gebhart/patrepeval huggingface dataset:
The selective glucocorticoid receptor antagonist CORT125281 has tissue-specific activity (2020)

Glucocorticoids mediate numerous essential processes in the human body via binding to the glucocorticoid receptor (GR). Excessive GR signaling can cause disease, and GR antagonists can be used to treat many symptoms of glucocorticoid-induced pathology. The purpose of this study was to characterize the tissue-specific properties of the selective GR antagonist CORT125281. We evaluated the antagonistic effects of CORT125281 upon acute and subchronic corticosterone exposure in mice. In the acute corticosterone setting, hypothalamus-pituitary-adrenal-axis activity was investigated by measurement of basal- and stress-induced corticosterone levels, adrenocorticotropic hormone levels and pituitary proopiomelanocortin expression. GR signaling was evaluated by RT-PCR analysis of GR-responsive transcripts in liver, muscle, brown adipose tissue (BAT), white adipose tissue (WAT) and hippocampus. Pretreatment with a high dose of CORT125281 antagonized GR activity in a tissue-dependent manner. We observed complete inhibition of GR-induced target gene expression in the liver, partial blockade in muscle and BAT and no antagonism in WAT and hippocampus. Tissue distribution only partially explained the lack of effective antagonism. CORT125281 treatment did not disinhibit the hypothalamus-pituitary-adrenal neuroendocrine axis. In the subchronic corticosterone setting, CORT125281 partially prevented corticosterone-induced hyperinsulinemia, but not hyperlipidemia and immune suppression. In conclusion, CORT125281 antagonizes GR transcriptional activity in a tissue-dependent manner and improves corticosterone-induced hyperinsulinemia. Tailored dosing of CORT125281 may allow tissue-specific inhibition of GR transcriptional activity.
Interactions betweenHelicobacter pyloriand the Local Mucosal Immune System (1991)

The recognition that Helicobacter pylori is associated with an array of gastric disorders immediately raises several issues with regard to the role of the local immune system. The belief that the harsh gastric environment limits or prevents infection has perhaps dismissed studies into the immunology of the stomach as a low priority. Now, in combination with our understanding of local immune reactivity in pernicious anaemia, an interest in defining the contribution of the immune response in the pathogenesis of disease associated with H. pylori has fueled a great deal of interest. Furthermore, the evidence of local immunity to this bacteria has kindled interest that gastric immune/inflammatory responses may contribute to the treatment or prevention of a gastric infection.
Electrical activation of degenerated photoreceptors in blind mouse retina elicited network-mediated responses in different types of ganglion cells (2018)

Electrical (e-) stimulation is explored in schemes to rescue the vision of blind people, e.g. those affected by Retinitis Pigmentosa (RP). We e-activated subretinally the surviving degenerated photoreceptors (d-Phrs) of the rd1 mouse (RP model) and evoked visual responses in the blind retina. The e-stimulation was applied with a single platinum/iridium electrode. The d-Phrs (calcium-imaging) and ganglion cells (GC) activity (MEA-recording) were recorded in simultaneous multilayer recordings. The findings of this study confirm that the d-Phrs responded to e-stimulation and modulated the retinal network-activity. The application of blockers revealed that the synaptic interactions were dependent on voltage-gated calcium channels and mediated by the transmitters glutamate and GABA. Moreover, the gap junctions coupled networks promoted the lateral-spread of the e-evoked activity in the outer (~60 µm) and inner (~120 µm) retina. The activated GCs were identified as subtypes of the ON, OFF and ON-OFF classes. In conclusion, d-Phrs are the ideal interface partners for implants to elicit enhanced visual responses at higher temporal and spatial resolution. Furthermore, the retina's intact circuity at the onset of complete blindness makes it a tempting target when considering the implantation of implants into young patients to provide a seamless transition from blinding to chip-aided vision.
Inferring mechanisms of response prioritization on social media under information overload (2021)

Human decision-making is subject to the biological limits of cognition. The fluidity of information propagation over online social media often leads users to experience information overload. This in turn affects which information received by users are processed and gain a response to, imposing constraints on volumes of, and participation in, information cascades. In this study, we investigate properties contributing to the visibility of online social media notifications by highly active users experiencing information overload via cross-platform social influence. We analyze simulations of a coupled agent-based model of information overload and the multi-action cascade model of conversation with evolutionary model discovery. Evolutionary model discovery automates mechanistic inference on agent-based models by enabling random forest importance analysis on genetically programmed agent-based model rules. The mechanisms of information overload have shown to contribute to a multitude of global properties of online information cascades. We investigate nine characteristics of online messages that may contribute to the prioritization of messages for response. Our results indicate that recency had the largest contribution to message visibility, with individuals prioritizing more recent notifications. Global popularity of the conversation originator had the second highest contribution, and reduced message visibility. Messages that presented opportunity for novel user interaction, yet high reciprocity showed to have relatively moderate contribution to message visibility. Finally, insights from the evolutionary model discovery results helped inform response prioritization rules, which improved the robustness and accuracy of the model of information overload.
The Use of Copper as the Retaining Ion in the Elution of Rare Earths with Ammonium Ethylenediamine Tetraacetate Solutions (1954)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe Use of Copper as the Retaining Ion in the Elution of Rare Earths with Ammonium Ethylenediamine Tetraacetate SolutionsF. H. Spedding, J. E. Powell, and E. J. WheelwrightCite this: J. Am. Chem. Soc. 1954, 76, 9, 2557–2560Publication Date (Print):May 1, 1954Publication History Published online1 May 2002Published inissue 1 May 1954https://pubs.acs.org/doi/10.1021/ja01638a075https://doi.org/10.1021/ja01638a075research-articleACS PublicationsRequest reuse permissionsArticle Views185Altmetric-Citations46LEARN 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
The potential of cryo-electron microscopy for structure-based drug design (2017)

Structure-based drug design plays a central role in therapeutic development. Until recently, protein crystallography and NMR have dominated experimental approaches to obtain structural information of biological molecules. However, in recent years rapid technical developments in single particle cryo-electron microscopy (cryo-EM) have enabled the determination to near-atomic resolution of macromolecules ranging from large multi-subunit molecular machines to proteins as small as 64 kDa. These advances have revolutionized structural biology by hugely expanding both the range of macromolecules whose structures can be determined, and by providing a description of macromolecular dynamics. Cryo-EM is now poised to similarly transform the discipline of structure-based drug discovery. This article reviews the potential of cryo-EM for drug discovery with reference to protein ligand complex structures determined using this technique.
A 7 mW 20 MHz BW Time-Encoding Oversampling Converter Implemented in a 0.08 mm$^{2}$ 65 nm CMOS Circuit (2011)

This work presents an area- and power-efficient realization of a new time-encoding oversampling converter (TEOC) consisting of a third-order continuous time (CT) loop filter and a self-oscillating pulse-width modulator (PWM). The modulator displays similar performance to that of a standard multibit CT-ΣΔ modulator but has the complexity of a single bit design. The time-encoding quantizer (TEQ) is implemented inside a ΣΔ modulator by replacing a multibit quantizer. An innovative TEQ is used to overcome design issues in a 1.0 V supply-voltage 65 nm digital CMOS technology. The TEQ allows an exchange of amplitude-resolution by time-resolution. The approach of time-resolution alleviates the scaling difficulties of mixed-signal circuits in nano-scale technologies. The TEOC features a 63 dB dynamic-range and a peak-SNDR of 61 dB over a 20 MHz signal bandwidth. Clocked at 2.5 GHz, the complete ADC consumes 7 mW from a single 1.0 V supply, including also the reference buffers. The ADC core results in an attractively small area of 0.08 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and in a figure-of-merit (FoM=Pwr/2 · BW · 2 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">ENOB</sup> ) of 0.17 pJ/conversion-step.
Gradient-descent-based learning in memristive crossbar arrays (2015)

This paper describes techniques to implement gradient-descent-based machine learning algorithms on crossbar arrays made of memristors or other analog memory devices. We introduce the Unregulated Step Descent (USD) algorithm, which is an approximation of the steepest descent algorithm, and discuss how it addresses various hardware implementation issues. We discuss the effect of device parameters and their variability on performance of the algorithm by using artificially generated and real-world datasets. In addition to providing insights on the effect of device parameters on learning, we illustrate how the USD algorithm partially offsets the effect of device variability. Finally, we discuss how the USD algorithm can be implemented in crossbar arrays using a simple 4-phase training scheme. The method allows parallel update of crossbar memory elements and reduces the hardware cost and complexity of the training architecture significantly.
A role of accelerator-driven reactor to meet future energy demands (1998)

Fissile fuel can be produced at a high rate using an accelerator driven Pu fueled fast reactor operated at deep subcriticality; this approach avoids encountering a shortage of Pu during a high rate of growth in the production of nuclear energy. Slightly reducing the acceleration field minimizes the tripping of the beam and the radiation dose from the accelerator; hence the accelerator can be operated as a highly reliable industrial machine. The usefulness of a windowless liquid jet target, which eliminates the spreading of the beam and problems of radiation damage is emphasized, in association with the small size of the target. The requirements for a proton beam accelerator for this system are discussed.
True 2D wavelength division multiplexing, binary superimposed gratings and their applications (1998)

grantor: University of Toronto
A Career in Toxicology (1996)

Over the past two decades, deadly coronaviruses, with the most recent being the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) 2019 pandemic, have majorly challenged public health. The path for virus invasion into humans and other ...Read More
A process/device/circuit/system compatible simulation framework for poly-Si TFT based SRAM design (2013)

Operation characteristics of low temperature poly silicon thin-film transistor (LTPS-TFT) based systems vary significantly with design choices and parameters (i.e., process, device, circuit and system). Due to the lack of cross-layer simulation tool, conventional designs only optimize the design layers in isolation, leading to sub-optimal solutions. We present a cross-layer simulation framework for the design of LTPS-TFT Static Random Access Memory (SRAM). The proposed simulation framework optimizes design parameters considering the entire design space and hence, greatly reduces design complexity and efforts. The benefits of our proposed framework are illustrated by case studies.
Influence of Isotherm Inflection on the Loading Dependence of the Diffusivities of n-Hexane and n-Heptane in MFI Zeolite. Quasi-Elastic Neutron Scattering Experiments Supplemented by Molecular Simulations (2006)

Quasi-Elastic Neutron Scattering (QENS) experiments were carried out to determine (a) Fick diffusivity, D (b) self-diffusivity, Dself, and (c) 1/Gamma, the inverse of the thermodynamic correction factor, for n-hexane (nC6) and n-heptane (nC7) in MFI zeolite (all silica silicalite-1) at 300 K for a variety of loadings. These experimental results are compared with configurational-bias Monte Carlo (CBMC) and molecular dynamics (MD) simulations of, respectively, the adsorption isotherms and diffusivities. For n-hexane, the CBMC simulated isotherm shows a slight inflection at a loading=4 molecules per unit cell; this inflection manifests, also, in the loading dependence of 1/Gamma, obtained from QENS. The trend in the loading dependence of the Fick D and Dself of nC6 obtained from QENS matches the MD simulation results. For nC7 the CBMC simulated isotherm shows a strong inflection at a loading=4 molecules per unit cell. At this loading=4, 1/Gamma tends to zero and there is a very good match between QENS and molecular simulations for the loading dependence of 1/Gamma. Both MD simulations and QENS data on the Fick diffusivity shows a sharp maximum at a loading in the region of=4. For both nC6 and nC7 the simulated values of diffusivity are about an order of magnitude higher than those determined from QENS.
RotationNet: Learning Object Classification Using Unsupervised Viewpoint Estimation. (2016)

The recent popularization of depth sensors and the availability of large-scale 3D model databases such as ShapeNet have drawn increased attention to 3D object recognition. Despite the convenience of using 3D models captured offline, we are allowed to observe only a single view of an object at once, with the exception of the use of special environments such as multi-camera studios. This impedes the recognition of diverse objects in a real environment. If a mechanical system (or a robot) has access to multi-view models of objects and is able to estimate the viewpoint of a currently observed object, it can rotate the object to a better view for classification. In this paper, we propose a novel method to learn a deep convolutional neural network that both classifies an object and estimates the rotation path to its best view under the predicted object category. We conduct experiments on a 3D model database as well as a real image dataset to demonstrate that our system can achieve an effective strategy of object rotation for category classification.
Appraisal of a manual blunt dissection for an intraoperative diagnosis of extrahepatic cancer invasion. (1999)

An accurate intraoperative diagnosis of extrahepatic cancer invasion can be made using manual blunt dissection.
Dose-effect relationship of idebenone in an experimental cerebral deficit model. Pilot study in healthy young volunteers with piracetam as reference drug. (1998)

Within a general cerebral deficit model--inspiratory hypoxia-the dose--effect relationship of idebenone (CAS 58186-27-9), an antioxidant, was studied with regard to selected electrophysiological and psychometric parameters. Seventeen healthy male volunteers (mean age = 32 years, mean BW = 75 kg) received three different oral medications: placebo, idebenone and piracetam (CAS 7491-74-9) as reference. The test drug idebenone was administered in five different dosages, ranging--in 60 mg steps--from 60 to 300 mg t.id. Piracetam was given at a dose level of 800 mg t.i.d. A strict dose-regimen was used in idebenone for safety reasons. Each dosage/medication--except idebenone 300 mg t.i.d.--was given for one week without washouts in between. On each 7th treatment day, pharmacodynamic assessments comprising electroretinography (ERG), auditory evoked potentials (AEP) and visual analogue scales (VAS) were run. Immediately after the phases with the lower dosages, the study was continued with the highest dosage of idebenone (300 mg t.i.d.) for a period of four weeks with pharmacodynamic assessments on the 7th, 14th and 28th day. In this pilot study, the target variable, the amplitude of the ERG b-wave indicated a definite antihypoxidotic effect after the highest dosage of idebenone. With 300 mg idebenone t.i.d., ERG b-wave amplitudes increased linearily with increasing duration of treatment. The 'central' AEP P2-amplitude demonstrated a different dose-effect relationship. AEP P2-amplitudes increased with increasing dosages of idebenone. The prolongation of treatment with 300 mg t.i.d. resulted in no further improvement of this parameter (ceiling effect). Subjective ratings (VAS) by the volunteers confirmed the results seen in electrophysiological variables. The findings, however, remain to be confirmed within an adequate double-blind, crossover study design.
A microsensor for hydroquinone and catechol based on a poly(3,4-ethylenedioxythiophene) modified carbon fiber electrode (2015)

A microsensor for hydroquinone and catechol was constructed based on a carbon fiber electrode modified by poly(3,4-ethylenedioxythiophene) by several simple steps. This microsensor exhibited excellent electrochemical activity toward the oxidation of the two diphenol isomers, and satisfying results were obtained.
Overexpression of F-Box Nictaba Promotes Defense and Anthocyanin Accumulation in Arabidopsis thaliana After Pseudomonas syringae Infection (2021)

<i>Pseudomonas syringae</i> pv. <i>tomato</i> DC3000 (<i>Pst</i> DC3000) is a well-known pathogen and model organism used to study plant-pathogen interactions and subsequent plant immune responses. Numerous studies have demonstrated the effect of <i>Pst</i> DC3000 on <i>Arabidopsis</i> plants and how type III effectors are required to promote bacterial virulence and pathogenesis. F-Box Nictaba (encoded by <i>At2g02360</i>) is a stress-inducible lectin that is upregulated in <i>Arabidopsis thaliana</i> leaves after <i>Pst</i> DC3000 infection. In this study, a flood inoculation assay was optimized to check the performance of transgenic <i>Arabidopsis</i> seedlings with different expression levels of F-Box Nictaba after bacterial infection. Using a combination of multispectral and fluorescent imaging combined with molecular techniques, disease symptoms, transcript levels for F-Box Nictaba, and disease-related genes were studied in <i>Arabidopsis</i> leaves infected with two virulent strains: <i>Pst</i> DC3000 and its mutant strain, deficient in flagellin Δ<i>fliC</i>. Analyses of plants infected with fluorescently labeled <i>Pst</i> DC3000 allowed us to study the differences in bacterial colonization between plant lines. Overexpression plants showed a reduced bacterial content during the later stages of the infection. Our results show that overexpression of F-Box Nictaba resulted in reduced leaf damage after bacterial infections, whereas knockdown and knockout lines were not more susceptible to <i>Pseudomonas</i> infection than wild-type plants. In contrast to wild-type and knockout plants, overexpressing lines for F-Box Nictaba revealed a significant increase in anthocyanin content, better efficiency of photosystem II (Fv/Fm), and higher chlorophyll content after <i>Pst</i> DC3000 infection. Overexpression of F-Box Nictaba coincided with increased expression of salicylic acid (SA) related defense genes, confirming earlier data that showed that F-Box Nictaba is part of the SA-dependent defense against <i>Pst</i> DC3000 infection. Knockout lines yielded no discernible effects on plant symptoms after <i>Pseudomonas</i> infection suggesting possible gene redundancy between F-Box Nictaba genes.
Role of radiation therapy in the treatment of carcinoma of the rectum (1991)

Radiation therapy has assumed an integral role in the treatment of rectal carcinoma. The major role is in the surgical adjuvant setting in which the addition of radiation therapy can decrease the risk of local failure from up to 50% for stages B2 and C, to approximately 20%. The addition of sensitizing chemotherapy may add further benefit. Anal sphincter conservation is possible in another subset of patients with localized rectal carcinoma. Local excision and radiation therapy can achieve up to 90% local control, providing an attractive alternative to traditional ablative treatment. The other group of patients who benefited are those with locally advanced disease in whom a curative operative procedure cannot be performed. Radiation therapy can render greater than 50% of these patients operable and lead to about 25% long term local control.
Characterization of a Root-Specific Arabidopsis Terpene Synthase Responsible for the Formation of the Volatile Monoterpene 1,8-Cineole (2004)

Arabidopsis is emerging as a model system to study the biochemistry, biological functions, and evolution of plant terpene secondary metabolism. It was previously shown that the Arabidopsis genome contains over 30 genes potentially encoding terpene synthases (TPSs). Here we report the characterization of a monoterpene synthase encoded by two identical, closely linked genes, At3g25820 and At3g25830. Transcripts of these genes were detected almost exclusively in roots. An At3g25820/At3g25830 cDNA was expressed in Escherichia coli, and the protein thus produced was shown to catalyze the formation of 10 volatile monoterpenes from geranyl diphosphate, with 1,8-cineole predominating. This protein was therefore designated AtTPS-Cin. The purified recombinant AtTPS-Cin displayed similar biochemical properties to other known monoterpene synthases, except for a relatively low K(m) value for geranyl diphosphate of 0.2 microm. At3g25820/At3g25830 promoter activity, measured with a beta-glucuronidase (GUS) reporter gene, was primarily found in the epidermis, cortex, and stele of mature primary and lateral roots, but not in the root meristem or the elongation zone. Although the products of AtTPS-Cin were not detected by direct extraction of plant tissue, the recent report of 1,8-cineole as an Arabidopsis root volatile (Steeghs M, Bais HP, de Gouw J, Goldan P, Kuster W, Northway M, Fall R, Vivanco JM [2004] Plant Physiol 135: 47-58) suggests that the enzyme products may be released into the rhizosphere rather than accumulated. Among Arabidopsis TPSs, AtTPS-Cin is most similar to the TPS encoded by At3g25810, a closely linked gene previously shown to be exclusively expressed in flowers. At3g25810 TPS catalyzes the formation of a set of monoterpenes that is very similar to those produced by AtTPS-Cin, but its major products are myrcene and (E)-beta-ocimene, and it does not form 1,8-cineole. These data demonstrate that divergence of organ expression pattern and product specificity are ongoing processes within the Arabidopsis TPS family.