gebhart/patrepeval huggingface dataset:
[Evaluation of changes in hepatic energy metabolism during exercise by ketone body ratio in humans]. (1997)

Changes in the redox state of liver mitochondria were investigated by measuring the arterial ketone body ratio (acetoacetate/3-hydroxybutyrate: AKBR) in nine healthy volunteers (eight males and one female, mean age 38.4 +/- 5.0 years) during exercise. The correlation between the changes in AKBR and levels of various hormones controlling energy metabolism was also investigated. Subjects participated in symptom-limited exercise test using the ramping bicycle ergometer with expired gas analysis, blood pressure and 12 lead electrocardiogram monitoring. Anaerobic threshold by gas exchange parameters (ATge) was determined from the expired gas data with the v-slope method. AKBR, glucose, non-esterified fatty acid (NEFA) and lactate were measured in arterial plasma samples. Catecholamines (epinephrine, norepinephrine, dopamine), insulin, glucagon, antidiuretic hormone (ADH), growth hormone (GH), thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroxine (T4), human-atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were measured in venous plasma samples. AKBR was gradually decreased by exercise from the resting value of 1.82 +/- 0.20. AKBR reduction was potentiated after ATge to 0.93 +/- 0.18 (p < 0.01 vs rest) at peak exercise. AKBR was further decreased during recovery to the minimum value of 0.70 +/- 0.06 (p < 0.01) at 6 min in the recovery phase. AKBR then began to increase and reached 0.95 +/- 0.07 30 min after peak exercise. Epinephrine increased from 45.9 +/- 11.0 to 210 +/- 75 pg/ml (p < 0.01), norepinephrine increased from 348 +/- 52 to 1,277 +/- 111 pg/ml (p < 0.01), and dopamine increased from 13.0 +/- 1.9 to 25.0 +/- 2.5 pg/ml (p < 0.01) between rest and peak exercise, respectively. Insulin decreased from 22.0 +/- 3.5 to 14.2 +/- 2.1 pg/ml (p < 0.05). No significant change was observed in glucagon, ADH, GH, TSH, T3, T4, hANP or BNP. Glucose decreased from 124 +/- 9 to 84 +/- 8 mg/dl (p < 0.05), whereas NEFA increased from 94 +/- 10 to 190 +/- 66 mg/dl (p < 0.05). A negative correlation was observed between AKBR and lactate (r = -0.41, p < 0.001). These results indicate that hepatic adenosine triphosphate production is promoted as energy demand increases by exercise, and maximizes early in the recovery phase when hepatic energy demand is maximum due to active gluconeogenesis. The levels of catecholamines, insulin and lactate contribute to the control of liver energy metabolism.
General anesthetics can competitively interfere with sensitive membrane proteins. (1987)

It is not known whether proteins or lipids are the primary target of anesthetic action. The resolution of this problem is hampered by the fact that it is not possible to investigate the biological activity of integral membrane proteins in the absence of lipids. However, certain characteristics of membrane protein function inhibition by anesthetics cannot be explained on the basis of an indirect inhibition by disturbance of the lipid bilayer and, therefore, most likely are the result of a direct anesthetic-protein interaction. This is the case (i) when the anesthetics competitively interfere with the binding of an endogenous ligand to the membrane protein and (ii) when the size of the anesthetic molecule is of importance for the potency and/or mechanism of inhibition. The present study shows that this is true for a membrane transport system, the Na+/K+/Cl- cotransport in glial-type cells.
Two Rat Intestinal Alkaline Phosphatase Isoforms with Different Carboxyl-terminal Peptides Are Both Membrane-bound by a Glycan Phosphatidylinositol Linkage (1995)

Two cDNAs encode rat intestinal alkaline phosphatases having completely different carboxyl-terminal peptides; one is hydrophobic and fulfills the consensus requirements for glycan phosphatidylinositol linkage, and the other is neither hydrophobic nor hydrophilic, but contains a small amino acid domain (-NSASS-) just distal to a region of 17 threonine residues. Constructs were created using 80% of the amino-terminal portion of one alkaline phosphatase and the carboxyl-terminal portions of each of the isoforms. Both of the carboxyl-terminal peptides supported glycan phosphatidylinositol linkage as demonstrated by the following criteria: 1) plasma membrane targeting in transfected COS-1 cells, 2) release of transfected alkaline phosphatase by phosphatidylinositol-specific phospholipase C, 3) appearance of the trypanosome variable glycoprotein cross-reacting determinant after phospholipase C treatment, 4) ethanolamine incorporation into newly synthesized enzyme, 5) loss of phospholipase C release after mutation of the omega and omega + 2 positions in the putative linkage site, -NSA-, and 6) evidence of surface membrane localization by immunofluorescence using antibody against rat intestinal alkaline phosphatase. These data demonstrate that a predicted hydrophobic carboxyl-terminal sequence is not essential for glycan phosphatidylinositol linkage. Moreover, because both isomers are membrane-bound, the origin of soluble enzyme in the serum is likely to arise from the action of serum phosphatidylinositol-specific phospholipase C.
CD8+ T Cell–Independent Tumor Regression Induced by Fc-OX40L and Therapeutic Vaccination in a Mouse Model of Glioma (2013)

Despite the growing number of preclinical and clinical trials focused on immunotherapy for the treatment of malignant gliomas, the prognosis for this disease remains grim. Although some promising advances have been made, the immune response stimulated as a result of immunotherapeutic protocols has been inefficient at complete tumor elimination, primarily due to our lack of understanding of the necessary effector functions of the immune system. We previously demonstrated that a tumor lysate vaccine/Fc-OX40L therapy is capable of inducing enhanced survival and tumor elimination in the GL261 mouse glioma model. The following experiments were performed to determine the mechanism(s) of action of this therapy that elicits a potent antitumor immune response. The evidence subsequently outlined indicates a CD8(+) T cell-independent and CD4(+) T cell-, NK cell-, and B cell-dependent means of prolonged survival. CD8(+) T cell-independent tumor clearance is surprising considering the current focus of many cancer immunotherapy protocols. These results provide evidence for CD8(+) T cell-independent means of antitumor response and should lead to additional examination of the potential manipulation of this mechanism for future treatment strategies.
Hydrophobic amino acid in the i2 loop plays a key role in receptor-G protein coupling. (1993)

Signal transduction of the heptahelical G protein-coupled receptors (GPCRs) involves multiple receptor domains, but a universal consensus domain for coupling has not yet been defined. Alanine mutagenesis scanning was performed on the intracellular loops and the COOH tail of the human muscarinic cholinergic receptor (Hm1) to identify coupling domains. Stimulation of phosphatidylinositol (PI) turnover was determined after transfection of the alanine mutants into U293 human embryonic kidney cells. Alanine substitutions in four regions (loops i1, i2, and NH2 and COOH junctions of i3) impaired coupling efficiency by approximately 50% or more, but the strongest reduction (> 80%) resulted from alanine replacement of a single amino acid, leucine 131. This residue is located in the middle of the second intracellular loop (i2), within the highly conserved GPCR motif (DRYXXV(I)XXPL). The position equivalent to Leu-131 in Hm1 contains a bulky hydrophobic amino acid (L, I, V, M, or F) in nearly all cloned GPCRs. Substitution of Leu-131 with polar amino acids (aspartate and asparagine) also resulted in strongly defective coupling, whereas phenylalanine (found in the equivalent position in the beta 2 adrenoceptor) can replace leucine without losing PI coupling ability of Hm1. Alanine substitution of the corresponding amino acid in the Hm3 receptor (L174A) also inhibited agonist-stimulated PI turnover, while replacing Phe-139 with alanine in the beta 2 adrenoceptor suppressed stimulation of adenylyl cyclase. We propose that a bulky hydrophobic amino acid in the middle of the i2 loop serves as a general site relevant to G protein coupling, whereas coupling selectivity is governed by other receptor domains.
Services to support consistency in mobile collaborative applications (2002)

This paper describes the design of services to support consistency in collaborative mobile applications. The requirements for application level consistency in groupware applications are discussed and it is argued that existing consistency services for mobile environments fail to address these requirements because they assume infrequent (write) sharing of information. We present the design of a group execution service called G-QEX which is designed to support consistency in mobile applications and includes features necessary to cope with the fluctuations in QoS which characterise mobile environments.
Covalent Immobilization of Cellulose Layers onto Maleic Anhydride Copolymer Thin Films (2005)

Thin films of cellulose are advantageous for analytical studies in aqueous environments to investigate various factors determining the performance of cellulose-based products. However, the weak fixation of cellulose layers on common carrier materials often limits this approach. To address this problem, we suggest a novel maleic anhydride copolymer precoating technique which allows for the covalent attachment of cellulose thin films through esterification. Maleic anhydride copolymers were deposited and covalently bound onto planar, aminosilane-modified glass or silicon oxide surfaces. Cellulose was subsequently immobilized on top of the copolymer precoatings by spin coating from N-methylmorpholine-N-oxide/dimethyl sulfoxide solutions. The resulting cellulose films were thoroughly characterized with respect to layer thickness, morphology, chemical constitution, and electrical charging. The stability of the layers against shear stress was demonstrated in aqueous solutions and the covalent attachment of the cellulose to the copolymer films was proven by means of dissolution experiments followed by ellipsometry and high-resolution X-ray photoelectron spectroscopy.
Response : Zinc and Alzheimer's Disease (1995)

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Excited by Glutamate (2003)

Fine-tuning drugs to act on particular glutamate receptors could lead to treatments for anxiety, depression, addiction, and even schizophrenia.
The CD28 family: a T-cell rheostat for therapeutic control of T-cell activation (2004)

The CD28 family of receptors (CD28, cytotoxic T-lymphocyte-associated antigen 4 [CTLA-4], inducible costimulator [ICOS], program death-1 [PD-1], and B- and T-lymphocyte attenuator [BTLA]) plays a critical role in controlling the adaptive arm of the immune response. While considerable information is available regarding CD28 and CTLA-4, the function of the more recently discovered members of the CD28 family is less well understood. This review will highlight recent findings regarding the CD28 family with special emphasis on effects the CD28 family has on immunopathology, the discovery of costimulatory antibodies with superagonist function, and the status of clinical trials using various strategies to augment or block T-cell costimulation.
Introduction: Between States (2009)

This introductory chapter discusses the Transylvanian Question, or the struggle between Hungary and Romania for control of Transylvania. It suggests that the story of the Transylvanian Question offers a new way into a rather larger question—the history of the European idea—or how state leaders and national elites have interpreted what “Europe” means and what it does. An overview of the subsequent chapters is also presented.
Early pressure screens. (1999)

Publisher Summary This chapter reviews various studies using gynogenetic diploid zebrafish embryos produced by the early pressure (EP) method to screen for mutations affecting early embryogenesis and compares these screens with those of haploid embryos and of diparental diploids. Mutations affecting motoneuronal pathfinding and neural crest development are isolated using a screen in which mutations are identified in gynogenetic diploid embryos by whole mount immunohistochemistry as well as visible phenotypes. Comparison of the types of mutations thus isolated relative to those isolated in other screens reveals that screening F2 diploid embryos produced by EP compares favorably with screening F3 diploid embryos produced by normal matings, particularly when space is a consideration, although EP embryos are unsuitable for screening for some very specific features of embryogenesis, such as dorsovental patterning. The most important difference from other screens is that it focuses on particular phenotypes revealed by molecular markers for specific cell types. This approach is likely to have widespread application because it focuses on a single aspect of development, a strategy very important for isolation of specific mutations in other eukaryotes, and it reveals subtle mutations that may be cryptic and invisible without markers.
Mining Social Networks for Targeted Advertising (2006)

In this paper, we propose a data mining framework that utilizes the concept of social network for the targeted advertising of products. This approach discovers the cohesive subgroups from customer’s social network which is derived from customer’s interaction data. Based on the set of cohesive subgroups, we infer the probabilities of customer’s liking a product category from transaction records. Utilizing such information, we construct a targeted advertising system. We evaluate the proposed approach by using real email logs and library-circulation data. The experimental results show that our approach yields better quality of advertisement.
Prion Diseases and the BSE Crisis (1997)

Bovine spongiform encephalopathy (BSE) and human Creutzfeldt-Jakob disease (CJD) are among the most notable central nervous system degenerative disorders caused by prions. CJD may present as a sporadic, genetic, or infectious illness. Prions are transmissible particles that are devoid of nucleic acid and seem to be composed exclusively of a modified protein (PrPSc). The normal, cellular prion protein (PrPC) is converted into PrPSc through a posttranslational process during which it acquires a high beta-sheet content. It is thought that BSE is a result of cannibalism in which faulty industrial practices produced prion-contaminated feed for cattle. There is now considerable concern that bovine prions may have been passed to humans, resulting in a new form of CJD.
Nature of DNA sequences at the attachment regions of genes to the nuclear matrix (1993)

Matrix-attached regions (MARs) have been demonstrated to nest origins of replication and transcriptional enhancers. A set of 13 rules is proposed aimed at facilitating the classification of a DNA sequence as a matrix attachment region.(ABSTRACT TRUNCATED AT 250 WORDS)
Mycobacterium growth indicator tube testing in conjunction with the AccuProbe or the AMPLICOR-PCR assay for detecting and identifying mycobacteria from sputum samples (1997)

We have compared the ability of the Mycobacterium Growth Indicator Tube (MGIT) system, a new culture method with an oxygen-sensitive fluorescent sensor, to recover mycobacteria from sputum samples with the abilities of egg-based medium and the Septi-Chek AFB system. We have also assessed the clinical utility of the AccuProbe or the AMPLICOR-PCR assay to directly identify Mycobacterium tuberculosis complex and M. avium-M. intracellulare complex (MAC) from positive MGITs. From 382 sputum samples, 99 isolates of M. tuberculosis complex and 20 isolates of MAC were recovered. The MGIT system had the highest recovery rates for M. tuberculosis complex (97.0%) and MAC (100%), compared to recovery rates of 51.5 and 65.0%, respectively, with the egg-based medium and 81.8 and 85.0%, respectively, with the Septi-Chek AFB system. The shortest recovery times were also achieved with the MGIT system: 16.6 days for M. tuberculosis complex and 12.0 days for MAC, compared to 27.1 and 20.1 days, respectively, with the egg-based medium and 21.4 and 13.2 days, respectively, with the Septi-Chek AFB system. The AccuProbe identified 74 (77.1%) of the 96 M. tuberculosis complex-positive MGITs and 17 (85.0%) of the 20 MAC-positive vials. The AMPLICOR system correctly identified 94 (97.9%) of the 96 M. tuberculosis complex-positive MGITs and all 20 MAC-positive vials. Therefore, the MGIT system used in conjunction with the AMPLICOR system is a rapid and sensitive method for detecting and identifying M. tuberculosis complex and MAC isolates from sputum samples.
Synergistic Effects of Traumatic Head Injury and Apolipoprotein-epsilon4 in Patients With Alzheimer's Disease (1995)

Article abstract-The apolipoprotein-epsilon4 allele increases the risk of Alzheimer9s disease (AD), but cerebral deposition of beta-amyloid with age, a genetic mutation, or head injury may contribute to the pathogenesis of this disease. We examined the risks of AD associated with traumatic head injury and apolipoprotein-epsilon4 in 236 community-dwelling elderly persons. A 10-fold increase in the risk of AD was associated with both apolipoprotein-epsilon4 and a history of traumatic head injury, compared with a two-fold increase in risk with apolipoprotein-epsilon4 alone. Head injury in the absence of an apolipoprotein-epsilon4 allele did not increase risk. These data imply that the biological effects of head injury may increase the risk of AD, but only through a synergistic relationship with apolipoprotein-epsilon4. <b>NEUROLOGY 1995;45: </b> 555-557
Post-transcriptional Regulation of Vascular Endothelial Growth Factor by Hypoxia (1996)

The major control point for the hypoxic induction of the vascular endothelial growth factor (VEGF) gene is the regulation of the steady-state level of the mRNA. We previously demonstrated a discrepancy between the transcription rate and the steady-state mRNA level induced by hypoxia. This led us to examine the post-transcriptional regulation of VEGF expression. Actinomycin D experiments revealed that hypoxia increased VEGF mRNA half-life from 43 +/- 6 min to 106 +/- 9 min. Using an in vitro mRNA degradation assay, the half-life of VEGF mRNA 3'-untranslated region (UTR) transcripts were also found to be increased when incubated with hypoxic versus normoxic extracts. Both cis-regulatory elements involved in VEGF mRNA degradation under normoxic conditions and in increased stabilization under hypoxic conditions were mapped using this degradation assay. A hypoxia-induced protein(s) was found that bound to the sequences in the VEGF 3'-UTR which mediated increased stability in the degradation assay. Furthermore, genistein, a tyrosine kinase inhibitor, blocked the hypoxia-induced stabilization of VEGF 3'-UTR transcripts and inhibited hypoxia-induced protein binding to the VEGF 3'-UTR. These findings demonstrate a significant post-transcriptional component to the regulation of VEGF.
A longitudinal study of the hyaluronan level in the serum of patients with malignant mesothelioma under treatment. Hyaluronan as an indicator of progressive disease (1989)

The serum hyaluronan levels of 37 patients with malignant mesothelioma were followed during the course of treatment (high doses of methotrexate were given to 32 of these patients). The patients could be divided into the following two groups: (1) those with progressive disease (n = 17) or (2) those showing improvement during therapy (complete remission [n = 2], partial remission, or no change [n = 18]). On admission to the hospital, the patients with progressive disease showed significantly higher initial serum hyaluronan levels (median value, 250 micrograms/l) than those in the second group (median value, 97 micrograms/l) (P less than 0.005, Wilcoxon). Serum hyaluronan as a predictor of progressive disease has a sensitivity of 65% and a specificity of 85%. There was a significant increase in serum hyaluronan levels during treatment in patients with progression (P less than 0.01). In three patients with initially high levels there was a clear decrease in parallel with the reduction in tumor burden. In the remaining patients of the responder group, the values were constantly low. There was no significant correlation between the hyaluronan level and any other laboratory test performed on blood samples. Pleural fluid was removed for medical reasons from 13 patients. Neither the presence of pleural fluid nor its hyaluronan level were correlated to the progression of the disease. However, there was an interesting negative correlation between serum and pleural hyaluronan levels, indicating that an elevated serum hyaluronan level does not reflect high production in the pleural cavity.
Human PIR1 of the Protein-tyrosine Phosphatase Superfamily Has RNA 5′-Triphosphatase and Diphosphatase Activities (1999)

A human cDNA was isolated encoding a protein with significant sequence similarity (41% identity) to the BVP RNA 5'-phosphatase from the Autographa californica nuclear polyhedrosis virus. This protein is a member of the protein-tyrosine phosphatase (PTP) superfamily and is identical to PIR1, shown by Yuan et al. (Yuan, Y., Da-Ming, L., and Sun, H. (1998) J. Biol. Chem. 272, 20347-20353) to be a nuclear protein that can associate with RNA or ribonucleoprotein complexes. We demonstrate that PIR1 removes two phosphates from the 5'-triphosphate end of RNA, but not from mononucleotide triphosphates. The specific activity of PIR1 with RNA is several orders of magnitude greater than that with the best protein substrates examined, suggesting that RNA is its physiological substrate. A 120-amino acid segment C-terminal to the PTP domain is not required for RNA phosphatase activity. We propose that PIR1 and its closest homologs, which include the metazoan mRNA capping enzymes, constitute a subgroup of the PTP family that use RNA as a substrate.
Polyglycerol Hyperbranched Polyesters: Synthesis, Properties and Pharmaceutical and Biomedical Applications (2019)

In a century when environmental pollution is a major issue, polymers issued from bio-based monomers have gained important interest, as they are expected to be environment-friendly, and biocompatible, with non-toxic degradation products. In parallel, hyperbranched polymers have emerged as an easily accessible alternative to dendrimers with numerous potential applications. Glycerol (Gly) is a natural, low-cost, trifunctional monomer, with a production expected to grow significantly, and thus an excellent candidate for the synthesis of hyperbranched polyesters for pharmaceutical and biomedical applications. In the present article, we review the synthesis, properties, and applications of glycerol polyesters of aliphatic dicarboxylic acids (from succinic to sebacic acids) as well as the copolymers of glycerol or hyperbranched polyglycerol with poly(lactic acid) and poly(ε-caprolactone). Emphasis was given to summarize the synthetic procedures (monomer molar ratio, used catalysts, temperatures, etc.,) and their effect on the molecular weight, solubility, and thermal and mechanical properties of the prepared hyperbranched polymers. Their applications in pharmaceutical technology as drug carries and in biomedical applications focusing on regenerative medicine are highlighted.