gebhart/patrepeval huggingface dataset:
Beneficial effect of 8-ornithin vasopressin on renal dysfunction in decompensated cirrhosis. (1989)

In nine patients with decompensated alcoholic cirrhosis of the liver and impaired renal function the effect of 8-ornithin vasopressin (ornipressin) on renal function and haemodynamic parameters was studied. Ornipressin was infused at a dose of 6 IU/h over a period of four hours. During ornipressin infusion an improvement of renal function was achieved as indicated by an increase of creatinine clearance (76 (15)%; p less than 0.01), urine volume (108 (29)%; p less than 0.05) and sodium excretion (168 (30)%; p less than 0.05). The hyperdynamic circulation of hepatic failure, as characterised by increased cardiac index and heart rate as well as decreased systemic vascular resistance was reversed to a nearly normal circulatory state during ornipressin infusion. The raised noradrenaline plasma concentration (1.74 (0.31) ng/ml) and plasma renin activity (13.5 (3.9) ng/ml/h) were lowered during ornipressin infusion to 0.87 (0.21) ng/ml and 5.9 (2.1) ng/ml/h, respectively (p less than 0.01). The efficacy of a vasoconstrictor agent in reverting a hyperdynamic state and improving renal function provides evidence for the substantial role of accumulation of vasodilator substances and subsequent activation of sympathetic nervous system and renin-angiotensin-axis in the pathogenesis of renal dysfunction in hepatic failure. Values are expressed as mean (SE).
Toward an Electronic Copyright Management System (1993)

Work is going forward at CNRI, in conjunction with ARPA and the Library of Congress, on the design and implementation of an Electronic Copyright Management System (EMCS) to demonstrate the licensing of rights and permissions, payment of any royalties, and the electronic deposit, registration, and recordation of copyright works and related documents in a computer network environment. A variety of economic, social, and legal issues need to be addressed by both rightsholders and users in the course of this project. Cooperation among the copyright, computer, and communications industries concerned, taking into account the balance between protection for copyright works and the needs of the public for access to information, is essential if such a capability is to become a valuable marketplace tool. © 1993 John Wiley & Sons, Inc.
Binding of wild type and chimeric arrestins to the m2 muscarinic cholinergic receptor (1993)

Arrestins play an important role in regulating the activity of the G protein-coupled receptors rhodopsin and the beta 2-adrenergic receptor. Recently, we described the expression and functional characterization of visual arrestin using an in vitro translation system. Here we report the expression of beta-arrestin and development of a direct binding assay to study the interaction of arrestins with a muscarinic cholinergic receptor. In vitro translated beta-arrestin was found to specifically bind to purified reconstituted human m2 muscarinic cholinergic receptor (hm2 mAChR) in an agonist- and phosphorylation-dependent manner. Visual arrestin also bound to the hm2 mAChR, albeit to a lesser extent and with lower affinity. In an attempt to dissect the major domains responsible for determining the receptor binding specificity of arrestin and beta-arrestin, we generated several chimeric arrestins. One contained the first 340 residues of beta-arrestin followed by residues 346-404 of arrestin (BRV4), another consisted of the first 207 residues of beta-arrestin and residues 214-404 of visual arrestin (BV3), and a third had residues 1-43 of beta-arrestin replaced by residues 1-47 of arrestin (VIN1). All of these arrestins were able to specifically bind to the activated and phosphorylated form of both the hm2 mAChR and rhodopsin, with a clear preference for the muscarinic receptor. The Kd values for beta-arrestin, BRV4, BV3, VIN1, and visual arrestin binding to the hm2 mAChR were 0.48 +/- 0.06, 0.51 +/- 0.19, 1.38 +/- 0.26, 1.13 +/- 0.26, and 7.2 +/- 1.2 nM, respectively. These data demonstrate that: 1) beta-arrestin binds to the hm2 mAChR in an activation- and phosphorylation-dependent fashion, 2) visual arrestin has 15-fold lower affinity for the hm2 mAChR as compared to beta-arrestin, and 3) the N-terminal half of beta-arrestin plays a key role in determining receptor binding specificity. The use of in vitro translated arrestins to directly assess receptor binding may serve as a viable approach for elucidating the specificity and molecular mechanisms involved in receptor-arrestin interaction.
Human OX40 tunes the function of regulatory T cells in tumor and nontumor areas of hepatitis C virus–infected liver tissue (2014)

Our data demonstrate that Tregs can finely adapt, or even subvert, their classical inhibitory machinery in distinct microenvironments within the same organ.
Precision proteomics: The case for high resolution and high mass accuracy (2008)

Proteomics has progressed radically in the last 5 years and is now on par with most genomic technologies in throughput and comprehensiveness. Analyzing peptide mixtures by liquid chromatography coupled to high-resolution mass spectrometry (LC-MS) has emerged as the main technology for in-depth proteome analysis whereas two-dimensional gel electrophoresis, low-resolution MALDI, and protein arrays are playing niche roles. MS-based proteomics is rapidly becoming quantitative through both label-free and stable isotope labeling technologies. The latest generation of mass spectrometers combines extremely high resolving power, mass accuracy, and very high sequencing speed in routine proteomic applications. Peptide fragmentation is mostly performed in low-resolution but very sensitive and fast linear ion traps. However, alternative fragmentation methods and high-resolution fragment analysis are becoming much more practical. Recent advances in computational proteomics are removing the data analysis bottleneck. Thus, in a few specialized laboratories, "precision proteomics" can now identify and quantify almost all fragmented peptide peaks. Huge challenges and opportunities remain in technology development for proteomics; thus, this is not "the beginning of the end" but surely "the end of the beginning."
A Radiation Dosimetry Method Using Pulsed Optically Stimulated Luminescence (1999)

Journal Article A Radiation Dosimetry Method Using Pulsed Optically Stimulated Luminescence Get access M.S. Akselrod, M.S. Akselrod Search for other works by this author on: Oxford Academic PubMed Google Scholar S.W.S. McKeever S.W.S. McKeever Search for other works by this author on: Oxford Academic PubMed Google Scholar Radiation Protection Dosimetry, Volume 81, Issue 3, 1 February 1999, Pages 167–175, https://doi.org/10.1093/oxfordjournals.rpd.a032583 Published: 01 February 1999
Protein Aggregation in the Aging Retina (2010)

The age-related altered expression of neuron-related proteins as seen in other regions of the central nervous system is expected in the aging retina. Using immunohistochemical techniques, we characterized the distribution and aggregation of tau, βA4-amyloid, α-synuclein, and ubiquitin in human retina obtained from 19 enucleated eyes of patients aged 49 to 87 years and correlated the findings with the ages. Using a phosphorylation-independent antibody, tau aggregates were observed within the cytoplasm of several photoreceptor cells, and there was a positive correlation between age and the number of tau-positive ganglionic cells. Tau deposits were immunonegative with a phosphorylation-dependent antibody. We did not observe βA4-amyloid in subretinal pigment epithelium deposits or in neuroepithelial layers. α-Synuclein and ubiquitin inclusions were found in the inner nuclear layer, and there was colocalization of these proteins. The proportion of patients displaying such α-synuclein and/or ubiquitin intracytoplasmic inclusions was significantly higher with aging. The presence of ubiquitin deposits within drusen was remarkable, but diffuse ubiquitin aggregates between the retinal pigment epithelium and Bruch membrane were also noticed. These results indicate that protein aggregation in the retina increases with aging and that tau, α-synuclein, and ubiquitin should be the subjects of future investigations.
Cell-permeable probe for identification and imaging of sialidases (2013)

Alkyne-hinged 3-fluorosialyl fluoride (DFSA) containing an alkyne group was shown to be a mechanism-based target-specific irreversible inhibitor of sialidases. The ester-protected analog DFSA (PDFSA) is a membrane-permeable precursor of DFSA designed to be used in living cells, and it was shown to form covalent adducts with virus, bacteria, and human sialidases. The fluorosialyl-enzyme adduct can be ligated with an azide-annexed biotin via click reaction and detected by the streptavidin-specific reporting signals. Liquid chromatography-mass spectrometry/mass spectrometry analysis on the tryptic peptide fragments indicates that the 3-fluorosialyl moiety modifies tyrosine residues of the sialidases. DFSA was used to demonstrate influenza infection and the diagnosis of the viral susceptibility to the anti-influenza drug oseltamivir acid, whereas PDFSA was used for in situ imaging of the changes of sialidase activity in live cells.
Acetate kinase from Clostridium acetobutylicum: a highly specific enzyme that is actively transcribed during acidogenesis and solventogenesis (1997)

Acetate kinase (ATP:phosphotransferase, EC 2.7.2.1) has been purified 294-fold from acid-producing cells of Clostridium acetobutylicum DSM 1731 to a specific activity of 1087 U mg-1 (ADP-forming direction). The dimeric enzyme consisted of subunits with a molecular mass of 43 kDa. The molecular mass of the native acetate kinase was in the range 87-94 kDa as judged by gel filtration and native gel electrophoresis. The enzyme showed high specificity for the substrates acetate and ATP, and maximal activity was obtained with Mn2+ as divalent cation. The presence of mercury compounds such as HgCl2 and p-hydroxymercuribenzoate resulted in an essential loss of activity. The apparent K(m) values of acetate, Mg-ATP, acetyl phosphate, and Mg-ADP were 73, 0.37, 0.58 and 0.71 mM. An activity-staining procedure for detection of acetate kinase in crude cell extracts after separation on native polyacrylamide gels was developed. A DNA fragment encoding 246 bp of the acetate kinase gene of C. acetobutylicum DSM 792 was cloned by a PCR-based approach. Northern blot analysis revealed transcription of the gene under acid- and solvent-producing conditions with no significant differences at the level of transcription.
Robots in Laparoscopic Surgery (2001)

This early experience suggests that robotic surgery is a safe and effective alternative to conventional laparoscopic surgery. We believe that robotic surgery, with its ability to restore the hand-eye coordination and three-dimensional view lost in laparoscopic surgery, will allow us to perform complex procedures with greater precision and confidence and better results.
A Hyperfusogenic Gibbon Ape Leukemia Envelope Glycoprotein: Targeting of a Cytotoxic Gene by Ligand Display (2000)

An important goal in cancer gene therapy is the development of novel targeted cytotoxic genes. The observation that transfection of a GaLV envelope glycoprotein lacking an R peptide into human cells results in considerable cell-cell fusion and subsequent cell death prompted us to explore the potential for using this fusogenic membrane glycoprotein (FMG) as a targeted cytotoxic gene. As proof of principle, we therefore displayed epidermal growth factor (EGF) on the N terminus of GaLV envelope glycoproteins both with and without an R peptide (GaLV R+ and GaLV R-). Transfection of the GaLVR+ envelope expression plasmids did not cause cell-cell fusion. The GaLV R+ envelopes were incorporated into retroviral vectors whose infectivity was investigated on EGF receptor-positive and -negative cells. The vector incorporating an N-terminally unmodified envelope was able to infect all human cell lines tested. Infectivity of the vector incorporating an envelope on which EGF was displayed was restricted on EGF receptor-positive cells (but not on EGF receptor-negative cells) and could be restored by protease cleavage of the displayed domain or competition with exogenous ligand. The cell-cell fusion capacity of the GaLV R- envelope glycoproteins (N-terminally unmodified and with N-terminal display of both EGF and insulin-like growth factor I [IGF-I]) was investigated by plasmid DNA transfection. While the N-terminally unmodified GaLV R- fused all human cell types tested, fusogenicity of GaLV R- on which EGF or IGF-I was displayed was considerably restricted on receptor-positive cells. "Reciprocal" competition experiments showed that fusogenicity could be restored by competition only with the relevant exogenous ligand. Thus the specificity of cell-cell fusion by a hyperfusogenic GaLV envelope glycoprotein can be regulated by N-terminal display of growth factor ligands. There is therefore significant potential for further development of the targeting of the cell-killing capability of this fusogenic viral glycoprotein by using strategies similar to those we have developed for the targeting of retroviral vectors.
Haemodialysis with on-line monitoring equipment: tools or toys? (2005)

On-line monitoring devices and bio-feedback systems have evolved from toys for research use to tools for routine clinical application, particularly in patients with clinical complications. Conductivity monitoring appears the most versatile tool, as it permits quantification of delivered dialysis dose, achievement of sodium balance and surveillance of vascular access function, potentially at each dialysis session and without extra cost.
Synthesis and Biological Evaluation of 4-Anilinoquinolines as Potent Inhibitors of Epidermal Growth Factor Receptor (2010)

The mutant receptor tyrosine kinase EGFR is a validated and therapeutically amenable target for genotypically selected lung cancer patients. Here we present the synthesis and biological evaluation of a series of 6- and 7-substituted 4-anilinoquinolines as potent type I inhibitors of clinically relevant mutant variants of EGFR. Quinolines 3a and 3e were found to be highly active kinase inhibitors in biochemical assays and were further investigated for their biological effect on EGFR-dependent Ba/F3 cells and non-small cell lung cancer (NSCLC) cell lines.
The Dual Role Played by p21 May Influence the Apoptotic or Anti-Apoptotic Fate in Cancer (2012)

p21 is a cyclin-dependent kinase inhibitor that is activated in response to different stress stimuli and could act as cell cycle suppressor. p21 can bind and inhibit cyclin-dependent kinase/cyclin complexes to mediate growth arrest in G1 and G2 phases. This condition enables DNA repair and suggests that p21 could have a role of tumour suppressor. p21 is one of the transcriptional targets of p53, a protein up-regulated after cellular stress stimuli. Besides the classical p53-dependent activation, p21 transcription can be achieved by other regulators as Sp1, STAT and AP2 in a p53-independent manner. Depending on cell type and cellular conditions p21 can have anti-apoptotic or pro-apoptotic functions being involved either in tumourigenesis or in tumour suppression. The function exerted is based on subcellular localization. In the nucleus p21 inhibits proliferation by blocking the cyclin dependent kinases while in the cytoplasm it acts inhibiting pro-apoptotic protein determining cell death inhibition. The different subcellular localization is related to different prognostic role of p21 in cancer and the cellular context in which it is expressed determines if it can be considered as a specific therapeutic target or as a marker of poor prognosis. This review focuses on the recent understanding of the functions of p21 with particular attention to the dual role detected in cancer where p21 can act as tumour suppressor promoting apoptosis or as oncogene preventing it.
Probing the Origin of Enhanced Stability of “AlPO4” Nanoparticle Coated LiCoO2 during Cycling to High Voltages: Combined XRD and XPS Studies (2009)

“AlPO4”-coated LiCoO2 was shown to exhibit markedly improved capacity retention and reduced impedance growth relative to bare “LiCoO2” upon cycling to 4.7 V. Scanning electron microscopy imaging showed that the surfaces of the cycled bare “LiCoO2” particles remained very smooth whereas there were many newly formed patches distributed on the surfaces of the cycled coated particles. X-ray powder diffraction analyses revealed that select peak broadening was observed for cycled bare electrodes suggesting that structural damage to LixCoO2 was introduced upon cycling. In contrast, no apparent structural changes to LixCoO2 were found for cycled coated electrodes. Pristine and cycled bare and “AlPO4”-coated LiCoO2 electrodes were studied by X-ray photoelectron spectroscopy. No significant change was detected in the surface chemistry of Co for cycled bare electrodes, but surface LiF and LixPFyOz components were found to considerably increase during cycling, which led to partial surface coverage of LixCoO2. A very small amount of Co-containing oxyfluoride species was detected on the cycled bare electrodes while considerable amounts of Co-containing and Al-containing fluorides and/or oxyfluorides and species such as PFx(OH)y were found on the cycled coated electrodes, which completely covered the surfaces of the LixCoO2 particles. The mechanism responsible for the enhanced cycling stability and reduced impedance of coated relative to bare electrodes is discussed in detail.
X-linked retinitis pigmentosa. (1975)

Of 107 consecutive patients with genetically-determined retinitis pigmentosa, 23 were provisionally diagnosed as having inherited the disease in an X-linked fashion. 42 affected males and 61 females were examined, and from the data obtained the following conclusions were drawn: (1) X-linked retinitis pigmentosa exists and is distinct from choroideremia. (2) In contrast to the results of previous surveys, X-linked retinitis pigmentosa is a common form of this disease and over 20 per cent. of retinitis pigmentosa is probably transmitted in an X-linked manner. (3) (a) In contradistinction to the findings of previous investigators, most if not all adult heterozygous females have detectable degenerative changes in the ocular fundus. (b) The ocular changes in heterozygous females are most easily detected by fundus examination, visual field testing, dark adaptation measurements, and estimation of retinal rhodopsin concentration. The single most frequent abnormality is peripheral retinal pigment epithelial atrophy, which is found in all adult heterozygous females. (c) The pattern of retinal dysfunction in heterozygous females, and in particular preservation of the ocular electrical responses, suggests that the disease in women is qualitatively different from that in men and in other genetic forms of retinitis pigmentosa. There is some evidience that the disease in heterozygous women is patchy. (d) Degeneration in heterozygous females is usually symmetrical, but great variation was found in the severity of degeneration amongst heterozygotes of similar ages. No non-genetic influences were found to account for this. No evidence came to light by which the importance of X-chromosome inactivation could be assessed in determining the phenotype of heterozygous women. (4) No evidience is available to determine the number of X-linked genes transmitting the disease.
Development of FUB 181, a Selective Histamine H3-Receptor Antagonist of High Oralin Vivo Potency with 4-(?gv-(Arylalkyloxy)alkyl)-1H-imidazole Structure (1998)

A series of 4-(omega-(arylalkyloxy)alkyl)-1H-imidazoles and related sulphur-containing compounds have been prepared and evaluated for their histamine H3-autoreceptor antagonist in vitro potency in an assay on synaptosomes of rat cerebral cortex. In addition, the in vivo potency has been determined from the changes in N tau-methylhistamine levels in brain after p.o. administration to mice. Compounds with different alkyl chains and various aryl moities have been synthesized and tested to explore structure-activity relationships. Within this series of novel antagonists, (1H-imid-azol-4-yl)methyl and 2-(1H-imidazol-4-yl)ethyl ether derivatives showed low to moderate H3-receptor antagonist potency, whereas the corresponding allyl and propyl derivatives were compounds with high antagonist in vitro potency. Corresponding thioether or sulphoxide derivatives also showed antagonists activity. Additionally, some ether derivatives possessed high in vivo potency as well. The most active ether derivatives under in vivo conditions were 4-(3-(3-(4-fluorophenyl)propyloxy)propyl)-1H-imidazole (11b) and the corresponding chloro compound 11c (FUB 181) with ED50 values of 0.76 and 0.80 mg/kg, respectively. On the other hand, all compounds tested showed weak activity at histamine H1 or H2 receptors. Furthermore, the most promising ether FUB 181 exhibited low activity at adrenergic alpha 1, beta 1/2, serotonergic 5-HT2A, 5-HT3, and muscarinic M3 receptors. Time-course investigations of FUB 181 in mice showed a rapid mode of action with the highest value 3 h after p.o. application. Thus, FUB 181 appears to block histamine H3 receptors potently and selectively.
The Analytical Approach to Polydimethylsiloxane Microfluidic Technology and Its Biological Applications (2006)

This review article discusses PDMS (polydimethylsiloxane) microfluidic devices and their biological applications. First, the already developed devices are classified from the viewpoints of underlying technology within a common logical framework comprising single-layer, multilayer, and integrated devices, as well as surface chemistry modifications of PDMS. Combinatorial techniques are applied to re-derive existing devices within this framework. Next, the relevant scales of both microfluidics and biology are compared, obtaining the promise and limitations of PDMS microfluidics. Finally, the body of work is reclassified in terms of addressed biological applications and compared to the standard methods in cellular and molecular biology, to offer insights for future devices and applications.
Parameter optimization of awavelet-based electrocardiogram delineator with an evolutionary algorithm (2005)

A recurrent problem encountered in many algorithms proposed to detect and segment ECG waves is the adjustment of the numerous parameters used. This work presents a method to optimize these parameters with an evolutionary algorithm (EA). The signal processing chain contains a filter to remove baseline wandering, a QRS detector (Pan & Tompkins) and a wave segmentation step based on the wavelet-transform (WT). The EA adjusts the parameters of the segmentation step in order to minimize the result of a cost function which measures how close the detector is from characteristic points annotated by a cardiologist. Results obtained with the QTDB are compared with other approaches of wave segmentation for which thresholds have been experimentally defined. EAs have shown to be an effective method to solve this complex problem of multiobjective optimization
Convection warmers — not just hot air (1997)

We sought to determine whether the forced air convection warmers (nine Bair Huggers, Augustine Medical, and one Warm Touch, Mallinkrodt Medical) used in our operating theatres could be a source of microbial pathogens. Agar plates were placed directly in the air stream of the warmers. Four of these grew potentially pathogenic organisms. When the warmers were set to blow through perforated blankets, no growth occurred. Three of the warmers were swabbed and sites of colonisation were found in their hoses. After fixing a microbial filter to the end of the hose, organisms were no longer detectable. We conclude that these warming devices are a potential source of nosocomial infection. They should only be used in conjunction with perforated blankets, should have their microbial filters changed regularly and their hoses sterilised. The inclusion of a microbial filter into the nozzle of the hose could be incorporated into the design of the warmer.