gebhart/patrepeval huggingface dataset:
Chronic nonocclusive coronary artery constriction in rats. Beta-adrenoceptor signal transduction and ventricular failure. (1991)

To determine the effects of chronic coronary artery constriction on the relationship between cardiac function and regulation of beta-adrenoceptor signal transduction, the left main coronary artery was narrowed in rats and the animals were killed 5 mo later. An average reduction in coronary luminal diameter of 44% was obtained and this change resulted in an increase in left ventricular end-diastolic pressure and a decrease in positive and negative dP/dt. Significant increases in left and right ventricular weights indicative of global cardiac hypertrophy were observed. Radioligand binding studies of beta-adrenoreceptors, agonist-stimulated adenylate cyclase activity, and ADP ribosylation of 45-kD substrate by cholera toxin were all depressed in the failing left ventricle. In contrast, in the hypertrophic non-failing right ventricle, beta-adrenoreceptor density was preserved and receptor antagonist affinity was increased. In spite of these findings at the receptor level, agonist stimulated cyclic AMP generation was reduced in the right ventricular myocardium. The quantity of the 45-kD substrate was also decreased. In conclusion, longterm nonocclusive coronary artery stenosis of moderate degree has profound detrimental effects on the contractile performance of the heart in association with marked attenuation of adrenergic support mechanisms.
A numerical analysis of a CMOS image sensor with a simple fixed-pattern-noise-reduction technology (2002)

A 1/3-in 640/spl times/480-pixel CMOS image sensor with a simple fixed-pattern noise-reduction technology with a five-transistor pixel circuit and a low input-voltage current-voltage (I-V) converter was previously developed. In this report, we show that the low-input-voltage I-V converter with a current-mirror circuit improves the amplification factor and linearity of the pixel circuit. In a five-transistor pixel circuit, the threshold voltage of the X-Y addressing transistor affects the amplitude and the level of the readout pulse. An analysis of the mechanism of the X-Y addressing transistor shows the basic concept behind the selection of the threshold voltage. An L-shaped readout gate for a pinned photodiode is compared with a straight readout gate, and is proved to be adequate for rapid charge transfer.
Allogeneic reaction induces dendritic cell maturation through proinflammatory cytokine secretion1 (2004)

International audience
Classification of In-vivo Endomicroscopic Images of the Alveolar Respiratory System (2009)

This paper presents an original system for the automatic classification of normal versus abnormal endomicroscopic images of the respiratory alveolar system. Images from the alveoli were acquired in-vivo using a newly developed technique, based on confocal microscopy. The classification process includes a 120feature extraction step followed by an SVM based classification. Results are excellent for non-smoker images and demonstrate the great help of this system for computer-aided diagnosis, using confocal microscopy. 1
Bulletproof business process automation (2003)

The standard unit of work in the business process is the electronic form, which includes complex user interface designs, data gathering and validation, wizard-like behaviors and spreadsheet computations. This paper reports state-of-the-art digital signature methods used to help provide security, non-repudiation and auditability within complex electronic forms applications. Both for financial reasons and for compliance with government regulations such as the Government Paper Elimination Act (GPEA), an ever-increasing number of intricate electronic forms applications are being created. Yet, there are aspects of paper-based systems that can only be modelled if digital signatures are able to omit carefully specified portions of a document so that certain restricted changes can be made after a signature is affixed. These scenarios occur frequently with electronic forms that are multiply signed and possibly involved in a non-trivial workflow process.Due to the importance of securing electronic forms and the complexities that can arise in signing them, the W3C XForms working group has placed integration with XML signatures among the highest priorities of its new standardization charter. However, there are security issues that must be addressed but which are beyond the core cryptographic capabilities of the W3C XML Signature Recommendation. This paper presents our research into and solutions for these issues. The purpose of this paper is to let successful industry experience and academic analysis provide guidance to future secure document standardization efforts (such as XForms) so that, even in the most demanding signature scenarios, the standards are still able to meet the fundamental requirement of digital signatures: What you see is what you sign.
Room Temperature Magnetic Detection of Spin Switching in Nanosized Spin‐Crossover Materials (2012)

Building a better SQUID: A prototype for a SQUID-like magnetometry device for the indirect detection of room-temperature switching in spin-crossover nanoparticles has been developed and used in the study of [Fe(hptrz)3](OTs)2 (hptrz=4-heptyl-1,2,4-triazole, OTs=p-toluenesulfonyl) nanoparticles, as a proof of concept for this novel micromagnetometry approach. The method provides significant benefits over conventional SQUID and nano-SQUID techniques. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. 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.
Quantifying expert diagnosis variability when grading tumor-infiltrating lymphocytes (2017)

Tumor-infiltrating lymphocytes (TILs) have proved to play an important role in predicting prognosis, survival, and response to treatment in patients with a variety of solid tumors. Unfortunately, currently, there are not a standardized methodology to quantify the infiltration grade. The aim of this work is to evaluate variability among the reports of TILs given by a group of pathologists who examined a set of digitized Non-Small Cell Lung Cancer samples (n=60). 28 pathologists answered a different number of histopathological images. The agreement among pathologists was evaluated by computing the Kappa index coefficient and the standard deviation of their estimations. Furthermore, TILs reports were correlated with patient’s prognosis and survival using the Pearson’s correlation coefficient. General results show that the agreement among experts grading TILs in the dataset is low since Kappa values remain below 0.4 and the standard deviation values demonstrate that in none of the images there was a full consensus. Finally, the correlation coefficient for each pathologist also reveals a low association between the pathologists’ predictions and the prognosis/survival data. Results suggest the need of defining standardized, objective, and effective strategies to evaluate TILs, so they could be used as a biomarker in the daily routine.
Measurement and Validation of Benchmark-Quality Thick-Target Tungsten X-Ray Spectra below 150 kVp (2000)

Pulse-height distributions of two constant potential X-ray tubes with fixed anode tungsten targets were measured and unfolded. The measurements employed quantitative alignment of the beam, the use of two different semiconductor detectors (high-purity germanium and cadmium-zinc-telluride), two different ion chamber systems with beam-specific calibration factors, and various filter and tube potential combinations. Monte Carlo response matrices were generated for each detector for unfolding the pulse-height distributions into spectra incident on the detectors. These response matrices were validated for the low error bars assigned to the data. A significant aspect of the validation of spectra, and a detailed characterization of the X-ray tubes, involved measuring filtered and unfiltered beams at multiple tube potentials (30-150 kVp). Full corrections to ion chamber readings were employed to convert normalized fluence spectra into absolute fluence spectra. The characterization of fixed anode pitting and its dominance over exit window plating and/or detector dead layer was determined. An Appendix of tabulated benchmark spectra with assigned error ranges was developed for future reference.
Development of a Branched Radio-Frequency Ion Trap for Electron Based Dissociation and Related Applications (2017)

Collision-induced dissociation (CID) is the most common tool for molecular analysis in mass spectrometry to date. However, there are difficulties associated with many applications because CID does not provide sufficient information to permit details of the molecular structures to be elucidated, including post-translational-modifications in proteomics, as well as isomer differentiation in metabolomics and lipidomics. To face these challenges, we are developing fast electron-based dissociation devices using a novel radio-frequency ion trap (<i>i.e.</i>, a branched ion trap). These devices have the ability to perform electron capture dissociation (ECD) on multiply protonated peptide/proteins; in addition, the electron impact excitation of ions from organics (EIEIO) can be also performed on singly charged molecules using such a device. In this article, we review the development of this technology, in particular on how reaction speed for EIEIO analyses on singly charged ions can be improved. We also overview some unique, recently reported applications in both lipidomics and glycoproteomics.
Charge transfer effects in graphene-CdSe/ZnS quantum dots composites (2012)

Graphene possesses unique physical properties, due to its specific energy bands configuration, substantially different from that of materials traditionally employed in solid-state optoelectronics. Among the variety of remarkable properties, strong field effect, high transparency in the visible-light range and low resistivity of graphene sheets are the most attractive ones for optoelectronic applications. Zero-dimensional colloidal semiconductor nanocrystals, known as quantum dots (QDs), attract immense attention in the field of photonics due to their size-dependent tunable optical properties. By combining these two types of nanomaterials together, we demonstrate the role of graphene as an efficient charge transfer medium from- and to II-VI quantum dots. The optical excitation of II-VI quantum dots dispersed on single layer graphene results in an electron transfer from the nanocrystals to graphene. This is evidenced from photoluminescence imaging and confirmed by the electrical measurements on QDs-decorated single layer graphene field effect transistors (SLG-FET). In the second part of this paper we demonstrate an efficient hole injection from graphene into QDs-layered nanocrystalline structures and the operation of the corresponding graphene-based quantum dot light emitting diodes (QD-LED). We also benchmark graphene vs. indium-tin-oxide (ITO) based QD-LEDs in terms of device electroluminescence intensity performance. Our experimental results show better hole injection efficiency for graphenebased electrode at current densities as high as 200 mA/cm<sup>2</sup> and suggest single layer graphene as a strong candidate to replace ITO in QD-LED technology.
Bridging relational technology and xml (2001)

XML (extensible Markup Language) is fast emerging as the dominant standard for representing and exchanging information over the Internet. These two key applications of XML lead to exciting database opportunities. If data is stored and represented as XML documents, then it should be possible to query the contents of these documents in order to extract, synthesize and analyze their contents. What is the best way to provide this query capability over XML documents? On the other front, if XML is to serve as the medium for information exchange, then it should be possible to convert data stored in existing database systems into XML form for further processing by web-based applications. How do we effectively publish data in existing database systems as XML documents ? 
In this dissertation, we tackle these questions, focusing on the use of relational database technology to answer them. In particular, we make two contributions. First, we present a technique for storing and querying XML documents using a relational database system. This technique enables us to efficiently query XML documents by using a sophisticated, high-performance relational query-processor. Second, we propose and evaluate alternative strategies for efficiently publishing existing relational data as XML documents. These strategies enable us to publish XML documents for electronic-commerce applications, where, for the foreseeable future, most business data will almost certainly continue to be stored in relational database systems.
Small molecules induce mesocrystal formation: nanoparticle aggregation directed by self-assembling calixarenes (2010)

Calixarenes have been shown to induce mesocrystal formation of barium sulfate, despite being relatively low molecular weight additives. Scanning probe microscopy has shown that a possible mechanism is the self-assembling properties of the calixarene resulting in steric stabilization of the nanoparticles, comparable to that typically requiring polymeric additives.
Dynamic Analysis of Current-Voltage Characteristics of Nanoscale Gated-Thyristors (2013)

This letter presents a detailed experimental investigation of the current-voltage characteristics of deca-nanometer gated-thyristors, highlighting that strong differences exist between the static and the dynamic operation of these devices. In particular, results reveal that the forward-breakover voltage determining thyristor turn-on does not depend only on the applied gate voltage, but also on the rise time of the applied gate pulse, decreasing for fast pulse fronts. This is explained in terms of a higher electron injection from the cathode to the anode triggering device turn-on when the gate switching time is shorter than that required for holes to leave the p-base.
Brain cholinergic impairment in liver failure (2008)

The cholinergic system is involved in specific behavioural responses and cognitive processes. Here, we examined potential alterations in the brain levels of key cholinergic enzymes in cirrhotic patients and animal models with liver failure. An increase (~30%) in the activity of the acetylcholine-hydrolyzing enzyme, acetylcholinesterase (AChE) is observed in the brain cortex from patients deceased from hepatic coma, while the activity of the acetylcholine-synthesizing enzyme, choline acetyltransferase, remains unaffected. In agreement with the human data, AChE activity in brain cortical extracts of bile duct ligated (BDL) rats was increased (~20%) compared to controls. A hyperammonemic diet did not result in any further increase of AChE levels in the BDL model, and no change was observed in hyperammonemic diet rats without liver disease. Portacaval shunted rats which display increased levels of cerebral ammonia did not show any brain cholinergic abnormalities, confirming that high ammonia levels do not play a role in brain AChE changes. A selective increase of tetrameric AChE, the major AChE species involved in hydrolysis of acetylcholine in the brain, was detected in both cirrhotic humans and BDL rats. Histological examination of BDL and non-ligated rat brains shows that the subcellular localization of both AChE and choline acetyltransferase, and thus the accessibility to their substrates, appears unaltered by the pathological condition. The BDL-induced increase in AChE activity was not parallelled by an increase in mRNA levels. Increased AChE in BDL cirrhotic rats leads to a pronounced decrease (~50-60%) in the levels of acetylcholine. Finally, we demonstrate that the AChE inhibitor rivastigmine is able to improve memory deficits in BDL rats. One week treatment with rivastigmine (0.6 mg/kg; once a day, orally, for a week) resulted in a 25% of inhibition in the enzymatic activity of AChE with no change in protein composition, as assessed by sucrose density gradient fractionation and western blotting analysis. In conclusion, this study is the first direct evidence of a cholinergic imbalance in the brain as a consequence of liver failure and points to the possible role of the cholinergic system in the pathogenesis of hepatic encephalopathy.
Hen Egg Lysozyme Attenuates Inflammation and Modulates Local Gene Expression in a Porcine Model of Dextran Sodium Sulfate (DSS)-Induced Colitis (2009)

Inflammatory bowel disease (IBD) is a chronic and recurring inflammation of the gastrointestinal tract, associated with a dysregulation of the mucosal immune system. There is an increasing prevalence of IBD; however, current pharmaceutical treatments are only moderately effective and have been associated with potential long-term toxicity. Lysozyme, a well-known antimicrobial protein found in large quantities in hen egg white, is a promising alternative for the treatment of IBD. A porcine model of dextran sodium sulfate (DSS)-induced colitis was used to examine the effect of hen egg lysozyme (HEL) supplementation on intestinal inflammation. Treatment with DSS resulted in weight loss, severe mucosal and submucosal inflammation, colonic crypt distortion, muscle wall thickening, down-regulation of mucin gene expression, and increased gastric permeability, but these symptoms were attenuated following supplementation with HEL and restored to basal levels observed in untreated control animals. Treatment with HEL also significantly reduced the local expression of pro-inflammatory cytokines TNF-alpha, IL-6, IFN-gamma, IL-8, and IL-17 while increasing the expression of the anti-inflammatory mediators IL-4 and TGF-beta, indicating that HEL may function as a potent anti-inflammatory and immunomodulator. Furthermore, the concomitant increases in TGF-beta and Foxp3 levels suggest that HEL may aid in restoring gut homeostasis by activating regulatory T cells, which are important in the regulation of the mucosal immune system. These results suggest that HEL is a promising novel therapeutic for the treatment of IBD.
Analysis of protein-coding genetic variation in 60,706 humans (2020)

Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. We describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of truncating variants with 72% having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human “knockout” variants in protein-coding genes.
The anti‐mitotic agents PTC‐028 and PTC596 display potent activity in pre‐clinical models of multiple myeloma but challenge the role of BMI‐1 as an essential tumour gene (2020)

Future progress in the treatment of multiple myeloma (MM) requires both the characterisation of key drivers of the disease and novel, innovative approaches to tackle these vulnerabilities. The present study focussed on the pre-clinical evaluation of a novel drug class, BMI-1 modulators, in MM. We demonstrate potent activity of PTC-028 and PTC596 in a comprehensive set of in vitro and in vivo models, including models of drug resistance and stromal support. Treatment of MM cells with PTC-028 and PTC596 downregulated BMI-1 protein levels, which was found to correlate with drug activity. Surprisingly, BMI-1 was dispensable for the activity of BMI-1 modulators and MM cell growth. Our data rather point to mitotic arrest accompanied by myeloid cell leukaemia-1 (MCL-1) loss as key anti-MM mechanisms and reveal impaired MYC and AKT signalling activity due to BMI-1 modulator treatment. Moreover, we observed a complete eradication of MM after PTC596 treatment in the 5TGM.1 in vivo model and define epigenetic compounds and B cell leukaemia/lymphoma 2 homology domain 3 (BH3) mimetics as promising combination partners. These results bring into question the postulated role of BMI-1 as an essential MM gene and confirm BMI-1 modulators as potent anti-mitotic agents with encouraging pre-clinical activity that supports their rapid translation into clinical trials.
Enhanced performance of the catalytic conversion of allyl alcohol to 3-hydroxypropionic acid using bimetallic gold catalysts (2011)

One of the strategic building blocks in organic synthesis is 3-hydroxypropionic acid, which is particularly important for the manufacture of high performance polymers. However, to date, despite many attempts using both biological and chemical routes, no large scale effective process for manufacturing 3-hydroxypropionic acid has been developed. One potentially useful starting point is from allyl alcohol, as this can be obtained in principle from the dehydration of glycerol, thereby presenting a bio-renewable green pathway to this important building block. The catalytic transformation of allyl alcohol to 3-hydroxypropionic acid presents interesting challenges in catalyst design, particularly with respect to the control of selectivity among the products that can be expected, as acrylic acid, acrolein and glyceric acid can also be formed. In this paper, we present a novel eco-sustainable catalytic pathway leading to 3-hydroxypropionic acid, which highlights the outstanding potential of gold-based and bimetallic catalysts in the aerobic oxidation of allyl alcohol.
The Pronucleotide Approach. II: Synthesis and Preliminary Stability Studies of Mononucleoside Glycosyl Phosphotriester Derivatives (1997)

Abstract The synthesis and preliminary stability studies of mononucleoside phosphotriester derivatives of 3′-azido-2′,3′-dideoxythymidine (AZT) incorporating a new kind of phosphate protecting group, namely S-glycopyranosidyl-2-thioethyl (SGTE), are reported.