gebhart/patrepeval huggingface dataset:
Prasugrel Compared With High Loading- and Maintenance-Dose Clopidogrel in Patients With Planned Percutaneous Coronary Intervention (2007)

Among patients undergoing cardiac catheterization with planned percutaneous coronary intervention, loading with 60 mg prasugrel resulted in greater platelet inhibition than a 600-mg clopidogrel loading dose. Maintenance therapy with prasugrel 10 mg/d resulted in a greater antiplatelet effect than 150 mg/d clopidogrel.
Nutritional problems and care of patients with far-advanced disease (1989)

Nutritional problems in far-advanced disease have complex and interrelated causes. This is particularly true with cancer patients, who may have systemic disease producing multiple physical and psychological effects and who require complex treatment. Some solutions can be found which, if tailored to the individual patient, can improve the quality of life for both relatives and patients.
Peroxisome Proliferator-activated Receptor γ Thiazolidinedione Agonists Increase Glucose Metabolism in Astrocytes (2003)

Activation of peroxisome proliferator-activated receptors (PPARs) can regulate brain physiology and provide protection in models of neurological disease; however, neither their exact targets nor mechanisms of action in brain are known. In many cells, PPAR gamma agonists increase glucose uptake and metabolism. Because astrocytes store glucose and provide lactate to neurons on demand, we tested effects of PPAR gamma agonists on astroglial glucose metabolism. Incubation of cortical astrocytes with the PPAR gamma thiazolidinedione (TZD) agonist pioglitazone (Pio) significantly increased glucose consumption in a time- and dose-dependent manner, with maximal increase of 36% observed after 4 h in 30 microm Pio. Pio increased 2-deoxy-glucose uptake because of increased flux through the type 1 glucose transporter. However, at this time point Pio did not increase type 1 glucose transporter expression, nor were its effects blocked by transcriptional or translational inhibitors. Pio also increased astrocyte lactate production as soon as 3 h after incubation. These effects were replicated by other TZDs; however, the order of efficacy (troglitazone > pioglitazone > rosiglitazone) suggests that effects were not mediated via PPAR gamma activation. TZDs increased astrocyte cAMP levels, and their glucose modifying effects were reduced by protein kinase A inhibitors. TZDs inhibited state III respiration in isolated brain mitochondria, whereas in astrocytes they caused mitochondrial membrane hyperpolarization. Pio protected astrocytes against hypoglycemia-induced cell death. Finally, glucose uptake was modified in brain sections prepared from Pio-fed rats. These results demonstrate that TZDs modify astrocyte metabolism and mitochondrial function, which could be beneficial in neurological conditions where glucose availability is reduced.
TnTIN and TnTAP: Mini-transposons for site-specific proteolysis in vivo (1997)

Tobacco etch virus (TEV) protease recognizes a 7-aa consensus sequence, Glu-Xaa-Xaa-Tyr-Xaa-Gln-Ser, where Xaa can be almost any amino acyl residue. Cleavage occurs between the conserved Gln and Ser residues. Because of its distinct specificity, TEV protease can be expressed in the cytoplasm without interfering with viability. Polypeptides that are not natural substrates of TEV protease are proteolyzed if they carry the appropriate cleavage site. Thus, this protease can be used to study target proteins in their natural environment in vivo, as well as in vitro. We describe two TnS-based mini-transposons that insert TEV protease cleavage sites at random into target proteins. TnTIN introduces TEV cleavage sites into cytoplasmic proteins. TnTAP facilitates the same operation for proteins localized to the bacterial cell envelope. By using two different target proteins, SecA and TolC, we show that such modified proteins can be cleaved in vivo and in vitro by TEV protease. Possible applications of the site-specific proteolysis approach are topological studies of soluble as well as of inner and outer membrane proteins, protein inactivation, insertion mutagenesis experiments, and protein tagging.
Improvement of the Closed Cranial Window Model in Rats by Intracarotid Infusion of Signalling Molecules Implicated in Migraine (2009)

Intravital microscopy on a closed cranial window allows one to measure change in the diameter of cranial blood vessels after intravenous (i.v.) administration of pharmacodynamic substances. Putative targets being pursued in migraine are large vasodilating peptide molecules such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase polypeptide (PACAP)-38. High i.v. doses are required to study their craniovascular pharmacology. Unfortunately, this leads to a drop in blood pressure (BP) that subsequently causes blood vessels to dilate by autoregulation. Hence it is difficult to decipher what effect is caused by direct receptor agonist interaction or contributed by autoregulation. In the present study we infused substances with an ingenious indwelling catheter in the common carotid artery in rats. Intracarotidly seven-, 12- and 17-fold lower doses of CGRP, PACAP-38 and capsaicin were required, respectively, compared with i.v. infusion to induce the same dilation in dural artery. Dilating intracarotid (i.c.) doses caused no or a minimal fall in BP, whereas equi-responsive i.v. doses caused a marked BP reduction. The CGRP blocking potential of olcegepant was amplified by > 20 times on i.c. infusion. Pial artery responses to CGRP did not change with i.c. infusion, demonstrating that dilations after i.v. CGRP are mediated by autoregulation rather than through specific receptors. We applied CGRP topically, which induced concentration-dependent dural vasodilation, but no effect on pial artery or on BP. In conclusion, this new approach offers an improvement of the existing model by allowing more accurate assessment of effects of pharmaca on the cranial vasculature without inducing significant systemic effects.
Airways Disease: Phenotyping Heterogeneity Using Measures of Airway Inflammation (2007)

: Despite asthma and chronic obstructive pulmonary disease being widely regarded as heterogeneous diseases, a consensus for an accurate system of classification has not been agreed. Recent studies have suggested that the recognition of subphenotypes of airway disease based on the pattern of airway inflammation may be particularly useful in increasing our understanding of the disease. The use of non-invasive markers of airway inflammation has suggested the presence of four distinct phenotypes: eosinophilic, neutrophilic, mixed inflammatory and paucigranulocytic asthma. Recent studies suggest that these subgroups may differ in their etiology, immunopathology and response to treatment. Importantly, novel treatment approaches targeted at specific patterns of airway inflammation are emerging, making an appreciation of subphenotypes particularly relevant. New developments in phenotyping inflammation and other facets of airway disease mean that we are entering an era where careful phenotyping will lead to targeted therapy.
From Ribosome to Riboswitch: Control of Gene Expression in Bacteria by RNA Structural Rearrangements (2006)

Structural elements in the 5' region of a bacterial mRNA can have major effects on expression of downstream coding sequences. Folding of the nascent RNA into the helix of an intrinsic transcriptional terminator results in premature termination of transcription and in failure to synthesize the full-length transcript. Structure in the translation initiation region of an mRNA blocks access of the translation initiation complex to the ribosome binding site, thereby preventing protein synthesis. RNA structures can also affect the stability of an RNA by altering sensitivity to ribonucleases. A wide variety of mechanisms have been uncovered in which changes in mRNA structure in response to a regulatory signal are used to modulate gene expression in bacteria. These systems allow the cell to recognize an impressive array of signals, and to monitor those signals in many different ways.
DOSE3D: EGS4 Monte Carlo code-based software for internal radionuclide dosimetry. (1999)

The agreement between DOSE3D and MIRDOSE3 results for most organs shows the validity of DOSE3D. The presented examples of calculation show that DOSE3D could provide additional data to dosimetric parameters given by MIRDOSE3 for a more patient-specific dosimetric approach.
Measurement of serum monocyte chemoattractant protein-1 and its clinical application for estimating the activity of granuloma formation in sarcoidosis. (1998)

These data suggest that MCP-1 may be expressed by the macrophages in the granuloma throughout the body, and that the measurement of serum MCP-1 levels may have clinical value as an indicator in estimating the activity of granuloma formation throughout the body in sarcoidosis.
Mutations in the leucine zipper of the human immunodeficiency virus type 1 transmembrane glycoprotein affect fusion and infectivity (1992)

Many retroviruses, including the human and simian immunodeficiency viruses, contain a leucine zipper-like repeat in a highly conserved region of the external domain of the transmembrane (TM) glycoprotein. This region has been postulated to play a role in stabilizing the oligomeric form of these molecules. To determine what role this region might play in envelope structure and function, several mutations were engineered into the middle isoleucine of the leucine zipper-like repeat of the human immunodeficiency virus type 1 (HIV-1) TM protein. A phenotypic analysis of these mutants demonstrated that conservative mutations (Ile to Val or Leu) did not block the ability of the viral glycoprotein to mediate cell-cell fusion or affect virus infectivity. In contrast, each of the other mutations, except for the Ile-to-Ala change, completely inhibited the ability of the glycoprotein to fuse HeLa-T4 cells and of mutant virions to infect H9 cells. The alanine mutation produced an intermediate phenotype in which both cell fusion and infectivity were significantly reduced. Thus, the biological activity of the glycoprotein titrates with the hydrophobicity of the residue in this position. None of the mutations affected the synthesis, oligomer formation, transport, or processing of the HIV glycoprotein complex. Although these results do not rule out a role for the leucine zipper region in glycoprotein oligomerization, they clearly point to a critical role for it in a post-CD4 binding step in HIV membrane fusion and virus entry.
Substrate Recognition and Catalysis by UCH-L1 (2006)

Deubiquitinating enzymes regulate essential cellular processes, and their dysregulation is implicated in multiple disease states. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) has garnered attention for its links with Parkinson's disease and cancer; however, the mechanism of action of this enzyme in cells remains poorly understood. In order to advance our understanding of UCH-L1 function, we have been developing small molecule modulators of the enzyme for use as tools to probe its role in cells. In support of these efforts, an investigation of the mechanism of UCH-L1 catalysis was previously reported. Here, we extend this mechanistic evaluation and examine substrate recognition by UCH-L1. We developed a panel of ubiquitin fusions to test the contribution of specific residues of ubiquitin to binding and catalysis by the enzyme, and determined the activation parameters of selected variants to gain additional mechanistic insight. Ubiquitin side chains critical for establishing the Michaelis complex and enabling catalysis were identified, and features of this complex that differ between UCH-L1 and a homologue, UCH-L3, were revealed. These data provide dramatic examples of differences in substrate specificity between these enzymes. The implications of our experiments with UCH-L1 for selective inhibitor design and the relationship to disease are discussed.
Microwave-Accelerated and Metal-Enhanced Fluorescence Myoglobin Detection on Silvered Surfaces: Potential Application to Myocardial Infarction Diagnosis (2006)

In this short paper, we describe a novel approach to both significantly accelerate and optically amplify fluorescence-based immunoassays. Our approach utilizes metal-enhanced fluorescence (MEF) to intrinsically optically amplify fluorescence signatures, which, when combined with the use of low-power microwaves to kinetically accelerate assays, provides for both ultrafast and ultrabright immunoassays. Surprisingly, the use of low-power microwaves and silver nanostructures provides for localized heating, concentrating the effect to the particles themselves as compared to the generic heating of the high dielectric assay fluid. We have subsequently applied our microwave-accelerated MEF approach to the detection of myoglobin, where its rapid quantification is paramount for the clinical assessment of an acute myocardial infarction.
Analyzing the dynamic behavior of downhole equipment during drilling (1984)

Advanced geothermal drilling systems will require a bottom hole assembly (BHA) which utilizes sophisticated electronic and mechanical equipment to accomplish faster, more trouble free, smarter drilling. The bit-drill string/formation interaction during drilling imposes complex, intermittent dynamic loading on the downhole equipment. A finite element computer code, GEODYN, is being developed to allow analysis of the structural response of the downhole equipment during drilling and to simulate the drilling phenomena (i.e. penetration, direction, etc.). Phase 1 GEODYN, completed early in 1984, provides the capability to model the dynamic response of a polycrystalline diamond compact (PDC) bit interacting with a non-homogeneous formation. Succeeding development phases will allow inclusion of stabilizers and, eventually, the entire drill string in addition to facilitating drill ahead simulation.
Parallel Synthesis and Biological Evaluation of 837 Analogues of Procaspase-Activating Compound 1 (PAC-1) (2011)

Procaspase-Activating Compound 1 (PAC-1) is an ortho-hydroxy N-acyl hydrazone that enhances the enzymatic activity of procaspase-3 in vitro and induces apoptosis in cancer cells. An analogue of PAC-1, called S-PAC-1, was evaluated in a veterinary clinical trial in pet dogs with lymphoma and found to have considerable potential as an anticancer agent. With the goal of identifying more potent compounds in this promising class of experimental therapeutics, a combinatorial library based on PAC-1 was created, and the compounds were evaluated for their ability to induce death of cancer cells in culture. For library construction, 31 hydrazides were condensed in parallel with 27 aldehydes to create 837 PAC-1 analogues, with an average purity of 91%. The compounds were evaluated for their ability to induce apoptosis in cancer cells, and through this work, six compounds were discovered to be substantially more potent than PAC-1 and S-PAC-1. These six hits were further evaluated for their ability to relieve zinc-mediated inhibition of procaspase-3 in vitro. In general, the newly identified hit compounds are two- to four-fold more potent than PAC-1 and S-PAC-1 in cell culture, and thus have promise as experimental therapeutics for treatment of the many cancers that have elevated expression levels of procaspase-3.
Improved Prony algorithm to identify multipath components (1987)

An improved Prony algorithm, code-named SVDP (singular value decomposition Prony), is proposed for identifying discrete multipath components. The new technique has been applied to data obtained from both laboratory and field experiments. The superiority of the algorithm in determining the number of rays present, and also in resolving close rays, is demonstrated.
Sortase A as a Novel Molecular “Stapler” for Sequence-Specific Protein Conjugation (2007)

The Sortase family of transpeptidase enzymes catalyzes sequence-specific ligation of proteins to the cell wall of Gram-positive bacteria. Here, we describe the application of recombinant Staphylococcus aureus Sortase A to attach a tagged model protein substrate (green fluorescent protein) to polystyrene beads chemically modified with either alkylamine or the in vivo Sortase A ligand, Gly-Gly-Gly, on their surfaces. Furthermore, we show that Sortase A can be used to sequence-specifically ligate eGFP to amino-terminated poly(ethylene glycol) and to generate protein oligomers and cyclized monomers using suitably tagged eGFP. We find that an alkylamine can substitute for the natural Gly3 substrate, which suggests the possibility of using the enzyme in materials applications. The highly specific and mild Sortase A-catalyzed reaction, based on small recognition tags unlikely to interfere with protein expression, thus represents a useful addition to the protein immobilization and modification tool kit.
Immunomodulatory Drugs Regulate HMGB1 Release from Activated Human Monocytes (2010)

Several HMGB1-specific antagonists have provided beneficial results in multiple models of inflammatory disease-preclinical trials including arthritis. Since no HMGB1-specific targeted therapy has yet reached the clinic, we have performed in vitro studies to investigate whether any of a selection of well-established antirheumatic drugs inhibit HMGB1 release as part of its mode of action. Freshly purified peripheral blood monocytes from healthy donors were stimulated in cultures with LPS and IFNγ to cause HMGB1 and TNF release detected in ELISPOT assays. Effects on the secretion were assessed in cultures supplemented with dexamethasone, cortisone, chloroquine, gold sodium thiomalate, methotrexate, colchicine, etanercept or anakinra. Pharmacologically relevant doses of dexamethasone, gold sodium thiomalate and chloroquine inhibited the extracellular release of HMGB1 in a dose-dependent mode. Immunostaining demonstrated that dexamethasone caused intracellular HMGB1 retention. No effects on HMGB1 secretion were observed in cultures with activated monocytes by any of the other studied agents. TNF production in LPS/IFNγ-activated monocytes was readily downregulated by dexamethasone and, to some extent, by chloroquine and etanercept. We conclude that dexamethasone, gold sodium thiomalate and chloroquine share a capacity to inhibit HMGB1 release from activated monocytes.
A real-time fault tolerant intra-body network (2003)

This paper designs an intra-body network (IBN) of nodes, consisting of small sensors and processing elements (SPEs) placed at different locations within the body and a personal digital assistant placed externally but in close proximity to the body. The sensors measure specific physiological attributes such as electrophysiological and biochemical changes in the myocardium (action potentials of cells), glucose level, blood viscosity etc. and forward them to the processing element. Communication protocols for configuration and data access protocols are proposed. The privacy of the IBN data, fault tolerance and real-time data acquisition are addressed.
[Current advances and expectations in tumor immunology]. (2001)

Natural killer (NK) cells and Interferon (IFN)-gamma have been implicated in immune surveillance against tumor. We demonstrated the critical role of perforin in NK cell-mediated cytotoxic activity and anti-tumor effect in IFN-gamma inducible IL-12. And, we recently reported that TRAIL is constitutively expressed on a substantial proportion of murine NK cells in the liver, and which is responsible for spontaneous cytotoxicity and the anti-metastatic activity against TRAIL-sensitive tumor cells along with perforin and Fas ligand. Interestingly, the TRAIL expression on liver NK cells appeared to be regulated by endogenously produced IFN-gamma. Consisting with this finding, IL-12 and NKT cell specific ligand, alpha-Galactosylceramide (alpha-GalCer), induced TRAIL-mediated cytotoxcity and anti-tumor effect, and which was mediated by TRAIL expressed on IFN-gamma-activated NK cells. Tumor necrosis factor(TNF)-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein belonging to the TNF family, which preferentially induces apoptotic cell death in various tumor cells in vitro. Preclinical studies in mice and nonhuman primates have shown that administration of recombinant soluble forms of TRAIL could suppress the growth of TRAIL-sensitive tumor xenografts with no apparent systemic toxicity. These studies suggested a potential utility of TRAIL as a cancer therapeutic, although TRAIL expression at protein levels and its physiological roles in tumor surveillance has remained unknown. Presented findings provide the first evidence for the physiological function of TRAIL as a tumor suppressor.
Synthesis of [3H]-labelled and unlabelled 2-deoxy-2-fluoro-myo-inositol and 1-deoxy-1-fluoro-scyllo-inositol for use in studies of the phosphoinositide cycle (1991)

2-Deoxy-2-fluoro-myo-inositol and 1-deoxy-1-fluoro-scyllo-inositol have been synthesized in their unlabelled and tritiated forms in order to study their potential as inhibitors of the phosphoinositide cycle.
Increased lymphoid MxA expression in acute asthma exacerbation in children (2001)

Flow cytometric assay of MxA protein expression in whole blood appears to be an easy and useful method to evaluate viral infections in acute asthma exacerbation.
Contribution of dihydrotestosterone to male sexual behaviour (1995)

Differences in concentrations of circulating dihydrotestosterone within the normal range may represent a major predictor of sexual activity in healthy young men.
Unique Alzheimer's Disease Paired Helical Filament Specific Epitopes Involve Double Phosphorylation at Specific Sites (1997)

Alzheimer's disease (AD) paired helical filaments (PHFs), building blocks of neurofibrillary tangles (NFTs) are composed of hyperphosphorylated forms of the microtubule-associated protein tau (i.e., PHF-tau). Currently, much effort is devoted to the development of diagnostic antibodies specific for PHF-tau since elevated tau levels are found in the cerebral spinal fluid of AD patients. To this end, we have mapped the epitopes of a large panel of monoclonal antibodies (mAbs) that recognized only phosphorylation dependent epitopes on PHF-tau. These mAbs include the PHF-tau specific mAb AT10 and 12 newly developed anti-PHF mAbs that recognize PHF-tau but not autopsy-derived normal adult tau on Western-blot and enzyme-linked immunosorbent assay (ELISA). Epitope analysis, together with data on known binding sites of previously published mAbs, revealed that Ser214, Thr231, and Ser396 are immunodominant phosphorylated amino acids in PHF-tau. Six of the 12 new mAbs recognized one of these three phosphorylated sites. With the exception of AT10 and PHF-27, all the mAbs also labeled fetal tau and biopsy-derived tau. Since mAbs AT10 and PHF-27 had little or no affinity for fetal tau and biopsy tau, they can be considered as the first "true" PHF-specific antibodies capable of distinguishing tau isoforms from normal versus AD subjects, suggesting a possible utility of these mAbs as diagnostic markers. Remarkably, the true PHF-specific antibodies recognized peptide sequences phosphorylated on more than one amino acid residue. The peptide recognition of mAb AT10 required the simultaneous phosphorylation of Thr212 and Ser214, and the peptide recognition of mAb PHF-27 was markedly increased when both the primary site Thr231 and the subsite Ser235 were phosphorylated. Since AT10 and PHF-27 are the only mAbs currently available that bind specifically to PHF-tau, these data suggest that double phosphorylation at Thr212/Ser214 and Thr231/Ser235 may be unique to PHF-tau. These data may facilitate the development of mAbs that can be used as specific diagnostic reagents for the detection of altered tau in cerebrospinal fluid of AD patients.
Tissue Kallikrein Is Essential for Invasive Capacity of Circulating Proangiogenic Cells (2010)

This study reveals new interactive components of the PACs invasive machinery, acting via protease- and kinin receptor-dependent mechanisms.