gebhart/patrepeval huggingface dataset:
Combined computational and cellular screening identifies synergistic inhibition of SARS-CoV-2 by lenvatinib and remdesivir (2021)

ABSTRACT Rapid repurposing of existing drugs as new therapeutics for COVID-19 has been an important strategy in the management of disease severity during the ongoing SARS-CoV-2 pandemic. Here, we used high-throughput docking to screen 6000 compounds within the DrugBank library for their potential to bind and inhibit the SARS-CoV-2 3CL main protease, a chymotrypsin-like enzyme that is essential for viral replication. For 19 candidate hits, parallel in vitro fluorescence-based protease-inhibition assays and Vero-CCL81 cell-based SARS-CoV-2 replication-inhibition assays were performed. One hit, diclazuril (an investigational anti-protozoal compound), was validated as a SARS-CoV-2 3CL main protease inhibitor in vitro (IC50 value of 29 µM) and modestly inhibited SARS-CoV-2 replication in Vero-CCL81 cells. Another hit, lenvatinib (approved for use in humans as an anti-cancer treatment), could not be validated as a SARS-CoV-2 3CL main protease inhibitor in vitro , but serendipitously exhibited a striking functional synergy with the approved nucleoside analogue remdesivir to inhibit SARS-CoV-2 replication, albeit this was specific to Vero-CCL81 cells. Lenvatinib is a broadly-acting host receptor tyrosine kinase (RTK) inhibitor, but the synergistic effect with remdesivir was not observed with other approved RTK inhibitors (such as pazopanib or sunitinib), suggesting that the mechanism-of-action is independent of host RTKs. Furthermore, time-of-addition studies revealed that lenvatinib/remdesivir synergy probably targets SARS-CoV-2 replication subsequent to host-cell entry. Our work shows that combining computational and cellular screening is a means to identify existing drugs with repurposing potential as antiviral compounds. Future studies could be aimed at understanding and optimizing the lenvatinib/remdesivir synergistic mechanism as a therapeutic option.
Magnetic nanosheets manipulation: Modeling, development and validation (2010)

Polymeric ultra-thin films, also called nanosheets, show peculiar properties in terms of thickness, flexibility and chemical structure. For these reasons, they were proposed as nanoplasters for localized drug release or as a new solution for closing endoluminal surgical wounds. This paper presents the fabrication and characterization of free-standing nanosheets loaded with iron oxide nanoparticles, which can be manipulated in liquid environment by means of magnetic fields. A theoretical model of magnetic manipulation of the nanosheet is proposed and validated by dragging the film with a permanent magnet mounted on an industrial robotic arm. Controlling the magnetic sheet in liquid environment represents a first step towards the application of these nanostructures as free-standing carriers to be released and magnetically controlled in endoluminal surgery or as plasters with nanometric thickness to be delivered in situ on surgical incisions. Furthermore, these magnetic nanofilms can be adapted and used as micro and nanocomponents for the design of a novel generation of magnetic actuated polymeric microrobots.
Real time early detection imaging system of failed wounds and heterotopic ossification using unique Raman signatures (2015)

Our team has established a method to enable imaging of heterotopic ossification and bone growth locations in tissue using Stokes Raman signals with fast acquisition times. This technique relies on the unique Raman signatures of bone to capture parallel, full-field, 1 cm<sup>2</sup> field of view, without utilizing a spectrometer. This system was built in mind as a compact complementary tool for <i>in vivo</i> patient monitoring that can offer a high resolution optical characterization for early detection of failed wounds. Preliminary results of bone detection in flesh are presented here and pave the way for further development of this tool in clinical setting.
Anisotropic Depth Migration of Marine Controlled-Source Electromagnetic Data (2006)

We present a transversely isotropic depth migration scheme for marine controlled-source electromagnetic (MCSEM) data, based on Claerbout&apos;s well-known 45 degree equation from seismic imaging. The proposed scheme is applicable to MCSEM data acquired with a 2-D geometry, and is numerically very efficient. We show examples from field data acquired offshore Norway.
Effect of the Cr-rich oxide surface on fast pumpdown to ultrahigh vacuum (1997)

The outgassing characteristic of an ordinary stainless-steel ultrahigh vacuum (UHV) chamber was determined using an extremely dry nitrogen venting system, and compared with that of an extreme high vacuum (XHV) chamber. A marked sorption resistance effect of the vacuum surface of the XHV chamber was found. The outgassing rate of the XHV chamber was about 100 times lower than that of the ordinary UHV chamber in the unbaked case. It is believed that the recent achievement of fast pumpdown to UHV is the result of not only the reduction of the water content of the venting gas, but also the low gas-sorbability of the vacuum surface.
Respiratory airflow pattern in patients with chronic airway obstruction (1987)

Previous experimental evidence has shown that in healthy humans inspiratory airflow waveform can be optimized according to minimum rate of work criteria when the respiratory energetic requirements become a substantial fraction of the general metabolism (i.e., during exercise hyperpnea and maximum voluntary ventilation). In patients with chronic airway obstruction (CAO) the relative energetic expenditure devoted to respiration is also greatly enhanced at rest. To investigate the performance of a system also controlling airflow wave pattern in this condition we evaluated by Fourier analysis the harmonic content of respiratory flow waves recorded at rest and during exercise hyperpnea (25 and 50 W on cycloergometer) in 15 patients. The results were compared with those we previously obtained in normal subjects and with some theoretical models. It was found that, while normal subjects display at rest an inspiratory flow waveform reasonably close to a sinusoidal model and adopt a more rectangular and economical flow shape during exercise hyperpnea, patients with CAO show a rather rectangular inspiratory flow shape also at rest, without any remarkable change at higher levels of ventilation. So, in general terms, the airflow pattern employed by patients at rest entails a reduction in the rate of dynamic inspiratory work of about 12% over that required by a sinusoidal waveform, and no further advantage is observed during exercise hyperpnea. Some features of the expiratory flow wave were also analysed. As no model of the respiratory system mechanics presently developed can explain the findings obtained in CAO patients purely on the basis of their altered mechanical parameters, it has been suggested that more complex control of respiratory airflow is operating in this class of patient.
Aerobic Exercise Effects on Ocular Dominance Plasticity with a Phase Combination Task in Human Adults (2017)

Several studies have shown that short-term monocular patching can induce ocular dominance plasticity in normal adults, in which the patched eye becomes stronger in binocular viewing. There is a recent study showing that exercise enhances this plasticity effect when assessed with binocular rivalry. We address one question, is this enhancement from exercise a general effect such that it is seen for measures of binocular processing other than that revealed using binocular rivalry? Using a binocular phase combination task in which we directly measure each eye's contribution to the binocularly fused percept, we show no additional effect of exercise after short-term monocular occlusion and argue that the enhancement of ocular dominance plasticity from exercise could not be demonstrated with our approach.
History of ALS (2005)

There are several comprehensive historical accounts of amyotrophic lateral sclerosis (ALS) (1-4). Rather than recapitulate these, I have written a chronological ‘‘Who’s Who’’ in ALS, giving brief biographies of those whose names are linked with the disorder or who have made substantial contributions to the understanding of ALS. As medical science progresses, breakthroughs are made at an even more rapid rate. The importance of recent discoveries, including the identiﬁcation of genetic mutations underlying some familial forms of ALS and the subsequent advent of the transgenic mouse model, is considerable. This chapter is a historical accounting, however, and in order that none should be offended, I have not included contemporary contributions or biographies of living people. Below is a chronological listing of ‘‘Who is Who in ALS,’’ illustrating the stories of those, now deceased, who contributed greatly to the way we view ALS.
PARALLEL MEASUREMENTS OF PROTEIN AND CELL TURNOVER REVEAL HOW TISSUE CONTEXT AND AGING SHAPE PROTEIN LIFETIMES (2022)

Abstract The lifespans of proteins can range from moments to years within mammalian tissues. Protein lifespan is relevant to organismal aging, as long-lived proteins can accrue damage over time. It is unclear how protein lifetime is shaped by tissue context, where both cell division and proteolytic degradation contribute to protein turnover. We have developed turnover and replication analysis by 15N isotope labeling (TRAIL) for parallel quantification of protein and cell lifetimes. We have deployed TRAIL over 32 days in 4 mouse tissues to date to quantify cell proliferation with high precision and no toxicity and determine that protein lifespan varies independently of cell lifespan. Variation in protein lifetime is non-random: multiprotein complexes such as the ribosome have consistent lifetimes across tissues, while mitochondria, peroxisomes, and lipid droplets have variable lifetimes across tissues. To model the effects of aging on tissue homeostasis, we apply TRAIL to a mouse model of Hutchinson-Gilford progeria syndrome and uncover fat-specific alterations in cell lifetime and proteome composition, as well as a broad decrease in protein turnover flux. These data indicate that environmental factors influence protein turnover in vivo and provide a framework to understand proteome aging in tissue context.
Pressure Change Leak Detection Based on Lagrange Interpolation Formula (2017)

The pressure change method of leak testing has the serious disadvantage of being susceptible to ambient temperature change. Two or more successive leak tests are typically performed to eliminate the error caused by such change. We propose a new leak detection scheme in which multiple successive leak tests are performed on the basis of the Lagrange interpolation formula. With this scheme, we can optimally perform multiple successive leak tests for a given temperature variation. After describing the theoretical aspects of the proposed scheme, we will show experimental results of leak detection using a prototype leak detector and model piping. Results indicate that a leak can be detected using the proposed scheme without being affected by the given temperature variation.
Sandwich Materials Selection Charts (2006)

This article presents an approach to facilitate comparison and optimization of sandwich material combinations. Equivalent homogenized sandwich material properties (bending stiffness, density, and cost) are presented graphically in material selection charts to enable an efficient performance per cost evaluation. The effects of core shear deformations and panel production costs can be included in those sandwich material selection charts.
The Proteomics of Sickle Cell Disease: Profiling of Erythrocyte Membrane Proteins by 2D-DIGE and Tandem Mass Spectrometry (2005)

Quantitative changes in the red blood cell membrane proteome in sickle cell disease were analyzed using the two-dimensional fluorescence difference gel electrophoresis 2D-DIGE technique. From over 500 analyzed two-dimensional gel spots, we found 49 protein gel spots whose content in sickle cell membranes were changed by at least 2.5-fold as compared to control cells. In 38 cases we observed an increase and in 11 cases a decrease in content in the sickle cell membranes. The proteins of interest were identified by in-gel tryptic digestion followed by liquid chromatography in line with tandem mass spectrometry. From 38 analyzed gel spots, we identified 44 protein forms representing different modifications of 22 original protein sequences. The majority of the identified proteins fall into small groups of related proteins of the following five categories: actin accessory proteins--four proteins, components of lipid rafts--two proteins, scavengers of oxygen radicals--two proteins, protein repair participants--six proteins, and protein turnover components--three proteins. The number of proteins whose content in sickle RBC membrane is decreased is noticeably smaller, and most are either components of lipid rafts or actin accessory proteins. Elevated content of protein repair participants as well as oxygen radical scavengers may reflect the increased oxidative stress observed in sickle cells.
Potential antiinflammatory agents. Aralkoxyhydrouracils and aralkoxyhydantoins (1970)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPotential antiinflammatory agents. Aralkoxyhydrouracils and aralkoxyhydantoinsLeon Simet, D. B. Reisner, Bernard J. Ludwig, F. Duersch, and Frank Milan BergerCite this: J. Med. Chem. 1970, 13, 6, 1067–1071Publication Date (Print):November 1, 1970Publication History Published online1 May 2002Published inissue 1 November 1970https://pubs.acs.org/doi/10.1021/jm00300a011https://doi.org/10.1021/jm00300a011research-articleACS PublicationsRequest reuse permissionsArticle Views125Altmetric-Citations6LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
A Nonmonotone Line Search Technique and Its Application to Unconstrained Optimization (2004)

A new nonmonotone line search algorithm is proposed and analyzed. In our scheme, we require that an average of the successive function values decreases, while the traditional nonmonotone approach of Grippo, Lampariello, and Lucidi [SIAM J. Numer. Anal., 23 (1986), pp. 707--716] requires that a maximum of recent function values decreases. We prove global convergence for nonconvex, smooth functions, and R-linear convergence for strongly convex functions. For the L-BFGS method and the unconstrained optimization problems in the CUTE library, the new nonmonotone line search algorithm used fewer function and gradient evaluations, on average, than either the monotone or the traditional nonmonotone scheme.
Prediction and Detection of Malicious Insiders' Motivation Based on Sentiment Profile on Webpages and Emails (2018)

Recent high profile data breaches have highlighted the importance of insider threat detection research for cyber security. Anomaly based insider detection approaches are generally associated with high false positives; thus, there has been increased focus on including prediction of user psychology and attack motivations. However, data relating to psychological profile and personality trait of employees are challenging to collect, and do not generally adequately capture attack motivations such as disgruntlement (e.g. towards certain behavior). Therefore, in this paper, we demonstrate how one can build a user psychological profile based on the sentiment analysis of their network browsing and email content. We then evaluate our approach using real-world datasets, and the findings suggest that our approach can proactively and accurately detect malicious insiders with extreme or negative emotional tendencies. This is the first work to build user profile and predict insider threats using sentiment analysis of their browsing and email content.
Interfacial rheology testing of molten polymer systems: Effect of molecular weight and temperature on the interfacial properties (2021)

International audience
Blended Polyphosphazene/Polyacrylonitrile Membranes for Direct Methanol Fuel Cells (2002)

Direct liquid methanol fuel cell tests were performed with membrane electrode assemblies (MEAs) fabricated with polyphosphazene-based proton-exchange membranes. The membranes were prepared from sulfonated poly[bis(3-methylphenoxy)phosphazene] that was blended with polyacrylonitrile and then UV cross-linked using benzophenone as the photoinitiator. MEAs worked best when a high ion-exchange capacity (high conductivity) polyphosphazene membrane contacted the electrodes, in which case the fuel cell power output was nearly the same as that with Nafion 117 (for current densities but the methanol crossover was three times lower than that of Nafion. With a three-membrane composite MEA (a methanol-blocking film sandwiched between two high conductivity membranes), there was a significant decrease in crossover (ten times lower than that of Nafion 117) with a modest decrease in current-voltage behavior. © 2002 The Electrochemical Society. All rights reserved.
Capsular polysaccharides of nongroupable streptococci that cross-react with pneumococcal group 19. (1984)

The cross-reactivity and chemical characterization of the nongroupable streptococcal and pneumococcal group 19 polysaccharides (PS) have been studied. Extensive cross-reactions were observed between capsular PSs of streptococcal strains 14636/74, 4907, 4731 and pneumococcal type 19F and 19A antisera. Streptococcal 14636/74 PS had an identical composition to that of pneumococcal 19F PS. Type 19F and 14636/74 PS were composed of equimolar amounts of rhamnose, glucose, N-acetyl mannosamine, and phosphorus. The capsular PS of strains 4731 and 4907 contained rhamnose, glucose, ribose, N-acetyl mannosamine, and N-acetyl glucosamine in different molar ratios. Extensive immunologic reactivity was observed between the 19F and 14636/74 PS, as determined by light scattering rate nephelometry, passive immune hemolysis, and precipitin reaction. There was an identity reaction by immunodiffusion between type 19F and 14636/74 PS when reacted with rabbit antiserum against either organism. Biochemical studies showed that strain 14636/74 was not a pneumococcus, because it was optochin resistant, was bile insoluble, did not possess the C-carbohydrate antigen common to all pneumococci, and produced neither pneumolysin nor IgA protease. Furthermore, it grew in comparatively simple media in contrast to the complex nutritional requirements of pneumococci. The 13C-NMR spectra of the 19F and 14636/74 PS were identical. These two capsular PS can, therefore, be considered identical.
Computer aided detection via asymmetric cascade of sparse hyperplane classifiers (2006)

This paper describes a novel classification method for computer aided detection (CAD) that identifies structures of interest from medical images. CAD problems are challenging largely due to the following three characteristics. Typical CAD training data sets are large and extremely unbalanced between positive and negative classes. When searching for descriptive features, researchers often deploy a large set of experimental features, which consequently introduces irrelevant and redundant features. Finally, a CAD system has to satisfy stringent real-time requirements.This work is distinguished by three key contributions. The first is a cascade classification approach which is able to tackle all the above difficulties in a unified framework by employing an asymmetric cascade of sparse classifiers each trained to achieve high detection sensitivity and satisfactory false positive rates. The second is the incorporation of feature computational costs in a linear program formulation that allows the feature selection process to take into account different evaluation costs of various features. The third is a boosting algorithm derived from column generation optimization to effectively solve the proposed cascade linear programs.We apply the proposed approach to the problem of detecting lung nodules from helical multi-slice CT images. Our approach demonstrates superior performance in comparison against support vector machines, linear discriminant analysis and cascade AdaBoost. Especially, the resulting detection system is significantly sped up with our approach.
Stoichiometric reductions of alkyl-substituted ketones and aldehydes to borinic esters (2014)

A series of alkyl-substituted ketones are shown to activate hydrogen in the presence of B(C6F5)3, affording the corresponding borinic esters RR'CHOB(C6F5)2. The mechanism is shown to proceed via H2 activation, hydride delivery and protonation of a C6F5 group. The aliphatic aldehyde Et2CHCHO reacts with B(C6F5)3 or BPh3 to give boron enolates Et2C[double bond, length as m-dash]CH(OBAr2) (Ar = C6F5, Ph). These latter species are amenable to FLP-catalyzed reduction to the corresponding borinic esters.
Real-space grids and the Octopus code as tools for the development of new simulation approaches for electronic systems (2015)

Real-space grids are a powerful alternative for the simulation of electronic systems. One of the main advantages of the approach is the flexibility and simplicity of working directly in real space where the different fields are discretized on a grid, combined with competitive numerical performance and great potential for parallelization. These properties constitute a great advantage at the time of implementing and testing new physical models. Based on our experience with the Octopus code, in this article we discuss how the real-space approach has allowed for the recent development of new ideas for the simulation of electronic systems. Among these applications are approaches to calculate response properties, modeling of photoemission, optimal control of quantum systems, simulation of plasmonic systems, and the exact solution of the Schrödinger equation for low-dimensionality systems.
Stability of Pipe Flow with Superposed Solid Body Rotation (1971)

The stability of a flow consisting of solid body rotation superposed on an entrance-type pipe flow profile is investigated experimentally. Increasing the swirl ratios from zero to four reduced the axial Reynolds number at which laminar flow breaks down from 2500 to 900.
Visual Object Class Recognition combining Generative and Discriminative Methods (2007)

Summary form only given. We describe various approaches capable of simultaneous recognition and localization of multiple object classes using a combination of generative and discriminative methods. A first approach uses a novel hierarchical representation allows to represent individual images as well as various objects classes in a single similarity invariant model. The recognition method is based on a codebook representation where appearance clusters built from edge based features are shared among several object classes. A probabilistic model allows for reliable detection of various objects in the same image. A second approach uses a dense representation and a topic distribution model to obtain an intermediate and general representation that is shared across object categories. Combined with discriminative methods these systems show excellent performance on several object categories.