gebhart/patrepeval huggingface dataset:
Class I Histone Deacetylase Inhibition by Tianeptinaline Modulates Neuroplasticity and Enhances Memory (2018)

Through epigenetic and other regulatory functions, the histone deacetylase (HDAC) family of enzymes has emerged as a promising therapeutic target for central nervous system and other disorders. Here we report on the synthesis and functional characterization of new HDAC inhibitors based structurally on tianeptine, a drug used primarily to treat major depressive disorder (MDD) that has a poorly understood mechanism of action. Since the chemical structure of tianeptine resembles certain HDAC inhibitors, we profiled the in vitro HDAC inhibitory activity of tianeptine and demonstrated its ability to inhibit the lysine deacetylase activity of a subset of class I HDACs. Consistent with a model of active site Zn<sup>2+</sup> chelation by the carboxylic acid present in tianeptine, newly synthesized analogues containing either a hydroxamic acid or ortho-aminoanilide exhibited increased potency and selectivity among the HDAC family. This in vitro potency translated to improved efficacy in a panel of high-content imaging assays designed to assess HDAC target engagement and functional effects on critical pathways involved in neuroplasticity in both primary mouse neurons and, for the first time, human neurons differentiated from pluripotent stem cells. Most notably, tianeptinaline, a class I HDAC-selective analogue of tianeptine, but not tianeptine itself, increased histone acetylation, and enhanced CREB-mediated transcription and the expression of Arc (activity-regulated cytoskeleton-associated protein). Systemic in vivo administration of tianeptinaline to mice confirmed its brain penetration and was found to enhance contextual fear conditioning, a behavioral test of hippocampal-dependent memory. Tianeptinaline and its derivatives provide new pharmacological tools to dissect chromatin-mediated neuroplasticity underlying memory and other epigenetically related processes implicated in health and disease.
Deep Shrinkage Convolutional Neural Network for Adaptive Noise Reduction (2017)

The noise level of an image depends on settings of an imaging device. The settings can be used to select appropriate parameters for denoising methods. But denoising methods based on deep convolutional neural networks (deep-CNN) do not have such adjustable parameters. Therefore, a deep-CNN whose training data contain limited levels of noise does not effectively restore images whose noise level is different from the training data. If the range of noise levels of training data is extended to solve the problem, the maximum performance of a produced deep-CNN is limited. To solve the tradeoff, we propose a deep-CNN that is adjustable to the noise level of the input image immediately. We use soft shrinkage for activation functions of our deep-CNN. The soft shrinkage has thresholds proportional to the noise level given by the user. We also propose an optimization method for proportionality coefficients for the thresholds of soft shrinkage. Our method optimizes the coefficients for various noise levels simultaneously. In our experiment using a test set whose noise level is from 5 to 50, the proposed method showed higher PSNR than that in the case of the conventional method using only one deep-CNN, and PSNR comparable to that in the case of the conventional method using multiple noise-level-specific CNNs.
BLIMP-1/BLMP-1 and Metastasis-Associated Protein Regulate Stress Resistant Development in Caenorhabditis elegans (2016)

Environmental stress triggers multilevel adaptations in animal development that depend in part on epigenetic mechanisms. In response to harsh environmental conditions and pheromone signals, Caenorhabditis elegans larvae become the highly stress-resistant and long-lived dauer. Despite extensive studies of dauer formation pathways that integrate specific environmental cues and appear to depend on transcriptional reprogramming, the role of epigenetic regulation in dauer development has remained unclear. Here we report that BLMP-1, the BLIMP-1 ortholog, regulates dauer formation via epigenetic pathways; in the absence of TGF-β signaling (in daf-7 mutants), lack of blmp-1 caused lethality. Using this phenotype, we screened 283 epigenetic factors, and identified lin-40, a homolog of metastasis-associate protein 1 (MTA1) as an interactor of BLMP-1 The interaction between LIN-40 and BLMP-1 is conserved because mammalian homologs for both MTA1 and BLIMP-1 could also interact. From microarray studies, we identified several downstream target genes of blmp-1: npr-3, nhr-23, ptr-4, and sams-1 Among them S-adenosyl methionine synthase (SAMS-1), is the key enzyme for production of SAM used in histone methylation. Indeed, blmp-1 is necessary for controlling histone methylation level in daf-7 mutants, suggesting BLMP-1 regulates the expression of SAMS-1, which in turn may regulate histone methylation and dauer formation. Our results reveal a new interaction between BLMP-1/BLIMP-1 and LIN-40/MTA1, as well as potential epigenetic downstream pathways, whereby these proteins cooperate to regulate stress-specific developmental adaptations.
Fuel Cells: Molecular Catalysis (2011)

Abstract Popularization of fuel cells has been impeded by the low activity of electrocatalysts for the O 2 reduction reaction that involves the four‐electron transfer step. Platinum nanoparticles have been considered the best cathode catalyst toward the reduction of O 2 by four electrons into H 2 O. However, platinum is an expensive and limited resource, and it is important to find platinum‐free catalysts. This article provides a review on the recent studies on various types of platinum‐free catalysts such as nonprecious metal nanoparticles and alloys, carbon‐based catalysts, and metal complexes, focusing on the role of structure of the catalytically active site of metal complex catalysts in the OO bond scission to produce H 2 O. Emphasis is placed on the studies on cobaltporphyrins, which have been demonstrated to serve as the catalysts for the four‐electron reduction of O 2 , especially in the forms of dicobalt cofacial porphyrins and multinuclear cobaltporphyrins. Simple metalloporphyrins with spontaneous face‐to‐face aggregation properties have also been examined as a catalyst. For practical application as fuel cell cathode catalysts, it is necessary to use metalloporphyrins dispersed on carbon particles with high surface area. We summarize the recent developments on porphyrin‐based catalysts and the attempts to prepare face‐to‐face aggregates of metalloporphyrins adsorbed dispersively on carbon black. A design principle for the active site to allow the O 2 reduction at positive potentials is proposed.
Physica Advanced Peltier System PTD 150 (pat. pent.). Making the Temperature Control with a Peltier System Accurate (2001)

Abstract A new Peltier system is introduced which offers new dimensions in temperature precision for parallel-plate and cone-and-plate measuring geometries in the temperature range from −30°C to +130°C. The use of an additional actively Peltier controlled hood (pat. pent.) reduces the temperature gradient across the sample to insignificant levels. The design allows easy access for sample loading and trimming as well as the use of inert gas or a solvent trap if necessary.
Thé vert : pas de miracles non plus (2001)

Au Japon, le cancer de l'estomac reste le cancer le plus frequent, chez les hommes et chez les femmes. Il est recommande de le depister des l'âge de 40 ans. Plusieurs facteurs dietetiques ont ete supposes avoir un role protecteur ou au contraire declenchant dans l'apparition de ce cancer. Il semble en particulier que le fait de manger des aliments tres sales (pickles, poisson sale) augmente le risque, tandis que la consommation de fruits et legumes a un effet protecteur. Le the vert, populaire au Japon, est repute protecteur. Tsubono et al. [1] ont mene une etude prospective sur les personnes vivant dans la region de Miyagi, zone rurale du Nord du Japon ou l'incidence du cancer gastrique est relativement elevee. 419 cas de cancers de l'estomac ont ete identifies entre 1984 et 1992 chez les 26 311 habitants de cette municipalite. Dans le questionnaire utilise pour l'etude, la consommation de the vert etait divisee en quatre categories, la plus elevee (cinq tasses ou plus de 100 ml par jour) representant 42 % des sujets. Cette categorie aurait pu etre subdivisee en 5 a 9 tasses/jour et 10 tasses ou plus, car des etudes plus anciennes ont trouve une reduction du risque de cancer a partir de 10 tasses par jour c'est-a-dire 1 litre de the. L'etude de Tsubono et al. n'a pas retrouve d'association entre la consommation reguliere de the vert et le risque de cancer (tableau). Les auteurs rapportent meme une legere augmentation du risque chez les personnes buvant plus de cinq tasses par jour, si on les compare aux personnes buvant moins d'une tasse par jour. Dans un commentaire, Sano et Sasako [2] notent que, dans l'etude, la consommation de the etait liee a d'autres facteurs pouvant modifier le risque de cancer : ainsi, plus les sujets buvaient de the, plus ils consommaient parallelement de legumes sales (facteur de risque) et de fruits (protecteurs). Le tabagisme etait egalement plus important chez ceux qui buvaient le plus de the. Tout ceci rend l'interpretation des resultats difficile, et les resultats apportes par les autres etudes en cours seront surement utiles. 1. Tsubono Y., et al. 2001. Green tea and the risk of gastric cancer in Japan. N Engl J Med 344 : 632-6362. Sano M., Sasako T. 2001. Green tea and gastric cancer. N Engl J Med 344 : 675-676.
Conformational analysis of some 1R,4S‐2‐arylidene‐p‐menthan‐3‐ones by 1H NMR spectroscopy and molecular simulation (2002)

Abstract Based on 1 H NMR spectral analysis combined with molecular simulation, conformational states of the cyclohexanone ring were studied for some 1 R ,4 S ‐2‐(4‐X‐benzylidene)‐ p ‐menthan‐3‐ones (X = COOCH 3 or C 6 H 5 ) in CDCl 3 and C 6 D 6 . The co‐existence of chair conformers with an axial orientation of both alkyl substituents and twist‐boat forms was established for the compounds studied at room temperature (22–23° C). The substituent X does not influence appreciably the ratio of these conformers, but the fraction of twist‐boat forms increases noticeably in benzene solutions as compared with CDCl 3 solutions. Rotameric states of the isopropyl fragment were also characterised for the compounds studied. Distinctions in conformational states for the 1 R ,4 S ‐2‐arylidene‐ p ‐menthan‐3‐ones and (−)‐menthone were revealed and are discussed. Copyright © 2002 John Wiley &amp; Sons, Ltd.
Non-contact full-field optical coherence tomography: a novel tool for in vivo imaging of the human cornea (Conference Presentation) (2017)

According to the World Health Organization (WHO), corneal diseases alongside with cataract and retinal diseases are major causes of blindness worldwide. For the 95.5% of corneal blindness cases, prevention or rehabilitation could have been possible without negative consequences for vision, provided that disease is diagnosed early. However, diagnostics at the early stage requires cellular-level resolution, which is not achieved with routinely used Slit-lamp and OCT instruments. Confocal microscopy allows examination of the cornea at a resolution approaching histological detail, however requires contact with a patient’s eye. The recently developed full-field OCT technique, in which 2D en face tangential optical slices are directly recorded on a camera, was successfully applied for ex vivo eye imaging. However, in vivo human eye imaging has not been demonstrated yet. Here we present a novel non-contact full-field OCT system, which is capable of imaging in air and, therefore, shows potential for in vivo cornea imaging in patients. The first cellular-level resolution ex vivo images of cornea, obtained in a completely non-contact way, were demonstrated. We were able to scan through the entire cornea (400 µm) and resolve epithelium, Bowman’s layer, stroma and endothelium. FFOCT images of the human cornea in vivo were obtained for the first time. The epithelium structures and stromal keratocyte cells were distinguishable. Both ex vivo and in vivo images were acquired with a large (1.26 mm x 1.26 mm) field of view. Cellular details in obtained images make this device a promising candidate for realization of high-resolution in vivo cornea imaging.
Die Covid-19-Gesetzgebung im Kanton Bern (2021)

Der Kanton Bern war in der Corona-Pandemie besonders gefordert. Dies hat sich auch in den Rechtsetzungsprozessen niedergeschlagen: Sowohl beim Erlass von Notverordnungen als auch bei der Rechtsetzung des ordentlichen Verordnungsrechts bestanden zahlreiche Unklarheiten, waren in verschiedener Hinsicht Abweichungen vom üblichen Vorgehen nötig und mussten besondere und teilweise neue Wege gewählt werden, um trotz hohem Zeitdruck den institutionellen und qualitativen Anforderungen an die Rechtsetzung einerseits und den sachlichen Zwängen der Pandemie andererseits Rechnung zu tragen.
Model Transformation as Conservative Theory-Transformation. (2020)

Model transformations play a central role in model-driven software development. Hence, logical unsafe model transformation can result in erroneous systems. Still, most model transformations are written in languages that do not provide built-in safeness guarantees.
IL-18 Contributes to Host Resistance Against Infection with Cryptococcus neoformans in Mice with Defective IL-12 Synthesis Through Induction of IFN-γ Production by NK Cells (2000)

The aim of this study was to examine the contribution of IL-18 in host defense against infection caused by Cryptococcus neoformans in mice with defective IL-12 production. Experiments were conducted in mice with a targeted disruption of the gene for IL-12p40 subunit (IL-12p40-/- mice). In these mice, host resistance was impaired, as shown by increased number of organisms in both lungs and brains, compared with control mice. Serum IFN-gamma was still detected in these mice at a considerable level (20-30% of that in control mice). The host resistance was moderately impaired in IL-12p40-/- mice compared with IFN-gamma-/- mice. Neutralizing anti-IFN-gamma mAb further increased the lung burdens of organisms. In addition, treatment with neutralizing anti-IL-18 Ab almost completely abrogated the production of IFN-gamma and also impaired the host resistance. Host resistance in IL-12p40-/- IL-18-/- mice was more profoundly impaired than in IL-12p40-/- mice. Administration of IL-12 as well as IL-18 increased the serum levels of IFN-gamma and significantly restored the reduced host resistance. Spleen cells obtained from infected IL-12p40-/- mice did not produce any IFN-gamma upon restimulation with the same organisms, while those from infected and IL-12-treated mice produced IFN-gamma. In contrast, IL-18 did not show such effect. Finally, depletion of NK cells by anti-asialo GM1 Ab mostly abrogated the residual production of IFN-gamma in IL-12p40-/- mice. Our results indicate that IL-18 contributes to host resistance to cryptococcal infection through the induction of IFN-gamma production by NK cells, but not through the development of Th1 cells, under the condition in which IL-12 synthesis is deficient.
A New technique to Characterize Drilling Fluid Filter Cake (2011)

Abstract Filter cake characterization is very important in drilling and completion operations. The homogeneity of the filter cake affects the properties of filtration process such as the volume of filtrate, the thickness of filter cake, and the way to remove it. Different models were used to determine the thickness and permeability of the filter cake. These models assume that the filter cake is homogeneous. The objective of this study is to measure the filter cake thickness and permeability of water-based drilling fluids by a new approach and compare the results with previous models. A HPHT filter press was used to perform the filtration process under static conditions (225°F and 300 psi). CT (computed tomography) scan was used to measure the thickness and porosity of the filter cake. SEM was used to provide the morphology of the filter cake. Leica microscope was used to determine particle size distribution. The results obtained from the CT scan showed that the filter cake was heterogeneous and contained two layers with different properties. The average thickness of the external layer was 0.1 in., which was greater than the average thickness of the internal layer (0.06 in.). Both the porosity and permeability of the external layer were zero, while the porosity of the internal layer ranged from 10 to 20 vol. %. SEM results showed that the two layers contained large and small particles but there was a very poor sorting in the external layer, which led to zero porosity in this layer. Previous models underestimated the thickness of the filter cake by almost 50%. A new method was developed to predict the thickness and permeability of the two-layer filter cake. This method predicted the experimental data very well.
Fine Celled CFC-Free Rigid Foam - New Machinery with Low Boiling Blowing Agents (1994)

This article describes newly developed high pressure dispensing and nucleating equipment, which is designed for making fine cell foams using soluble low- boiling blowing agents (LBBA) and sparingly soluble nucleating gases, such as N 2 and no ble gases. The underlying concepts for handling, processing and metering of LBBAs have been developed from a systematic investigation of LBBA solubilities in polyols, using modelling as well as experimental measurements. In addition to the usual dispensing func tion, the equipment incorporates facilities for LBBA loading and for quantitative deter mination of dissolved and dispersed gaseous LBBA. The commercial viability of these features, under conditions simulating global industrial practice, is exemplified by present ing properties of fine-cell foams produced by using HFC-134a and HCFC-22/142b blends, in combination with tailor-made polyols, isocyanates and formulation additives.
An Energy Efficient Sub-Threshold Baseband Processor Architecture for Pulsed Ultra-Wideband Communications (2006)

This paper describes how parallelism in the digital baseband processor can reduce the energy required to receive ultra-wideband (UWB) packets. The supply voltage of the digital baseband is lowered so that the correlator operates near its minimum energy point resulting in a 68% energy reduction across the entire baseband. This optimum supply voltage occurs below the threshold voltage, placing the circuit in the sub-threshold region. The correlator and the rest of the baseband must be parallelized to maintain throughput at this reduced voltage. While sub-threshold operation is traditionally used for low energy, low frequency applications such as wrist-watches, this paper examines how sub-threshold operation can be applied to low energy, high performance applications. The correlators are further parallelized for a 31x reduction in the synchronization time, which along with duty-cycling, lowers the energy per packet by 43% for a 500 byte packet. Simulation results for a 100 Mbps UWB baseband processor are described
An Integrated Programmable High-Voltage Bipolar Pulser With Embedded Transmit/Receive Switch for Miniature Ultrasound Probes (2019)

This letter presents a compact programmable high-voltage (HV) pulser for ultrasound imaging, designed for driving capacitive micromachined ultrasonic transducers (CMUTs) in miniature ultrasound probes. To enable bipolar return-to-zero (RZ) pulsing and embedded transmit/receive switching, a compact back-to-back isolating HV switch is proposed that employs HV 'boating-gate drivers with only one HV MOS transistor each. The pulser can be digitally programmed to generate bipolar pulses with and without RZ, with a peak-to-peak swing up to 60 V, as well as negative and positive unipolar pulses. It can generate bursts of up to 63 pulses, with a maximum pulse frequency of 9 MHz for an 18-pF transducer capacitance. Realized in TSMC 0.18-μm HV BCD technology, the pulser occupies only 0.167 mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . Electrical characterization results of the pulser, as well as acoustic results obtained in the combination with a 7.5-MHz CMUT transducer, are presented.
Get Rich Quick or Get Rich Forever? (2012)

The Internet is awash with get-rich-quick schemes. But why do people believe it's possible to get rich quickly with little effort? Could the UK government be partly to blame? The widespread advertising that encourages us to buy lottery tickets focuses on showing us how we can instantly have a millionaire lifestyle without putting in any hard work. These ads do not warn of the psychological problems that can be caused by becoming so wealthy overnight, or that the odds of winning are 14 million to 1. You are 305 times more likely to get struck by lightning! When we encourage people to gamble rather than invest, we are preying on people's inherent laziness. Why not show them a way to earn a million through hard work, as opposed to win a million through luck? There are no guaranteed (legal) get-rich-quick plans available—anywhere. If it were easy and quick to get rich, everyone would do it; it takes hard work and a long time to build wealth. The authors stress that the Wealth Dragons' ethos is 100 percent founded in the need to take action and work hard in order to build wealth.
Vitamin D receptor agonist paricalcitol plus gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer. (2020)

TPS784 Background: Patients(pts) with metastatic pancreatic cancer (PC) have a median survival of less than one year even with use of multiagent chemotherapy programs. Pancreatic tumors are composed of multiple cell types and a dense extracellular matrix that may support cancer cell proliferation and impede chemotherapy delivery. Cancer-associated fibroblasts (CAF’s) in the tumor microenvironment secrete pro-inflammatory factors and components of the extracellular matrix. In PC laboratory models, engagement of the vitamin D receptor (VDR) by VDR agonists shifts CAFs toward a more quiescent phenotype with reduced tumor growth and improved chemotherapy penetration (Sherman. Cell, 2014). Paricalcitol is a synthetic VDR agonist used in patients with secondary hyperparathyroidism due to chronic kidney disease. A prior pilot study evaluated IV paricalcitol with gemcitabine (G) and nab-paclitaxel (A) before surgical resection in patients with resectable PC (NCT02030860). Methods: Pts with previously-untreated metastatic PC will be enrolled in a two-stage study consisting of a safety run-in and a randomized phase 2 study (NCT03520790). In the run-in stage, 36 pts will be randomized 1:1:1 to G (1000 mg/m 2 ) and A (125 mg/m 2 ) given 3 weeks on and 1 week off plus: (a) paricalcitol 25mcg IV thrice weekly, (b) paricalcitol 16mcg oral daily, or (c) placebo oral daily. Grade 3/4 hypercalcemia or genitourinary stones will be considered dose limiting toxicities.Pts will undergo paired pre- and on-treatment tumor biopsies to examine pharmacodynamic (PD) markers by bulk and single cell RNA sequencing and multiplex immunofluoresence.Assuming safety and supportive PD assessments, the phase 2 study will randomize an additional 76 pts to two treatment arms with GA plus: (a) paricalcitol or (b) placebo.Paricalcitol formulation (IV or oral) will be determined based on data from the run-in stage.The primary endpoint of the phase 2 study is overall survival, with a total of 100 pts needed to identify a hazard ratio of 0.6 with 80% power and one-sided alpha of 0.10.Secondary endpoints include safety, response rate, and progression free survival.Trial funding provided by SU2C, CRUK,Lustgarten Foundation, and AACR. Clinical trial information: NCT03520790.