gebhart/patrepeval huggingface dataset:
Adenosine triphosphate infusion increases liver energy status in advanced lung cancer patients: An in vivo 31P magnetic resonance spectroscopy study (2002)

We recently observed inhibition of weight loss in patients with advanced nonsmall-cell lung cancer after intravenous infusion of ATP. Because liver ATP levels were found to be decreased in lung cancer patients with weight loss, the present 31P magnetic resonance spectroscopy (MRS) study was aimed at investigating whether ATP infusion restores liver energy status in these patients. Nine patients with advanced nonsmall-cell lung cancer (stage IIIB/IV) were studied 1 week before (baseline) and at 22 to 24 hours of continuous ATP infusion (37-75 microg/kg/min). Localized hepatic 31P MR spectra (repetition time 15 seconds), obtained in the overnight-fasted state, were analyzed for ATP and P(i) content. Ten healthy subjects (without ATP infusion) served as control. Liver ATP levels in lung cancer patients increased from 8.8 +/- 0.7% (relative to total MR-detectable phosphate; mean +/- SE) at baseline to 12.2 +/- 0.9% during ATP infusion (P <.05), i.e., a level similar to that in healthy subjects (11.9 +/- 0.9%). The increase in ATP level during ATP infusion was most prominent in patients with > or = 5% weight loss (baseline: 7.9 +/- 0.7%, during ATP infusion: 12.8 +/- 1.0%, P < 0.01). In conclusion, ATP infusion restores hepatic energy levels in patients with advanced lung cancer, especially in weight-losing patients. These changes may contribute to the previously reported beneficial effects of ATP infusion on the nutritional status of lung cancer patients.
A Biomarker Assay For The Detection Of Contact System Activation (2013)

Abstract The contact system is composed of circulating plasma proteins that can both initiate coagulation through the intrinsic pathway and promote inflammation through the generation of bradykinin. Activation of the contact system is mediated by the assembly of factor XII (FXII), high molecular weight kininogen (HMWK), and prekallikrein (inactive form of the serine protease plasma kallikrein [pKal]) on a negatively charged surface. Bradykinin is produced from contact system activation by the proteolytic action of active pKal on its substrate HMWK. In vivo, vascular tissue injury or other unknown precipitants may expose negatively charged surfaces capable of supporting contact system activation. In vitro, the contact system is activated following exposure of plasma to substances such as kaolin, dextran sulfate, phospholipids, or surfaces such as glass. We developed a Western blot assay to detect the presence of both intact and cleaved HMWK in human and cynomolgus monkey plasma samples. Using this assay we showed that endogenous HMWK in normal human plasma was converted to cleaved kininogen following the addition of contact system activators, such as kaolin, dextran sulfate, or ellagic acid. HMWK was also shown to be cleaved by the addition of trace amounts of either FXIIa or pKal to normal human plasma. The utility of the Western blot assay was further demonstrated using plasma samples from patients with hereditary angioedema with C1 inhibitor (C1-INH) deficiency (HAE-C1-INH). HAE-C1-INH is a rare, autosomal dominant disease caused by mutations in one of the two alleles of the C1-INH gene (SERPING1). C1-INH is a serine protease inhibitor that blocks the activity of FXIIa and pKal in the contact system. HAE-C1-INH patients suffer from recurrent, localised angioedema attacks due to episodic activation of the contact system arising from unregulated pKal activity, which cleaves HMWK to release bradykinin, a potent vasoactive peptide mediating edema formation. Our results demonstrate that the method could detect significant contact system activation in HAE patient samples collected between attacks (i.e. quiescent disease samples) as compared to normal human plasma. Plasma samples collected during an HAE-C1-INH attack exhibited further elevations in cleaved kininogen. We also measured contact activation in plasma samples from cynomolgus monkeys that were dosed subcutaneously (SC) with DX-2930, a potent and specific monoclonal antibody inhibitor of plasma kallikrein being developed for HAE-C1-INH. DX-2930 blocked the cleavage of HMWK induced by kaolin-mediated contact system activation in a dose-dependent manner (5, 25, or 50 mg/Kg DX-2930, SC). In summary, this study presents a simple method that can be used both to identify disease states associated with contact system activation, and to serve as a pharmacodynamic biomarker for the development of DX-2930 as a treatment for HAE-C1-INH. Disclosures: Faucette: Dyax Corp: Employment. Cicardi:Dyax Corp: Consultancy. Kenniston:Dyax Corp: Employment. Sexton:Dyax Corp: Employment. Adelman:Dyax Corp: Employment.
Correlation between serum levels of IL-15 and IL-17 in patients with idiopathic inflammatory myopathies (2014)

The strong correlation between IL-15 and IL-17 in IIM patients, and especially in DM, suggests that there may be an interplay between the two cytokines in the pathogenesis of myositis. Further studies of larger patient cohorts and of muscle biopsies are needed to confirm these preliminary data.
Differentiation of Heart Failure Related to Dilated Cardiomyopathy and Coronary Artery Disease Using Gadolinium-Enhanced Cardiovascular Magnetic Resonance (2003)

Gadolinium CMR is a powerful technique to distinguish DCM from LV dysfunction related to CAD and yields new insights in DCM. These data suggest that using the coronary angiogram as the arbiter for the presence of LV dysfunction caused by CAD could have lead to an incorrect assignment of DCM cause in 13% of patients, possibly because of coronary recanalization after infarction. The midwall myocardial enhancement in patients with DCM is similar to the fibrosis found at autopsy; it has not previously been visualized in vivo and warrants further investigation. CMR may become a useful alternative to routine coronary angiography in the diagnostic workup of DCM.
The vacB Gene Required for Virulence inShigella flexneri and Escherichia coli Encodes the Exoribonuclease RNase R (1998)

vacB, a gene previously shown to be required for expression of virulence in Shigella and enteroinvasive Escherichia coli, has been found to encode the 3'-5' exoribonuclease, RNase R. Thus, cloning of E. coli vacB led to overexpression of RNase R activity, and partial deletion or interruption of the cloned gene abolished this overexpression. Interruption of the chromosomal copy of vacB eliminated endogenous RNase R activity; however, the absence of RNase R by itself had no effect on cell growth. In contrast, cells lacking both RNase R and polynucleotide phosphorylase were found to be inviable. These data indicate that RNase R participates in an essential cell function in addition to its role in virulence. The identification of the vacB gene product as RNase R should aid in understanding how the virulence phenotype in enterobacteria is expressed and regulated. On the basis of this information we propose that vacB be renamed rnr.
KINETICS STUDY OF THE BIOTRANSFORMATION OF AN OLIGONUCLEOTIDE PRODRUG IN CELLS EXTRACT BY MATRIX-ASSISTED LASER DESORPTION/IONIZATION TIME-OF-FLIGHT MASS SPECTROMETRY (2001)

The fate of a dodecathymidine prodrug in cell extract was monitored by MALDI-TOF MS. This technique allows a facile identification and a relative quantification of metabolites produced. We showed that the relative peak intensities were similar to the relative metabolite proportions that permitted the determination of their half-lives. The oligonucleotide prodrug was fully metabolized to yield the T12 phosphorothioate likely through a carboxyesterase mediated mechanism.
Purification of fibronectin from human plasma by affinity chromatography under non-denaturing conditions (1979)

Fibronectin was purified from human plasma by affinity chromatography under nondenaturing conditions. The method was based on the previously known binding of fibronectin to gelatin. The novel features of our method are the use of arginine in the elution of fibronectin from immobilized gelatin [Vuento & Vaheri (1978) Biochem. J. 175, 333-336] and the use of arginine-agarose as second affinity step. The purified protein was homogeneous as judged by polyacrylamide-gel electrophoresis, analytical ultracentrifugation and two-dimensional immunoelectrophoresis. The yield was 60%. We propose that the method would be useful in preparation of fibronectin for studies on its biological activities, where it is important that the protein is obtained in a native state.
IgE-dependent regulation of human basophil adherence to vascular endothelium. (1989)

Mechanisms favoring the recruitment of circulating human basophils to extravascular sites of allergic inflammation are unknown. The basophil secretagogues anti-IgE, and pollen allergens rye grass I and ragweed Ag E (Lol p I and Amb a I) were tested for their ability to promote basophil adherence to umbilical vein endothelial cells. Co-incubation of endothelial cells and basophils with anti-IgE resulted in time and dose-dependent increases in basophil adhesion. These effects were due to activation of the basophil, required both magnesium and calcium, occurred before or in the absence of histamine release, and were seen at concentrations of stimulus below the usual range of secretagogue activity. In contrast, anti-IgE or Ag stimulation of neutrophils, or basophils from donors non-responsive to anti-IgE or Ag with respect to histamine release, had no effect on cell adherence. mAb 60.3, recognizing the CD18 leukocyte adhesion molecule, inhibited anti-IgE-induced enhancement of basophil-endothelial cell binding. Exposure of basophils to low concentrations of Ag in vivo may selectively initiate basophil infiltration into tissue sites of allergic inflammation by enhancing their adherence to endothelium.
Passivating contacts for homojunction solar cells using a-Si:H/c-Si hetero-interfaces (2014)

Crystalline silicon (c-Si) homojunction solar cells account for over 90% of the current photovoltaic market. However, further progress of this technology is limited by recombinative losses occurring at their metal-semiconductor contacts. The goal of this thesis is to develop passivating contacts to resolve this issue. The novel idea presented in this work is to insert an ultra-thin wide bandgap semiconductor-hydrogenated amorphous silicon (a-Si:H)-film underneath the metal to passivate the doped c-Si surface and suppress the recombination of minority charge carriers. Simultaneously, this layer should provide a contact to the metal allowing majority charge carrier transport. A transparent conductive oxide is additionally inserted between the a-Si:H layer and the metal to ensure efficient carrier collection. This concept is inspired by the silicon heterojunction solar cells, a technology characterized by extremely high open-circuit voltages. The development of these new passivating contacts requires two features: a homojunction, for charge separation, and a silicon heterojunction contact for improved passivation. In this thesis, we explicitly focus on large-area thin-film deposition technology for fabrication of our devices, guaranteeing the scalability of our findings. The main results of this thesis are then threefold. First, we show that, using low-temperature plasma enhanced chemical vapor deposition, a doped homo-epitaxial layer can be deposited to form the homojunction. Second, we develop passivating contacts and optimize them in silicon heterojunction solar cells. An in-depth analysis of the contact formation is provided, including a detailed investigation of the relevant interfaces in our proposed structure. Finally, combining these two technologies, we demonstrate a proof-of-concept for these passivating contacts. Highly doped phosphorus- and boron-doped c-Si surfaces are shown to be efficiently passivated by a-Si:H layers and a lower contact resistivity is obtained for our optimized passivating contacts on such doped surfaces compared to a heterojunction contact on lightly doped surfaces. We show that homojunction solar cells on diffused and ion-implanted wafers featuring such passivating contacts (called homo-hetero cells hereinafter) yield improved open-circuit voltages compared to conventional homojunction solar cells, due to reduction of recombination losses. Additionally, the temperature coefficient of such homo-hetero solar cells is lower. With these advantages, the homo-hetero solar cells outperform homojunction solar cells when operating at a cell temperature above 60 °C. This work contributes to the research and development of high-efficiency silicon solar cells by providing new insights on the properties of contact formation and a novel contact-type.
New analogs of rosaramicin isolated from a Micromonospora strain. II. Structure determination. (1990)

New 16-membered macrolide antibiotics 6108A 1 , B, C and D were isolated from the culture filtrate of a Micromonospora fastidiosus. In this paper, we describe the structure elucidation of these compounds.
A Novel Enzyme That Catalyzes the Esterification of -Acetylsphingosine (1996)

A unique transacylase that catalyzes esterification of a short chain ceramide, N-acetylsphingosine, was found in Madin-Darby canine kidney cell and mouse tissue homogenates. It esterified the hydroxyl group at the carbon-1 position of the ceramide. The enzyme has a pH optimum of 4.2 and a Km of 9.4 microM for N-acetylsphingosine at pH 4.5. The transacylase activity is independent of free fatty acid or acyl-CoA and instead uses the 2-acyl group of phosphatidylethanolamine or phosphatidylcholine. The transacylase activity in the homogenate was present in the 100,000 x g supernatant, and the lipid extracted from the membranous fraction could function as a donor of the acyl group. When liposomes consisting of dioleoylphosphatidylcholine:1-palmitoyl-2-[14C]arachidonoyl-phosphati dylethanolamine:sulfatide (70:0.2:30) were incubated with the supernatant and N-acetylsphingosine, the formation of free arachidonic acid and O-arachidonoyl-N-acetylsphingosine was observed. The ratio of the two products depended on the concentration of ceramide; only the free acid was formed if the truncated ceramide was absent. Both deacylase and transacylase activities were inhibited 50-60% by 20 microM D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol, an inhibitor of several glucosphingolipid synthases. Neither activity was inhibited by nonadecyltetraenyl trifluoromethyl ketone, a potent inhibitor of cytosolic phospholipase A2. N-Acetyldihydrosphingosine and N-octanoylsphingosine were only 55 and 10%, respectively, as effective as N-acetylsphingosine as acyl acceptors. Oleoylsphingosine was only slightly reactive. An esterase that releases the truncated ceramide from its ester linkage appears to be membrane bound. Lecithin was less effective than phosphatidylethanolamine as an acyl donor in the transacylation. Madin-Darby canine kidney cell cultures treated with N-acetyl-[3-3H]sphingosine formed radioactive polar sphingolipids, long chain ceramide, free sphingosine, and O-acyl-N-acetylsphingosine. This suggests that the deacylation and transacylation reactions observed in vitro occur in growing cells as well.
Intrinsic caspase-8 activation mediates sensitization of erlotinib-resistant tumor cells to erlotinib/cell-cycle inhibitors combination treatment (2012)

Inhibitors of the tyrosine kinase activity of epidermal growth factor receptor, as erlotinib, have an established role in treating several cancer types. However, resistance to erlotinib, particularly in breast cancer cell lines, and erlotinib treatment-associated disorders have also been described. Also, methods and combination therapies that could reverse resistance and ameliorate non-desirable effects represent a clinical challenge. Here, we show that the ATP non-competitive CDK2/cyclin A inhibitor NBI1 sensitizes erlotinib-resistant tumor cells to the combination treatment (co-treatment) for apoptosis-mediated cell death. Furthermore, in erlotinib-sensitive cells, the effective dose of erlotinib was lower in the presence of NBI1. The analysis in the breast cancer MDA-MB-468 erlotinib-resistant and in lung cancer A549 cell lines of the molecular mechanism underlying the apoptosis induced by co-treatment highlighted that the accumulation of DNA defects and depletion of cIAP and XIAP activates the ripoptosome that ultimately activates caspases-8 and -10 and apoptosis. This finding could have significant implications for future treatment strategies in clinical settings.
Cytokines in synovial fluid: II. The presence of tumour necrosis factor and interferon. (1988)

Cytokine-specific monoclonal antibodies were used in enzyme-linked immunoadsorbant assays (ELISA) to examine a variety of synovial fluids for the presence of cytokines which might be expected to play some part in the pathology of arthritis. Low, but significant, levels of tumour necrosis factor alpha (TNF-alpha) were present in the majority of synovial fluids obtained from rheumatoid arthritis patients with a sero-positive history. Low levels of interferon (IFN)-alpha and IFN-gamma were also detected, but only IFN-alpha was significantly increased in the sero-positive group. Tumour necrosis factor beta (TNF-beta) was present only in trace amounts. These results suggest that the presence of cytokines, such as TNF-alpha and IFN-alpha in synovial fluid may be associated with tissue changes observed in rheumatoid joint disease and thus contribute to the pathology of the arthritis, but support evidence for the minimal role likely to be played by IFN-gamma in the joint pathology of rheumatoid arthritis.
Prophylaktische Behandlung bei schwerer Hämophilie B mit einem Faktor-IX-Konzentrat (1974)

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study
Metal-responsive elements act as positive modulators of human metallothionein-IIA enhancer activity. (1987)

The human metallothionein IIA (hMT-IIA) gene contains two enhancer elements whose activity is induced by heavy-metal ions such as Cd2+. To determine the nature of the relationship between the metal-responsive elements and the element(s) responsible for the basal activity of the enhancers, the basal-level enhancer element(s), the hMT-IIA enhancers were subjected to mutational analysis. We show that deletion of the metal-responsive elements had no effect on the basal activity of the enhancer but prevented further induction by Cd2+. On the other hand, replacement of the basal-level enhancer element with linker DNA led to inactivation of the enhancer both before and after treatment with Cd2+. Therefore, the metal-responsive elements seems to act as a positive modulator of enhancer function in the presence of heavy-metal ions. In addition to the two enhancers, the hMT-IIA promoter contained one other element, the GC box, required for its basal expression. Unlike deletion of the basal-level enhancer element, replacement of the GC box with linker DNA had no effect on the ability of the promoter to be induced by Cd2+.
Identity resolution (2006)

Identity Resolution is a semantic reconciliation activity as applied to people and organizations. Identity resolution is most frequently quantified in terms of accuracy (false positives and false negatives), however, there are additional metrics by which to evaluate identity resolution algorithms including: methodology, persistence, streaming versus batch, data survivorship, operationalizing historical data, transaction/window size, ingestion speed, end-to-end latency, sequence neutrality, handling of ambiguous conditions, reconcilability, scalability, sustainability, and operational characteristics at scale. As well, a technique for "analytics in the anonymized data space" will be presented that makes it possible to resolve identities in a more privacy-preserving manner.
HMGB1 is a potent trigger of arthritis (2004)

Rheumatoid arthritis is a chronic inflammatory disease characterized by synovial inflammation and structural damage of joints. Although the cause of rheumatoid arthritis (RA) remains unknown, the excessive production of proinflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-1 (IL-1) by intra-articular macrophages occupies a critical pathogenic role in the development and progression of the disease. High mobility group box chromosomal protein 1 (HMGB1) is a recently identified mediator of interest in human and experimental arthritides. HMGB1 can either be actively secreted from macrophages or passively released from necrotic cells of all kinds. Activated macrophages and unprogrammed cell death caused by ischaemia or activated complement are all prominent features of chronic arthritis, contributing to the persistent synovial inflammation. HMGB1 is cytoplasmically and extracellularly overexpressed in inflammatory synovial tissue in human RA as well as experimental collagen-induced arthritis. Elevated levels of HMGB1 are also present in synovial fluid samples from RA patients. Synovial tissue from rats with experimental arthritis exhibits aberrant deposition of HMGB1 preceding the onset of clinical signs of arthritis, and the expression becomes prominent after the onset of clinical disease. The synovial levels of HMGB1 are comparable with those of TNF and IL-1beta at the peak of manifest disease. HMGB1-targeted intervention with either neutralizing antibodies or the antagonistic A box domain of HMGB1 ameliorates collagen-induced arthritis both in mice and rats, and inhibits the local overexpression of IL-1beta in the joints. It is thus conceivable that therapeutic HMGB1 blockade may contribute to future treatment of human chronic arthritis.
The 200‐MeV proton therapy project at the Paul Scherrer Institute: Conceptual design and practical realization (1995)

The new proton therapy facility is being assembled at the Paul Scherrer Institute (PSI). The beam delivered by the PSI sector cyclotron can be split and brought into a new hall where it is degraded from 590 MeV down to an energy in the range of 85-270 MeV. A new beam line following the degrader is used to clean the low-energetic beam in phase space and momentum band. The analyzed beam is then injected into a compact isocentric gantry, where it is applied to the patient using a new dynamic treatment modality, the so-called spot-scanning technique. This technique will permit full three-dimensional conformation of the dose to the target volume to be realized in a routine way without the need for individualized patient hardware like collimators and compensators. By combining the scanning of the focused pencil beam within the beam optics of the gantry and by mounting the patient table eccentrically on the gantry, the diameter of the rotating structure has been reduced to only 4 m. In the article the degrees of freedom available on the gantry to apply the beam to the patient (with two rotations for head treatments) are also discussed. The devices for the positioning of the patient on the gantry (x rays and proton radiography) and outside the treatment room (the patient transporter system and the modified mechanics of the computer tomograph unit) are briefly presented. The status of the facility and first experimental results are introduced for later reference.
Anti‐Lotus Effect for Nanostructuring at the Leidenfrost Temperature (2007)

Nanostructuring at the Leidenfrost temperature is carried out by exposing water-based solution droplets to overheated substrates at temperatures above 200 °C. This method is able to produce nanowires that form different geometries (see figure and inside cover) by inverting the Lotus effect: instead of removing material, moving droplets deposit nanoparticles. Alignment is achieved by employing simple masks. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2089/2007/c1694_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.