gebhart/patrepeval huggingface dataset:
Cerebrovascular Inflammation Following Subarachnoid Hemorrhage (2002)

Aneurysmal subarachnoid hemorrhage frequently results in complications including intracranial hypertension, rebleeding and vasospasm. The extravasated blood is responsible for a cascade of reactions involving release of various vasoactive and pro-inflammatory factors (several of which are purported to induce vasospasm) from blood and vascular components in the subarachnoid space. The authors review the available evidence linking these factors to the development of inflammatory lesions of the cerebral vasculature, emphasizing: 1) neurogenic inflammation due to massive release of sensory nerve neuropeptides; 2) hemoglobin from lysed erythrocytes, which creates functional lesions of endothelial and smooth muscle cells; 3) activity, expression and metabolites of lipoxygenases cyclooxygenases and nitric oxide synthases; 4) the possible role of endothelin-1 as a pro-inflammatory agent; 5) serotonin, histamine and bradykinin which are especially involved in blood-brain barrier disruption; 6) the prothrombotic and pro-inflammatory action of complement and thrombin towards endothelium; 7) the multiple actions of activated platelets, including platelet-derived growth factor production; 8) the presence of perivascular and intramural macrophages and granulocytes and their interaction with adhesion molecules; 9) the evolution, origins, and effects of pro-inflammatory cytokines, especially IL-1, TNF-alpha and IL-6. Human and animal studies on the use of anti-inflammatory agents in subarachnoid hemorrhage include superoxide and other radical scavengers, lipid peroxidation inhibitors, iron chelators, NSAIDs, glucocorticoids, and serine protease inhibitors. Many animal studies claim reduced vasospasm, but these effects are not always confirmed in human trials, where symptomatic vasospasm and outcome are the major endpoints. Despite recent work on penetrating vessel constriction, there is a paucity of studies on inflammatory markers in the microcirculation.
Powering of standby power supplies using flywheel energy storage (2002)

Beacon Power Corporation, a wholly-owned subsidiary of SatCon Technology Corporation, is developing the 20C1000 Series Cable/Telcom, 2.0 kWh flywheel energy system specifically designed as a "plug-for-plug" replacement for lead-acid batteries in standby power supply applications. This paper describes in detail the principles and practices of flywheel technology. In particular, the paper describes the system and its components, Beacon's spin test results, the field installation and maintenance procedures, and monitoring capabilities. A cost comparison with lead-acid batteries is also presented.
Observations on the Mechanism of Halogen-Bridge Cleavage by Unidentate Ligands in Square Planar Palladium and Platinum Complexes (1994)

Cyclo-palladation and - platination of nitrogen donor ligands lead to insoluble µ- chloro dimers which give µ- bromo and µ- iodo dimers on metathesis with the appropriate lithium halide. Addition of pyridine or 2,6-dimethylpyridine to the cyclopalladated dimers gives monomeric complexes with the halogen trans to the metal-carbon bond, whereas addition of 2,6-dimethylpyridine to the cycloplatinated complexes gives the isomer with the halogen cis to the metal-carbon bond. The results are discussed in terms of the mechanism of the bridge cleavage reaction.
Vascular Smooth Muscle Cell Heme Oxygenases Generate Guanylyl Cyclase–Stimulatory Carbon Monoxide (1995)

These results indicate that vascular SMCs have both constitutive and inducible HO activity, and they respond to specific stimuli to generate guanylyl cyclase-stimulatory CO in the same SMCs and in coincubated platelets.
Calcium hydroxylapatite (Radiesse): safety, techniques and pain reduction. (2009)

Although the cosmetic applications of injectable calcium hydroxylapatite (CaHA) commenced in the first years of the 21st century, only recently has the clinical use of this filler been optimized. This update will review safety, techniques, pain reduction by mixing with lidocaine and the use of CaHA in ethnic skin.
IL-10 Suppresses Chemokines, Inflammation, and Fibrosis in a Model of Chronic Renal Disease (2005)

IL-10 is a pluripotent cytokine that plays a pivotal role in the regulation of immune and inflammatory responses. Whereas short-term administration of IL-10 has shown benefit in acute glomerulonephritis, no studies have addressed the potential benefits of IL-10 in chronic renal disease. Chronically elevated blood levels of IL-10 in rats were achieved by administration of a recombinant adeno-associated virus serotype 1 IL-10 (rAAV1-IL-10) vector. Control rats were given a similar dose of rAAV1-GFP. Four weeks after injection, IL-10 levels in serum were measured by ELISA, and chronic renal disease was induced by a 5/6 nephrectomy (n = 6 in each group). Eight weeks later, rats were killed and renal tissue was obtained for RNA, protein, and immunohistochemical analysis. Serum levels of IL-10 were 12-fold greater in the rAAV1-IL-10 group by 4 wk after rAAV1-IL-10 administration (345 +/- 169 versus 28 +/- 15 pg/ml; P = 0.001), and levels were maintained throughout the experiment. rAAV1-IL-10 treatment resulted in less proteinuria (P < 0.05), lower serum creatinine (P < 0.05), and higher creatinine clearances (P < 0.01) compared with rAAV1-GFP-treated rats. Renal interstitial infiltration was significantly attenuated by rAAV1-IL-10 administration as assessed by numbers of CD4+, CD8+, monocyte-macrophages (ED-1+) and dendritic (OX-62+) cells (P < 0.05), and this correlated with reductions in the renal expression of monocyte (renal monocyte chemoattractant protein-1 mRNA and protein) and T cell (RANTES mRNA) chemokines. rAAV1-IL-10 administration decreased mRNA levels of IFN-gamma and IL-2 in the kidney. The reduction in inflammatory cells was associated with a significant reduction in glomerulosclerosis and interstitial fibrosis. It is concluded that IL-10 blocks inflammation and improves renal function in this model of chronic renal disease. The feasibility of long-term overexpression of a gene using the AAV serotype 1 vector system in a model of renal disease is also demonstrated.
Kidney transplants, antibodies and rejection: is C4d a magic marker? (2003)

The immunohistochemical detection of the complement degradation product C4d in renal allograft biopsies has gained considerable clinical interest in recent years. The accumulation of C4d along peritubular capillaries is generally regarded as a marker for an antibody-mediated allo-response and is associated with poor graft survival. The aim of this review is to discuss histological findings associated with the deposition of C4d. Emphasis is placed on diagnostic and therapeutic implications. Unanswered questions regarding C4d and graft injury are highlighted.
Molecular Dynamics Simulation Study of the Interaction of Trehalose with Lipid Membranes (2004)

The interactions of the cryoprotective agent trehalose with a lipid membrane made of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine at 323 K were studied by means of molecular dynamics simulations. It was observed that trehalose binds to the phospholipid headgroups with its main axis parallel to the membrane normal. Trehalose establishes hydrogen bonds with the carbonyl and phosphate groups and replaces water molecules from the lipid headgroup. Notably, the number of hydrogen bonds (HBs) that the membrane made with its environment was conserved after trehalose binding. The HBs between lipid and trehalose have a longer lifetime than those established between lipid and water. The binding of the sugar does not produce changes either in the lipid area or in the lipid order parameter. The effect of trehalose on the dipole potential is in agreement with experimental results. The contribution of the different components to the membrane dipole potential was analyzed. It was observed that the binding of trehalose produces changes in the different components and the sugar itself contributes to the surface potential due to the polarization of its hydroxyl in the interface.
Pharmacology of GABA (1982)

GABA-ergic systems are involved in all the main functions of the brain. In most brain regions impairment of this system produces epileptic activity. GABA-mediated inhibitory function can be enhanced by drugs of at least seven different types. They act on the metabolism or synaptic release of GABA, or its reuptake into neurones of glia, or on various components of the GABA receptor complex (GABA recognition site, "benzodiazepine" receptor or chloride ionophore). Among such compounds, those which act most specifically and potently on GABA receptors remain primarily research tools. Among compounds in clinical use, valproate, benzodiazepines, and anticonvulsant barbiturates al enhance GABA-mediated inhibition. In the future, new inhibitors of GABA uptake, new GABA agonists and potent inhibitors of GABA-transaminase are likely to become available. Trials of drugs enhancing GABA-ergic function have been made in a wide variety of neurological disorders. In most forms of epilepsy a therapeutic effect is evident. Real benefit from GABA therapies has not been demonstrated in the principal disorders of movement (Huntington's chorea, Parkinson's disease, dystonias), except in so far as they have a myoclonic or paroxysmal component. Among psychiatric disorders the acute symptoms of schizophrenia are exacerbated by enhanced GABA-ergic function. Abstinence syndromes (alcohol, barbiturate or narcotic withdrawal) are ameliorated by drugs enhancing GABA-ergic function, and there is some evidence for a beneficial action in anxiety states and mania. Attempts to relate the molecular neurobiology of GABA with clinical pharmacology are of very recent origin. Improved understanding of the variety of GABA receptor mechanisms will provide the key to the more selective pharmacological manipulations that are required for therapeutic success.
Aortic stiffness: pathophysiology, clinical implications, and approach to treatment (2014)

Aortic stiffness is a hallmark of aging, and classic cardiovascular risk factors play a role in accelerating this process. Current changes in medicine, which focus on preventive care, have led to a growing interest in noninvasive evaluation of aortic stiffness. Aortic stiffness has emerged as a good tool for further risk stratification because it has been linked to increased risk of atherosclerotic heart disease, myocardial infarction, heart failure, and stroke. This has led to the invention and validation of multiple methods to measure aortic stiffness. Pulse wave velocity is emerging as the gold standard for evaluation of aortic stiffness. This review focuses on the pathophysiology involved in aortic stiffness, methods available for evaluation of aortic stiffness, the importance of central pressure as a predictor of future cardiovascular events, and therapies that affect aortic stiffness.
Nitric Oxide Acutely Inhibits Neuronal Energy Production (1999)

Disruption of mitochondrial respiration has been proposed as an action of nitric oxide (NO) responsible for its toxicity, but the effects of NO on the energetics of intact central neurons have not been reported. We examined the effects of NO on mitochondrial function and energy metabolism in cultured hippocampal neurons. The application of NO from NO donors or from dissolved gas produced a rapid, reversible depolarization of mitochondrial membrane potential, as detected by rhodamine-123 fluorescence. NO also produced a progressive concentration-dependent depletion of cellular ATP over 20 min exposures. The energy depletion produced by higher levels of NO (2 microM or more) was profound and irreversible and proceeded to subsequent neuronal death. In contrast to the effects of NO, mitochondrial protonophores produced complete depolarizations of mitochondrial membrane potential but depleted the neuronal ATP stores only partially. Inhibitors of mitochondrial oxidative phosphorylation (rotenone or 3-nitropropionic acid) or of glycolysis (iodoacetate plus pyruvate) also produced only partial ATP depletion, suggesting that either process alone could partially maintain ATP stores. Only by combining the inhibition of glycolytic energy production with the inhibition of mitochondria could the effects of NO in depleting energy and inducing delayed toxicity be duplicated. These results show that NO has rapid inhibitory actions on mitochondrial metabolism in living neurons. However, the severe ATP-depleting effects of high concentrations of NO are not fully explained by the direct effects on mitochondrial activity alone but must involve the inhibition of glycolysis as well. These inhibitory effects on energy production may contribute to the delayed toxicity of NO in vitro and in ischemic stroke.
Manipulation of Avidity to Improve Effectiveness of Adoptively Transferred CD8+ T Cells for Melanoma Immunotherapy in Human MHC Class I-Transgenic Mice (2001)

The adoptive transfer of tumor-reactive CD8(+) T cells into tumor-bearing hosts provides an attractive alternative to vaccination-based active immunotherapy of melanoma. The development of techniques that result in the preferential expansion of tumor-reactive T cells is therefore of great importance. In this study, we report the generation of HLA-A*0201-restricted CD8(+) T cell populations that recognize either tyrosinase(369-376) or gp100(209-217) from tolerant human class I MHC-transgenic mice by using single amino acid-substituted variant peptides. Low peptide concentration or restimulation with the parent peptide was used to enhance the functional avidity, defined by stimulation of IFN-gamma accumulation, and cross-reactivity of the resulting T cell populations. We found a direct correlation between the ability of a T cell population to respond in vitro to low concentrations of the precise peptide expressed on the tumor and its ability to delay the outgrowth of B16 melanoma after adoptive transfer. Surprisingly, we found that some T cells that exhibited high functional avidity and were effective in controlling tumor outgrowth exhibited low structural avidity, as judged by MHC-tetramer staining. Our results establish strategies for the development and selection of CD8(+) T cell populations that persist despite peripheral tolerance, and that can control melanoma outgrowth. Furthermore, they support the use of human MHC class I-transgenic mice as a preclinical model for developing effective immunotherapies that can be rapidly extended into therapeutic settings.
Application of Electroporation Gene Therapy: Past, Current, and Future (2008)

Twenty-five years after the publication of the first report on gene transfer in vitro in cultured cells by the means of electric pulse delivery, reversible cell electroporation for gene transfer and gene therapy (DNA electrotransfer) is at a crossroad in its development. Present knowledge on the effects of cell exposure to appropriate electric field pulses, particularly at the level of the cell membrane, is reported here as an introduction to the large range of applications described in this book. The importance of the models of electric field distribution in tissues and of the correct choice of electrodes and applied voltages is highlighted. The mechanisms involved in DNA electrotransfer, which include cell electropermeabilization and DNA electrophoresis, are also surveyed. The feasibility of electric pulse for gene transfer in humans is discussed taking into account that electric pulse delivery is already regularly used for localized drug delivery in the treatment of cutaneous and subcutaneous solid tumors by electrochemotherapy. Because recent technological developments have made DNA electrotransfer more efficient and safer, this nonviral gene therapy approach is now ready to reach the clinical stage. A good understanding of DNA electrotransfer principles and a respect for safe procedures will be key elements for the successful future transition of DNA electrotransfer to the clinics.
RadA protein is an archaeal RecA protein homolog that catalyzes DNA strand exchange (1998)

With the discovery that the Saccharomyces cerevisiae Rad51 protein is both structurally and functionally similar to the Escherichia coli RecA protein, the RecA paradigm for homologous recombination was extended to the Eucarya. The ubiquitous presence of RecA and Rad51 protein homologs raises the question of whether this archetypal protein exists within the third domain of life, the Archaea. Here we present the isolation of a Rad51/RecA protein homolog from the archaeon Sulfolobus solfataricus, and show that this protein, RadA, possesses the characteristics of a DNA strand exchange protein: The RadA protein is a DNA-dependent ATPase, forms a nucleoprotein filament on DNA, and catalyzes DNA pairing and strand exchange.
Different rhodopsin monoclonal antibodies reveal different binding patterns on developing and adult rat retina. (1987)

We used a battery of 10 monoclonal antibodies directed against different identified peptide sequences within the carboxyl, transmembrane loop, and amino terminal regions of rhodopsin to label retinas from early postnatal and adult rats. Intensity of label, age of initial appearance of staining, and distribution of label varied depending on the antibody. Most antibodies showed detectable labeling at postnatal day 1, and were eventually observed binding to the cell bodies and the inner and outer segments of the photoreceptors. One amino terminal and two carboxyl terminal antibodies, however, showed no detectable labeling until postnatal day 5 and were only transiently detectable in the cell body region. These patterns cannot be explained by accessibility of binding site, binding affinity, fixation artifact, or crossreactivity. The results indicate that physiological and experimental parameters can alter the apparent immunocytochemical localization of conformationally active molecules such as rhodopsin. The results also suggest that rhodopsin can undergo light-dependent conformational changes in several different compartments within rat retinal photoreceptors before the time of eye opening.
Differential Fatty Acid Selection during Biosynthetic S-Acylation of a Transmembrane Protein (HEF) and Other Proteins in Insect Cells (Sf9) and in Mammalian Cells (CV1) (1996)

The transmembrane glycoprotein HEF and its acylation deficient mutant M1 were expressed in Sf9 insect cells infected with recombinant baculovirus and in CV1 mammalian cells using the vaccinia T7 system. In insect cells (Sf9), both wild type HEF and HEF(M1) are synthesized in their precursor form HEF0, which appears as a double band in SDS gels. Digestion with glycopeptidase F and endoglycosidase H reveals that the larger 84-kDa form is modified by the attachment of unprocessed carbohydrates of the high mannose type whereas the smaller 76-kDa form is non-glycosylated. As revealed by in vitro labeling experiments with palmitic acid another modification of HEF is the attachment of a long chain fatty acid to cysteine residue Cys-652 which is located at the internal border of the cytoplasmic membrane. After labeling with [3H]palmitic acid in both systems only HEF(WT) is acylated, whereas HEF(M1) is not. High performance liquid chromatography analysis of the fatty acids bound to HEF(WT) expressed in Sf9 insect cells reveals nearly 80% of palmitic acid. In contrast to this finding, the acylation pattern of HEF expressed in CV1 cells shows nearly the same amounts of stearic and palmitic acid (40%). Since the interconversion of the input [3H]palmitic acid to stearic acid is even lower in CV1 cells than in insect cells, it follows that only HEF expressed in mammalian, but not in insect cells selects for stearic acid during its biosynthetic acylation. We extended our study to acylation of endogenous proteins in Sf9 cells. In finding only palmitate linked to protein we present evidence that, in contrast to mammalian cells, insect cells (Sf9) cannot transfer stearic acid to polypeptide. This finding favors the hypothesis of enzymatic acylation over non-enzymatic mechanisms of acyl transfer to protein.
MDS research criteria for prodromal Parkinson's disease (2015)

This article describes research criteria and probability methodology for the diagnosis of prodromal PD. Prodromal disease refers to the stage wherein early symptoms or signs of PD neurodegeneration are present, but classic clinical diagnosis based on fully evolved motor parkinsonism is not yet possible. Given the lack of clear neuroprotective/disease-modifying therapy for prodromal PD, these criteria were developed for research purposes only. The criteria are based upon the likelihood of prodromal disease being present with probable prodromal PD defined as ≥80% certainty. Certainty estimates rely upon calculation of an individual's risk of having prodromal PD, using a Bayesian naïve classifier. In this methodology, a previous probability of prodromal disease is delineated based upon age. Then, the probability of prodromal PD is calculated by adding diagnostic information, expressed as likelihood ratios. This diagnostic information combines estimates of background risk (from environmental risk factors and genetic findings) and results of diagnostic marker testing. In order to be included, diagnostic markers had to have prospective evidence documenting ability to predict clinical PD. They include motor and nonmotor clinical symptoms, clinical signs, and ancillary diagnostic tests. These criteria represent a first step in the formal delineation of early stages of PD and will require constant updating as more information becomes available.
Preparation of superconducting thin films of bismuth strontium calcium copper oxides by reactive sputtering (1988)

Superconducting thin films of Bi-Sr-Ca-Cu-oxides have been reproducibly prepared by reactive magnetically enhanced triode sputtering using three separate metal targets (Sr, Ca, and Cu-Bi). Oxygen was introduced directly at the substrates during film growth. The films were deposited on ambient temperature substrates [Al2O3, SrTiO3, and yttria-stabilized zirconia (YSZ)] and had thicknesses of 0.5–1.5 μm. After deposition, the films were annealed at 850–900 °C in flowing oxygen. The electrical resistance of the best films on YSZ decreased approximately linearly with temperature until the onset of superconductivity at about 85 K. Zero resistance was achieved by 74 K. Critical current densities in excess of 5×105 A/cm2 at 4.2 K were also obtained. X-ray diffraction demonstrated that the best films were nearly single phase (Bi2Sr2Ca1Cu2O8+x) and textured with the c axis perpendicular to the substrate. The effect of composition and annealing on our results is discussed.
Discrimination between D- and L-tyrosyl transfer ribonucleic acids in peptide chain elongation (1981)

D-Tyr-tRNA can take part in peptide bond formation with N-AcPhe-tRNA on ribosomes programmed with the hexanucleotide UUUUAC. None of the steps leading to peptide bond formation exhibit high stereoselectivity. Ternary complex formation with EF-Tu.GTP favors L-Tyr-tRNA by a factor greater than 25. The complex formed with D-Tyr-tRNA was not protected from hydrolysis, which suggests that the D-amino acid is improperly bound to the protein. The rate of EF-Tu-promoted dipeptide formation was 30-fold faster with L-Tyr-tRNA. The ratio of moles of GTP hydrolyzed to dipeptide formed was 1.4 for L-Tyr-tRNA and 4 for D-Tyr-tRNA. The excess of GTP hydrolyzed to peptide bonds formed is evidence for kinetic proofreading in AA-tRNA selection. The combined effects of the partial discrimination at each stage, from the aminoacylation to the peptide formation, favor L-tyrosine by a factor greater than 10(4) and would virtually exclude D-tyrosine from being incorporated under conditions where L-tyrosine was also present.