gebhart/patrepeval huggingface dataset:
NRF2 deficiency replicates transcriptomic changes in Alzheimer's patients and worsens APP and TAU pathology (2017)

Failure to translate successful neuroprotective preclinical data to a clinical setting in Alzheimer's disease (AD) indicates that amyloidopathy and tauopathy alone provide an incomplete view of disease. We have tested here the relevance of additional homeostatic deviations that result from loss of activity of transcription factor NRF2, a crucial regulator of multiple stress responses whose activity declines with ageing. A transcriptomic analysis demonstrated that NRF2-KO mouse brains reproduce 7 and 10 of the most dysregulated pathways of human ageing and AD brains, respectively. Then, we generated a mouse that combines amyloidopathy and tauopathy with either wild type (AT-NRF2-WT) or NRF2-deficiency (AT-NRF2-KO). AT-NRF2-KO brains presented increased markers of oxidative stress and neuroinflammation as well as higher levels of insoluble phosphorylated-TAU and Aβ*56 compared to AT-NRF2-WT mice. Young adult AT-NRF2-KO mice exhibited deficits in spatial learning and memory and reduced long term potentiation in the perforant pathway. This study demonstrates the relevance of normal homeostatic responses that decline with ageing, such as NRF2 activity, in the protection against proteotoxic, inflammatory and oxidative stress and provide a new strategy to fight AD.
Sphingomyelinase decreases transepithelial anion secretion in airway epithelial cells in part by inhibiting CFTR‐mediated apical conductance (2021)

The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel whose dysfunction causes cystic fibrosis (CF). The loss of CFTR function in pulmonary epithelial cells causes surface dehydration, mucus build-up, inflammation, and bacterial infections that lead to lung failure. Little has been done to evaluate the effects of lipid perturbation on CFTR activity, despite CFTR residing in the plasma membrane. This work focuses on the acute effects of sphingomyelinase (SMase), a bacterial virulence factor secreted by CF relevant airway bacteria which degrades sphingomyelin into ceramide and phosphocholine, on the electrical circuitry of pulmonary epithelial monolayers. We report that basolateral SMase decreases CFTR-mediated transepithelial anion secretion in both primary bronchial and tracheal epithelial cells from explant tissue, with current CFTR modulators unable to rescue this effect. Focusing on primary cells, we took a holistic ion homeostasis approach to determine a cause for reduced anion secretion following SMase treatment. Using impedance analysis, we determined that basolateral SMase inhibits apical and basolateral conductance in non-CF primary cells without affecting paracellular permeability. In CF primary airway cells, correction with clinically relevant CFTR modulators did not prevent SMase-mediated inhibition of CFTR currents. Furthermore, SMase was found to inhibit only apical conductance in these cells. Future work should determine the mechanism for SMase-mediated inhibition of CFTR currents, and further explore the clinical relevance of SMase and sphingolipid imbalances.
Precise Probing of Residue Roles by Post-Translational β,γ-C,N Aza-Michael Mutagenesis in Enzyme Active Sites (2017)

Biomimicry valuably allows the understanding of the essential chemical components required to recapitulate biological function, yet direct strategies for evaluating the roles of amino acids in proteins can be limited by access to suitable, subtly-altered unnatural variants. Here we describe a strategy for dissecting the role of histidine residues in enzyme active sites using unprecedented, chemical, post-translational side-chain-β,γ C-N bond formation. Installation of dehydroalanine (as a "tag") allowed the testing of nitrogen conjugate nucleophiles in "aza-Michael"-1,4-additions (to "modify"). This allowed the creation of a regioisomer of His (iso-His, His<sub>iso</sub>) linked instead through its pros-Nπ atom rather than naturally linked via C4, as well as an aza-altered variant aza-His<sub>iso</sub>. The site-selective generation of these unnatural amino acids was successfully applied to probe the contributing roles (e.g., size, H-bonding) of His residues toward activity in the model enzymes subtilisin protease from <i>Bacillus lentus</i> and <i>Mycobacterium tuberculosis</i> pantothenate synthetase.
Crossed patch arrangements of linear triangular elements for upper bound finite-element analysis of plane strain deformation problems (2010)

In standard linear finite-element formulations, volumetric locking because of the incompressibility constraint that may occur in computational plasticity is often encountered. This study uses crossed patch arrangements of triangles to form quadrilateral elements in order to overcome the locking in the upper bound finite-element analysis of plane strain deformation problems. The velocity field is described in terms of linear triangular elements, while the incompressibility constraint is imposed by quadrilateral elements. Rigid, perfectly plastic materials, and strain hardening materials that form the von Mises model have been considered. The velocity formulation is presented and has been implemented in a finite-element code. Several examples, some benchmarks problems, are presented to illustrate the applicability of the approach for predicting the load, strain, and velocity field during the plastic deformation. Numerical results show that the crossed patch arrangements of linear triangular elements are free of volumetric locking and achieve well-defined limit loads. This study shows that the presented method can be used to simulate large plastic deformation under plane strain conditions.
Perspectives on Intravenous Oxycodone for Control of Postoperative Pain (2015)

Intravenous (IV) analgesia has particular advantages in the immediate postoperative period. For example, IV administration results in a faster onset of pain relief and results in more predictable pharmacokinetics than does administration by other routes. It also allows for convenient dosing before or during surgery, permitting the initiation of effective analgesia in the early phase of the postoperative period. In addition, when patients are able to tolerate oral intake, they can be switched from IV to oral dosing based on maintaining the predictable analgesia established by the IV route. IV morphine is widely used for the control of postoperative pain, but there is a trend toward the use of oxycodone. Oxycodone (which may be mediated partly through kappa- as well as mu-opioid receptors) offers several potential advantages. Published studies comparing IV oxycodone to other IV opioids for postsurgical pain report that oxycodone is a safe and effective analgesic. Some studies show that IV oxycodone may be associated with greater pain control, fewer or less severe adverse events, and faster onset of action, although the results are not consistent across all studies. Oxycodone has been reported to be safe in the geriatric and other special populations when adequate clinical adjustments are made. Thus, the clinical reports and oxycodone's pharmacologic profile make intravenous oxycodone a potentially important "new" old drug for postoperative pain control.
Analysis of Macrocyclic Polystyrenes. 1. Liquid Chromatographic Investigations (1996)

Macrocyclic polystyrenes prepared by a single-step, pseudo-unimolecular cyclization of a linear α-(diethoxyethyl)-ω-styrenylpolystyrene can effectively be analyzed by liquid chromatography at the critical point of adsorption. Using silica gel as the stationary phase and THF−hexane as the eluent, the macrocyclic oligomers are separated from their linear precursors and other nonfunctional linear oligomers. The quantitative determination of the cyclization yield can be carried out via appropriate detector calibration for the linears and cyclics. Additional information on the chemical structure of the linears and cyclics is obtained by matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. In conclusion, a possible cyclization mechanism is given including an interpretation of the MALDI behavior of the samples.
A translational effort to identify prognostic and predictive biomarkers in pancreatic cancer among RBM3-regulated genes. (2018)

305 Background: Pancreatic cancer has a dismal prognosis and clinical protocols are still lacking predictive biomarkers. RNA-binding motif protein 3 (RBM3) has emerged as a promising biomarker in several solid cancers, including pancreatic cancer. High RBM3 expression in human tumors has been associated with good response to chemotherapy, as well as to confer increased chemosensitivity in vitro. The aim of this study was to identify RBM3-regulated genes in pancreatic cells in vitro, and further interrogate their potential utility as prognostic and predictive biomarkers in a translational setting. Methods: Next generation RNA-sequencing was applied to compare gene expression between MIAPaCa-2 cells with siRNA-downregulated RBM3 and control cells. Single genes with the strongest association to RBM3 were further selected by gene set enrichment analysis, and their prognostic value in pancreatic cancer was examined in The Cancer Genome Atlas (TCGA). The most promising biomarker candidates with well-validated antibodies were then analyzed by immunohistochemistry in tissue microarrays with tumors from a consecutive, retrospective cohort of 175 patients with periampullary and pancreatic adenocarcinoma. Results: MIAPaCa-2 cells with downregulated RBM3 displayed 21 differentially expressed genes (p &lt; 0.01). One of the top downregulated genes was PDS cohesion associated factor A (PDS5A) encoding a protein involved in sister chromatid cohesion. PDS5A protein expression was reduced in siRBM3-treated MIAPaCa-2 cells compared to control cells. High PDS5A mRNA expression was significantly associated with a reduced survival in pancreatic cancer in the TCGA (n = 176, p = 0.026). High PDS5A protein expression in the separate cohort was significantly associated with a poor prognosis but predictive of improved response to adjuvant chemotherapy in KRAS-mutated, but not wild-type, pancreatobiliary-type tumors (p for interaction = 0.043). Conclusions: Here, we provide the first report of the expression of PDS5A in pancreatic and periampullary cancer, suggesting its potential utility as a prognostic and predictive biomarker. Further studies to unravel the underlying mechanisms are encouraged.
Monophasic Versus Biphasic Cardiac Stimulation: Mechanism of Decreased Energy Requirements (1990)

The purpose of the present study was to examine the effects of monophasic and biphasic stimulation under conditions of full and incomplete repolarization in an in vivo dog model and in an in vitro rabbit ventricular single cell model. Strength-interval curves were constructed with monophasic cathodal stimulation and biphasic subthreshold anodal followed by cathodal stimulation in dogs prior to and late after left anterior descending coronary artery occlusion. At the monophasic absolute refractory period plus 10 msec, less cathodal current was required for biphasic compared to monophasic stimulation (P = 0.04). Moreover, the biphasic absolute ventricular refractory period (116 +/- 8 msec) was significantly shorter than the monophasic absolute ventricular refractory period (136 +/- 15 msec) (P less than 0.02). At coupling intervals greater than 30 msec after the monophasic absolute ventricular refractory period, there was no distinction between monophasic and biphasic stimuli. Similarly enhanced excitability was observed with biphasic stimuli in infarcted hearts. Voltage clamp measurements mimicking conditions of the in vivo studies demonstrated that when repolarization is incomplete, a hyperpolarizing prepulse reactivates additional sodium current resulting in enhanced excitability. In conclusion, biphasic stimulation consisting of a hyperpolarizing anodal prepulse followed by a cathodal pulse decreases the current required for excitation compared to cathodal monophasic stimulation in a critical zone near the ventricular absolute refractory period.
The genetics of adiponectin. (2003)

Adiponectin encoded by the APMI gene is one of the adipocyte-expressed proteins that function in the homeostatic control of glucose, lipid, and energy metabolism. Its dysregulation has been suggested to be involved in disorders covering the metabolic X syndrome, such as insulin resistance, obesity, type 2 diabetes, and coronary artery disease. Recent data present evidence of a genetic modulation of the adiponectin level, and linkage of the 3q27 locus, where the APMI gene lies, with diabetes and features of the metabolic X syndrome playing a putative role of the APMI gene in this syndrome. In this article, we present an overview of the results available to date and discuss positive evidence for a role of genetic variants of the APMI gene and questions that genetic data raise.
Validation environment of engine health monitoring algorithms (2012)

Writing algorithms for turbofan engine health monitoring (HM or EHM) is a complex process which begins from system analysis to code writing, embedding and certification. One of those steps is the maturation stage which goal is to build and validate a prototype application (from TRL 2 to 6 [1]). Such prototype is essentially an assembly of small algorithmic pieces of codes, mainly originated by research at university labs. The validation of a prototype includes the reception, integration and a minimal industrialization of codes to ensure persistence and robustness. In this article we present our way to implement a HM validation process in Snecma which is a major player in turbofan engines manufacturing business.
Progressive cut (2006)

Recently, interactive image cutout technique becomes prevalent for image segmentation problem due to its easy-to-use nature. However, most existing stroke-based interactive object cutout system did not consider the user intention inherent in the user interaction process. Strokes in sequential steps are treated as a collection rather than a process, and only the color information of the additional stroke is used to update the color model in the graph cut framework. Accordingly, unexpected fluctuation effect may occur during the process of interactive object cutout. In fact, each step of user interaction reflects the user's evaluation of previous result and his/her intention. By analyzing the user's intention behind the interaction, we propose a progressive cut algorithm, which explicitly models the user's intention into a graph cut framework for the object cutout task. Three aspects of user intention are utilized: 1) the color of the stroke indicates the kind of change s/he expects, 2) the location of the stroke indicates the region of interest, 3) the relative position between the stroke and the previous result indicates the segmentation error. By incorporating such information into the cutout system, the new algorithm removes the unexpected fluctuation effect of existing stroke-based graph-cut methods, and thus provides the user a more controllable result with fewer strokes and faster visual feedback. Experiments and user study show the strength of progressive cut in accuracy, speed, controllability, and user experience.
Systemic mycosis due to trichosporon cutaneum a report of two additional cases (1980)

Two additional cases of systemic mycosis due to Trichosporon cutaneum are reported and are compared with the previously published case of Rivera and Cangir. Both patients (a four-year-old male and a 57-year-old female) had acute leukemia for which they were receiving chemotherapy, and both presented with fever that was unresponsive to conventional antibiotics. Both had positive blood cultures for Trichosporon cutaneum. The disease was further documented in the four-year-old male by renal biopsy and by bone marrow culture; he was treated with apparent success with amphotericin B. However, the 57-year-old female died shortly after the begining of similar treatment, and autopsy demonstrated involvement of the left kidney, spleen, bone marrow, and liver. The organism in both these cases, as well as the case of Rivera and Cangir, exhibited both hyphal and yeastlike forms in tissue sections. We believe that the therapeutic success in the case of the four-year-old male was primarily related to his remission from leukemia.
[Analysis for 6-methyladenine modification of DNA in chorionic tissue from aborted fetuses with monosomy 21]. (2020)

The 6mA modification of human genes may play a similar role to 5-methylcytosine (5mC) modification during the growth and development of embryos.
Stimuli-Responsive Reversible Two-Level Adhesion from a Structurally Dynamic Shape-Memory Polymer (2016)

A shape-memory adhesive has been prepared that exhibits two levels of reversible adhesion. The adhesive is a semicrystalline cross-linked polymer that contains dynamic disulfide bonds. Melting of the crystalline regions via heat causes a drop in the modulus of the material facilitating wetting of the substrate as well as enhancing the surface contact area with the substrate, which result in the formation of an adhesive bond. Exposure to higher heat or UV light results in dynamic exchange of the disulfide bonds, which yields a further drop in the modulus/viscosity that improves surface wetting/contact and strengthens the adhesive bond. This improvement in adhesion is shown to apply over different substrates, contact forces, and deformation modes. Furthermore, the adhesive acts as a thermal shape-memory material and can be used to create joints that can reposition themselves upon application of heat.
Spectral Shaping in Long Haul Optical Coherent Systems With High Spectral Efficiency (2014)

One of the main obstacles faced when decreasing channel spacing in optical wavelength division multiplexing (WDM) systems is the linear crosstalk resulting from spectral overlap between neighboring channels. Methods of reducing channel bandwidth and corresponding crosstalk using optical pre-filtering are reviewed along with the limitations of these techniques. High speed transmitter side digital signal processing (DSP) and digital-to-analog converters enable the use of more powerful techniques that precisely shape and limit the bandwidth of the transmitted optical signal. These techniques allow channel spacing to be reduced to nearly the theoretical minimum Nyquist spacing with only negligible crosstalk penalty. We review well known principles of linear modulation theory and apply them to coherent optical transmission systems to describe the desired channel transmit spectra along with the associated transmit and receive DSP. The implementation issues of a typical optical transmitter, which uses these techniques, are discussed. Experimental results of a laboratory long-haul WDM optical system using spectrally shaped PDM-16-QAM type modulation are presented demonstrating near Nyquist channel spacing on a trans-pacific length system with more than 44 terabits of capacity. We also present an additional application of these spectral shaping techniques, which can carefully expand the bandwidth of the transmitted channels to reduce non-linear transmission penalties. Experimental results show the advantages of these spectral broadening techniques and their ability to trade spectral efficiency for increased reach.
Receiver operating characteristic for a spectrogram correlator-based humpback whale detector-classifier (2012)

This paper presents recent experimental results and a discussion of system enhancements made to the real-time autonomous humpback whale detector-classifier algorithm first presented by Abbot et al. [J. Acoust. Soc. Am. 127, 2894-2903 (2010)]. In February 2010, a second-generation system was deployed in an experiment conducted off of leeward Kauai during which 26 h of humpback vocalizations were recorded via sonobuoy and processed in real time. These data have been analyzed along with 40 h of humpbacks-absent data collected from the same location during July-August 2009. The extensive whales-absent data set in particular has enabled the quantification of system false alarm rates and the measurement of receiver operating characteristic curves. The performance impact of three enhancements incorporated into the second-generation system are discussed, including (1) a method to eliminate redundancy in the kernel library, (2) increased use of contextual analysis, and (3) the augmentation of the training data with more recent humpback vocalizations. It will be shown that the performance of the real-time system was improved to yield a probability of correct classification of 0.93 and a probability of false alarm of 0.004 over the 66 h of independent test data.
The influence of blend morphology (co-continuous or sub-micrometer droplets dispersions) on the nucleation and crystallization kinetics of double crystalline polyethylene/polyamide blends prepared by reactive extrusion (2011)

International audience
Direct Coupling of Naphthalene and Sulfonimides Promoted by DDQ and Blue Light (2017)

Aromatic C–H amination chemistry has attracted significant attention as an alternative to conventional amination of aryl halides. Among C–H amination reactions, dehydrogenative coupling of arenes and N–H reagents represents an ideal transformation because prefunctionalization steps of arenes or aminating reagents are not required. Herein, we report direct C–H/N–H coupling between naphthalene and sulfonimides mediated by 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) as a photosensitizer under irradiation of blue light. Aromatic C–H amination chemistry has attracted significant attentions as an alternative of conventional amination of aryl halides. Among C–H amination reactions, dehydrogenative coupling of arenes and N–H reagents represents an ideal transformation because prefunctionalization steps of arenes or aminating reagents are not required. Herein, we report direct C–H/N–H coupling between naphthalene and sulfonimides mediated by 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) as a photosensitizer under irradiation of blue light.
Polymorphism of TNF Genes and Disease Susceptibility (2006)

Abstract Deoxyribonucleic acid (DNA) sequence variation (polymorphism) occurs commonly between individuals. Polymorphism of the TNF (encoding tumour necrosis factor) gene region has been implicated in defining susceptibility to many infectious, inflammatory and autoimmune diseases.
Electron exchange between ferrocene and ferrocenium ion. Effects of solvent and of ring substitution on the rate (1980)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTElectron exchange between ferrocene and ferrocenium ion. Effects of solvent and of ring substitution on the rateEdward Shih Yang, Man-Sheung Chan, and Arthur C. WahlCite this: J. Phys. Chem. 1980, 84, 23, 3094–3099Publication Date (Print):November 1, 1980Publication History Published online1 May 2002Published inissue 1 November 1980https://pubs.acs.org/doi/10.1021/j100460a025https://doi.org/10.1021/j100460a025research-articleACS PublicationsRequest reuse permissionsArticle Views1939Altmetric-Citations117LEARN 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 options Get e-Alerts