in environmental emergency planning and responses (2006)

This background paper reviews the development and key regulations of US environmental emergency planning and response, current main programs in their pollution/spill prevention, preparedness and response, systems and institutions carrying/implementing emergency planning and responses, and some on-going changes of their emergency response system after the September 11 terrorist attack.
Structure and Functions of Inhibitory and Excitatory Glycine Receptors (1999)

The strychnine-sensitive glycine receptor (GlyR) is a pentameric chloride channel protein that exists in several developmentally and regionally regulated isoforms in the CNS. These result from the differential expression of four genes encoding different variants (alpha 1-alpha 4) of the ligand-binding subunit of the GlyR. Their assembly with the structural beta subunit is governed by "assembly cassettes" within the extracellular domains of these proteins and creates chloride channels of distinct conductance properties. GlyR gating is potentiated by Zn2+, a metal ion co-released with different neurotransmitters. Site-directed mutagenesis has unraveled major determinants of agonist binding and Zn2+ potentiation. During development, glycine receptors mediate excitation that results in Ca2+ influx and neurotransmitter release. Ca2+ influx triggered by the activation of embryonic GlyRs is required for the synaptic localization of the GlyR and its anchoring protein gepyhrin. In the adult, mutations in GlyR-subunit genes result in motor disorders. The spastic and spasmodic phenotypes in mouse as well as human hereditary startle disease will be discussed.
An adaptive hybrid elasticity controller for cloud infrastructures (2012)

Cloud elasticity is the ability of the cloud infrastructure to rapidly change the amount of resources allocated to a service in order to meet the actual varying demands on the service while enforcing SLAs. In this paper, we focus on horizontal elasticity, the ability of the infrastructure to add or remove virtual machines allocated to a service deployed in the cloud. We model a cloud service using queuing theory. Using that model we build two adaptive proactive controllers that estimate the future load on a service. We explore the different possible scenarios for deploying a proactive elasticity controller coupled with a reactive elasticity controller in the cloud. Using simulation with workload traces from the FIFA world-cup web servers, we show that a hybrid controller that incorporates a reactive controller for scale up coupled with our proactive controllers for scale down decisions reduces SLA violations by a factor of 2 to 10 compared to a regression based controller or a completely reactive controller.
Telesoftware: Home Computing via Broadcast Teletext (1979)

Broadcast teletext, as operated by the broadcasting authoriities in the UK has been available as a public service since 1974. As well as being an efficient means of decoding and displaying textual data, it was soon realised that the standard teletext decoder already contained many of the components required for a home computer: it has a character-generator for visual- display; a page-store, and a very convenient numeric keypad for data-entry. With the addition of a few other components, the result is quite a powerful stand-alone computer right inside the TV set. By utilising the teletext system to broadcast programs for such a terminal, a user needs only to select the teletext pages containing a desired program; once this has been read in, it may be loaded and executed by the terminal microprocessor without the need for expensive-storage peripherals, telephone lines or special knowledge by the user.
Formation des formateurs en ligne : obstacles, rôles et compétences (2004)

An information and communication technology (ICT) cannot be used for teaching without bringing change to the organization. These changes affect the trainers who have a professional history, a mentality and practices developed over the years and in a specific work context. Technological changes can therefore destabilize a trainer's professional life. It is consequently essential to manage this change, to the extent that the success of projects in incorporating ICT into a training program are no longer dependent on technological capacity, but rather on the trainers' capacity to use their potential to change and improve the efficiency of the learning process. Accordingly, it is in the context of implementing an online train-the-trainer program that this article addresses the following questions: "What are the obstacles to change in a context of introducing ICT to a training setting?", "What are the main roles of an online trainer (or e-trainer)?", "What are the general skills that trainers need to develop to support learners in an online training context (synchronous and asynchronous)?"
Hypergeometric Functions by Direct Path Integration (1990)

The proverb, "the longest way round is the shortest way home," dating from the 17th century, applies as well to present-day computer programming. The technique of choice in many real-life computations is not necessarily the most efficient or elegant one, but may instead be the one that is quick to program and easy to check.
Synthesis of Poly(ethylene glycol)-block-poly(ethylenimine) Possessing an Acetal Group at the PEG End (2000)

A new linear block copolymer of poly(ethylene glycol) (PEG) and poly(ethylenimine) (PEI) possessing an acetal group at the PEG chain end was prepared by a heterotelechelic PEG macroinitiator technique. Heterotelechelic PEG with an acetal group at one end and a methanesulfonic group at the other end (acetal-PEG-SO2CH3) was synthesized by the anionic ring-opening polymerization of ethylene oxide (EO) initiated with potassium 3,3-diethoxypropanolate (PDP), followed by end-capping with methanesulfonyl chloride. Acetal-PEG-SO2CH3 was then used as a macroinitiator for the cationic ring-opening polymerization of 2-methyl-2-oxazoline (Oz) to form the block copolymer, acetal-PEG-POz. The block efficiency attained almost 100%, allowing to control the molecular weight of the POz segment by the initial monomer/initiator ratio. Alkaline hydrolysis of the repeating acetyl groups in the POz segment gave the completely deacylated block copolymer retaining the acetal group at the PEG chain end. The acetal-PEG-poly(ethylenimine) block copolymer thus obtained may have a potential utility as targetable DNA carrier in the field of gene delivery.
Economic Analysis of a Noninvasive Molecular Pathologic Assay for Pigmented Skin Lesions (2018)

The results of this analysis suggest that the PLA reduces cost and may improve the care of patients with primary pigmented skin lesions suggestive of melanoma.
PPARs, Obesity, and Inflammation (2007)

The worldwide prevalence of obesity and related metabolic disorders is rising rapidly, increasing the burden on our healthcare system. Obesity is often accompanied by excess fat storage in tissues other than adipose tissue, including liver and skeletal muscle, which may lead to local insulin resistance and may stimulate inflammation, as in steatohepatitis. In addition, obesity changes the morphology and composition of adipose tissue, leading to changes in protein production and secretion. Some of these secreted proteins, including several proinflammatory mediators, may be produced by macrophages resident in the adipose tissue. The changes in inflammatory status of adipose tissue and liver with obesity feed a growing recognition that obesity represents a state of chronic low-level inflammation. Various molecular mechanisms have been implicated in obesity-induced inflammation, some of which are modulated by the peroxisome proliferator-activated receptors (PPARs). PPARs are ligand-activated transcription factors involved in the regulation of numerous biological processes, including lipid and glucose metabolism, and overall energy homeostasis. Importantly, PPARs also modulate the inflammatory response, which makes them an interesting therapeutic target to mitigate obesity-induced inflammation and its consequences. This review will address the role of PPARs in obesity-induced inflammation specifically in adipose tissue, liver, and the vascular wall.
Liquid substitution: A versatile procedure for SEM specimen preparation of biological materials without drying or coating (1993)

Certain liquids with a very low vapour pressure, such as glycerol or triethylene glycol, can be used to infiltrate biological specimens so that they may be observed in the scanning electron microscope (SEM) without drying. The conductive properties of the fluids allow specimens to be examined either uncoated or with very thin coatings. The advantages of liquid substitution include the retention of lipids, waxes, loose particles, and surface contaminants. Since the procedure does not require expensive equipment, it offers an alternative to critical point drying or cryopreparation. For certain types of specimens, liquid substitution may represent the best preparation procedure. In addition, the fluids themselves may be imaged directly in the SEM, or indirectly by cathodoluminescence following labelling with fluorochromes.
Chlorinated Insecticides: Retrospect and Prospect (1977)

The story of the discovery of the chlorinated hydrocarbon derived insecticides is one of outstanding achievement which deserves due recognition. Indeed, the discovery within so few years of DDT, γ-HCH ( γ-BHC), the cyclodiene group and toxaphene, chlorinated insecticide types with distinct origins and synthetic principles, is truly remarkable. The continuing value of DDT and some other chlorinated compounds in Third World crop protection and human health programmes is widely recognised, whilst at the research level, chlorinated insecticides have already helped to elucidate the basic processes of insecticide metabolism which are a critical feature of insecticidal action. Many questions remain outstanding in regard to the mode of interaction of these compounds with insect nerve and its resistance to them; the answers to some of these questions may arise at any time as our knowledge progresses and may contribute to a better understanding of nerve function. For this Symposium on Pesticide
Gap Junction-Mediated Death of Retinal Neurons Is Connexin and Insult Specific: A Potential Target for Neuroprotection (2014)

Secondary cell death via gap junctions (GJs) plays a role in the propagation of neuronal loss under a number of degenerative disorders. Here, we examined the role of GJs in neuronal death in the retina, which has arguably the most diverse expression of GJs in the CNS. Initially, we induced apoptotic death by injecting single retinal ganglion cells and glia with cytochrome C and found that this resulted in the loss of neighboring cells to which they were coupled via GJs. We next found that pharmacological blockade of GJs eradicated nearly all amacrine cell loss and reduced retinal ganglion cell loss by ∼70% after induction of either excitotoxic or ischemic insult conditions. These data indicate that the GJ-mediated secondary cell death was responsible for the death of most cells. Whereas genetic deletion of the GJ subunit Cx36 increased cell survivability by ∼50% under excitotoxic condition, cell loss in Cx45 knock-out mouse retinas was similar to that seen in wild-type mice. In contrast, ablation of Cx45 reduced neuronal loss by ∼50% under ischemic insult, but ablation of Cx36 offered no protection. Immunolabeling of the connexins showed differential changes in protein expression consistent with their differing roles in propagating death signals under the two insults. These data indicate that secondary cell death is mediated by different cohorts of GJs dependent on the connexins they express and the type of initial insult. Our results suggest that targeting specific connexins offers a novel therapeutic strategy to reduce progressive cell loss under different neurodegenerative conditions.
Transient transformation of mammalian cells by MN protein, a tumor-associated cell adhesion molecule with carbonic anhydrase activity (1997)

The MN protein is associated with certain human carcinomas, but absent in most normal tissues. It is a transmembrane protein; its extracellular part contains a domain homologous with carbonic anhydrases (CAs) and a proteoglycan-like region. In the present study, we observed that cells (human CGL1 and mouse NIH3T3 cells) transfected with MN cDNA showed morphologic transformation, but reverted to normal phenotype after 4-5 weeks. This reversion was not due to the loss, silencing, or mutations of MN insert. We also found that MN protein exerted CA enzymatic activity, but this was not relevant for morphologic transformation of cells. MN is an adhesion protein, involved in cell-to-cell contacts, this probably could explain its role in tumorigenesis.
Residual noise compensation for robust speech recognition in nonstationary noise (2002)

We present a model-based noise compensation algorithm for robust speech recognition in nonstationary noisy environments. The effect of noise is split into a stationary part, compensated by parallel model combination, and a time varying residual. The evolution of residual noise parameters is represented by a set of state space models. The state space models are updated by Kalman prediction and the sequential maximum likelihood algorithm. Prediction of residual noise parameters from different mixtures are fused, and the fused noise parameters are used to modify the linearized likelihood score of each mixture. Noise compensation proceeds in parallel with recognition. Experimental results demonstrate that the proposed algorithm improves recognition performance in highly nonstationary environments, compared with parallel model combination alone.
L-Asparaginase and PEG Asparaginase— Past, Present, and Future (1993)

L-asparaginase is an enzyme which hydrolyses asparagine. Since the 1960s it has been known that some leukemic cells are deficient in asparagine synthetase and therefore cannot manufacture sufficient quantities of this essential amino acid to maintain cell viability. L-asparaginase is predominantly useful in acute lymphocytic leukemia (ALL) although responses have been noted in patients with acute myeloid leukemia, lymphoma, and rarely other tumors. L-asparaginase has been used in conjunction with methotrexate and ara-C in combination programs in leukemia. The major side-effect limiting the usefulness of L-asparaginase is allergic reactions. In addition, it is probable that neutralizing antibodies develop which shorten the half life of the drug so that the goal of depletion of plasma levels of asparagine cannot be attained or maintained. Polyethylene glycol (M.W. 5000) can be conjugated to L-asparaginase at sites not involving the active site of the enzyme. This enables free access of a small molecule, asparagine, to the active site of the enzyme but prevents uptake by the reticuloendothelial system, greatly decreasing the probability of developing antibodies against the asparaginase and prolongs the circulating half life of the drug. In a phase I/II study conducted at the M.D. Anderson Cancer Center, 37 heavily pretreated patients with refractory hematologic malignancy were treated. The age range from 15 to 73 years, median 49 years. Nineteen patients had ALL, 15 lymphoma, two myeloma, and one Hodgkin's disease. The dose levels of PEG L-asparaginase varied from 250 IU/m2 up to 8000 IU/m2. The pharmacokinetic profile demonstrated a monophasic half life consistent with a one compartment model with a single elimination phase.(ABSTRACT TRUNCATED AT 250 WORDS)
(S)-β3-Homolysine- and (S)-β3-Homoserine-Containingβ-Peptides: CD Spectra in Aqueous Solution (1998)

For further structural studies and for physiological investigations of β-peptides, it is necessary to have H2O-soluble derivatives. Thus, we have prepared β-hexa-, β-hepta-, and β-nonapeptides (1 – 6) with two, three, and seven side chains of lysine and serine. To detect possible π-π interactions, we also included the β-amino acid β2-HHop, resulting from homologation of so-called homophenylalanine (Hop) (5 and 6). The Fmoc-β2- and β3-amino-acid derivatives (11 – 14 and 19), and the corresponding β-peptides were prepared by methods previously described (solid-phase peptide coupling; HPLC-pure samples, Fig. 1). Circular-dichroism spectra (Fig. 2) indicate the presence of less pronounced secondary structures (especially of the lysine analogues with multiple positive charge) in H2O as compared to MeOH. The β3-heptapeptide (3) with two serine side chains is well soluble in H2O and exhibits the CD pattern typical of the 31-helical structure.