gebhart/patrepeval huggingface dataset:
Activation of the CAMP signaling pathway increases apoptosis in human B‐precursor cells and is associated with downregulation of Mcl‐1 expression (1999)

During B- and T-cell ontogeny, extensive apoptosis occurs at distinct stages of development. Agents that increase intracellular levels of cAMP induce apoptosis in thymocytes and mature B cells, prompting us to investigate the role of cAMP signaling in human CD10+ B-precursor cells. We show for the first time that forskolin (which increases intracellular levels of cAMP) increases apoptosis in the CD10+ cells in a dose-dependent manner (19%–94% with 0–1,000 μM forskolin after 48 hours incubation, IC50 = 150 μM). High levels of apoptosis were also obtained by exposing the cells to the cAMP analogue 8-chlorophenylthio-cAMP (8-CPT-cAMP). Specific involvement of cAMP-dependent protein kinase (PKA) was demonstrated by the ability of a cAMP antagonist, Rp-isomer of 8-bromo-adenosine- 3′, 5′- monophosphorothioate (Rp-8-Br-cAMPS), to reverse the apoptosis increasing effect of the complementary cAMP agonist, Sp-8-Br-cAMPS. Furthermore, we investigated the expression of Bcl-2 family proteins. We found that treatment of the cells with forskolin or 8-CPT-cAMP for 48 hours resulted in a fourfold decline in the expression of Mcl-1 (n = 6, P = 0.002) compared to control cells. The expression of Bcl-2, Bcl-xl, or Bax was largely unaffected. Mature peripheral blood B cells showed a smaller increase in the percentage of apoptotic cells in response to 8-CPT-cAMP (1.3-fold, n = 6, P = 0.045) compared to B-precursor cells, and a smaller decrease in Mcl-1 levels (1.5-fold, n = 4, P = 0.014). Taken together, these findings show that cAMP is important in the regulation of apoptosis in B-progenitor and mature B cells and suggest that cAMP-increased apoptosis could be mediated, at least in part, by a decrease in Mcl-1 levels. J. Cell. Physiol. 180:71–80, 1999. © 1999 Wiley-Liss, Inc.
A multi-attribute auctioning system for the circular economy with Ricardian contracts (2022)

In this paper, we define a multi-attribute auctioning system for the circular economy and the trade of products, components and materials subject to recycling. The increasing popularity of auctioning systems for buying and selling goods has led to the adaptation of them to diverse and particular scenarios, many of which require support for attributes like delivery time, quality, etc. Such attributes allow for more explicit and precise negotiations than traditional auctioning systems where only price is taken into account. The circular economy concept replaces end-of-life with the reuse of various goods, aiming to keep as much value as possible of any asset. By allowing users to adjust attributes in multi-step negotiations according to their economic and ecological needs, better deals can be achieved. We address this potential with our multi-attribute, and multi-step auctioning system. The system is based on transparency and fairness principles, and addresses requirements for flexibility in what attributes can be used, and the need for a semi-transparent auctioning procedure. We present a winner determination approach based on scoring protocol based on weights for different input attributes. Our auctioning system uses a signature chain data structure to provide transaction traceability. We demonstrate using a generic example that the proposed system supports simple and flexible multi-attribute auctions.
Asian Lineage of Peste des Petits Ruminants Virus, Africa (2011)

Interest in peste des petits ruminants virus (PPRV) has been stimulated by recent changes in its host and geographic distribution. For this study, biological specimens were collected from camels, sheep, and goats clinically suspected of having PPRV infection in Sudan during 2000-2009 and from sheep soon after the first reported outbreaks in Morocco in 2008. Reverse transcription PCR analysis confirmed the wide distribution of PPRV throughout Sudan and spread of the virus in Morocco. Molecular typing of 32 samples positive for PPRV provided strong evidence of the introduction and broad spread of Asian lineage IV. This lineage was defined further by 2 subclusters; one consisted of camel and goat isolates and some of the sheep isolates, while the other contained only sheep isolates, a finding with suggests a genetic bias according to the host. This study provides evidence of the recent spread of PPRV lineage IV in Africa.
Foliar application of abscisic acid mitigates cadmium stress and increases food safety of cadmium-sensitive lettuce (Lactuca sativa L.) genotype (2020)

Cadmium (Cd<sup>2 +</sup>) is among the toxic non-essential heavy metals that adversely affect plants metabolic processes and the safety of produce. However, plant hormones can improve plant's tolerance to various stresses. This study investigated the effect of exogenous abscisic acid (ABA) on the biochemical and physiological processes and food safety of cadmium (Cd<sup>2 +</sup>)-sensitive lettuce genotype (<i>Lüsu</i>). Seedlings were subjected to five treatments: [(i) Control (untreated plants), (ii) 100 µM CdCl<sub>2</sub>, (iii) 100 µM CdCl<sub>2</sub>+10 µg L<sup>-1</sup> ABA (iv) 10 µg L<sup>-1</sup> ABA, and (v) 0.01 g L<sup>-1</sup> ABA-inhibitor (fluridone)] for fourteen days in hydroponic system. The 100 µM CdCl<sub>2</sub> increased the contents of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) and malondialdehyde (MDA), decreased photosynthesis and plant biomass. Moreover, it decreased the contents of essential nutrients (except copper) in the leaves but increased the contents of toxic Cd<sup>2 +</sup> in the leaves and roots of the plants. Foliar application of fluridone (0.01 g L<sup>-1</sup>) also caused oxidative stress by increasing the contents of H<sub>2</sub>O<sub>2</sub> and MDA. It also decreased the contents of nutrient elements in the leaves of the plants. However, exogenous ABA (10 µg L<sup>-1</sup>) mitigated the Cd<sup>2 +</sup>-induced stress, increased antioxidant enzymes activities, photosynthesis and plant biomass under CdCl<sub>2</sub> treatment. Remarkably, exogenous ABA increased the contents of essential nutrient elements but decreased the Cd<sup>2 +</sup> content in leaves under the CdCl<sub>2</sub> treatment. Our results have demonstrated that foliar application of ABA mitigates Cd<sup>2 +</sup> stress and increases the nutritional quality and food safety of Cd<sup>2 +</sup>-sensitive lettuce genotype under CdCl<sub>2</sub> treatment.
Back-gated MOSFETs with controlled silicon thickness for adaptive threshold-voltage control (2004)

Experimental results for back-gated thin silicon transistors that allow adaptive threshold-voltage control and exhibit low drain-induced-barrier-lowering due to improved electrostatics of the geometry are reported. The implementation of the back-gate is achieved by a low-temperature bonding process capable of tens of nanometre silicon channel thickness, good surface and bulk quality. The technology is compatible with mainstream silicon CMOS processing technology.
Intra-Multi-Chip Module (MCM) Optical Clock Signal Distribution (1994)

Get PDF Email Share Share with Facebook Tweet This Post on reddit Share with LinkedIn Add to CiteULike Add to Mendeley Add to BibSonomy Get Citation Copy Citation Text Suning Tang and Ray T. Chen, "Intra-Multi-Chip Module (MCM) Optical Clock Signal Distribution," Optics & Photonics News 5(12), 41_1-42 (1994) Export Citation BibTex Endnote (RIS) HTML Plain Text Citation alert Save article
In Situ Scanning Tunneling Microscopy of 1,6-Hexanedithiol, 1,9-Nonanedithiol, 1,2-Benzenedithiol, and 1,3-Benzenedithiol Adsorbed on Pt(111) Electrodes (2006)

Cyclic voltammetry (CV) and in situ scanning tunneling microscopy (STM) were used to examine four dithiol molecules, including 1,6-hexanedithiol, 1,9-nonanedithiol, 1,2-benzenedithiol, and 1,3-benzenedithiol, adsorbed on well-ordered Pt(111) electrodes in 0.1 M HClO(4). The open-circuit potential (OCP) of Pt(111) electrodes decreased substantially from 0.95 to 0.3 V (versus reversible hydrogen electrode) upon the adsorption of dithol molecules, which indicates that these adsorbates injected electrons into the Pt electrode. For all dithiol molecules, ordered adlattices of p(2 x 2) and (square root 3 x square root 3)R30 degrees were formed when the dosing concentration was lower than 150 microM and the potential of Pt(111) was more negative than 0.5 V. Raising the potential of Pt(111) from 0.1 to 0.4 V or more positive values could transform p(2 x 2) to (square root 3 x square root 3)R30 degrees before it turned disarray. The insensitivity of the structure of dithiol adlayers with their chemical structures was explained by upright molecular orientation with the formation of one Pt-S bond per dithiol molecule. This molecular orientation was independent of the coverage of dithiol molecules, as nucleation seeds produced at the beginning of adsorption were also constructed with p(2 x 2). The triangular-shaped STM molecular resolution suggested 3-fold binding of sulfur headgroup on Pt(111). All dithiols were adsorbed so strongly on Pt(111) electrodes that switching the potential negatively to the onset of hydrogen evolution in 0.1 M HClO(4) or water reduction in 1 M KOH could not displace dithiol admolecules.
The Combination of Mesyl-Phosphoramidate Inter-Nucleotide Linkages and 2′- O -Methyl in Selected Positions in the Antisense Oligonucleotide Enhances the Performance of RNaseH1 Active PS-ASOs (2022)

Antisense oligonucleotides (ASOs) that mediate RNA target degradation by RNase H1 are used as drugs to treat various diseases. Previously we found that introduction of a single 2'-<i>O</i>-methyl (2'-OMe) modification in position 2 of the central deoxynucleotide region of a gapmer phosphorothioate (PS) ASO, in which several residues at the termini are 2'-methoxyethyl, 2' constrained ethyl, or locked nucleic acid, dramatically reduced cytotoxicity with only modest effects on potency. More recently, we demonstrated that replacement of the PS linkage at position 2 or 3 in the gap with a mesyl-phosphoramidate (MsPA) linkage also significantly reduced toxicity without meaningful loss of potency and increased the elimination half-life of the ASOs. In this study, we evaluated the effects of the combination of MsPA linkages and 2'-OMe nucleotides on PS ASO performance. We found that two MsPA modifications at the 5' end of the gap or in the 3'-wing of a Gap 2'-OMe PS ASO substantially increased the activity of ASOs with OMe at position 2 of the gap without altering the safety profile. Such effects were observed with multiple sequences in cells and animals. Thus, the MsPA modification improves the RNase H1 cleavage rate of PS ASOs with a 2'-OMe in the gap, significantly reduces binding of proteins involved in cytotoxicity, and prolongs elimination half-lives.
Fabrication and Evaluation of CrSi2/NbSi2 Composites. (1999)

CrSi2 based composites were fabricated by the pulse electric current sintering (PECS) technique and normal sintering technique. The sintering behaviors for these CrSi2 based composites were mainly investigated. The dense CrSi2 based composites with the addition of 5-50mol%NbSi2 were obtained at 1100°C by PECS technique, although not by the normal sintering technique even at 1400°C. Furthermore the relative densities of CrSi2/NbSi2 composites prepared by the PECS decreased with the sintering temperature. Young's modulus for these CrSi2/NbSi2 composites was evaluated. The microstructure of these CrSi2/NbSi2 composites was observed mainly by scanning electron microscopy. NbSi2 particles were homogeneously dispersed in the CrSi2 matrix.
Use of Clinical Trial Simulations to Compare the Performance of Different Approaches for Population Analyses of Pediatric Pharmacokinetic Data (2023)

The adequate characterization of the pharmacokinetics of a drug used in pediatrics is a mainstay of pediatric development programs and is critical for accurate dose selection in pediatrics. Analysis approaches can impact the estimation and characterization of pediatric pharmacokinetic parameters. Simulations were conducted to compare the performance of different approaches for analyzing pediatric pharmacokinetic data in the presence of extensive data from adult studies. Simulated clinical trial datasets were generated encompassing different scenarios that might be encountered in pediatric drug development. For each scenario, 250 clinical trials were simulated and analyzed using each of the following approaches: (1) estimating pediatric parameters using only pediatric data; (2) fixing specific parameters to adult estimates and estimating the remaining pediatric parameters using only pediatric data; (3) estimating pediatric parameters using adult parameters as informative Bayesian priors; (4) estimating pediatric parameters using combined adult and pediatric datasets with exponents for body weight effects estimated using adult and pediatric data; and (5) estimating pediatric parameters using combined adult and pediatric datasets with exponents for body weight effects estimated using pediatric data only. Each analysis approach was evaluated for its success in the estimation of true pediatric pharmacokinetic parameter values. Results demonstrated that analyzing pediatric data using a Bayesian approach generally performed best and had the lowest probability of significant bias in the estimated pediatric pharmacokinetic parameters among different scenarios evaluated. This clinical trial simulation framework can be used to inform the optimal approach for analyses of pediatric data for other pediatric drug development program scenarios beyond the cases evaluated in these analyses.
[Mildronate in geriatric patients with cardiac failure]. (2006)

Elderly patients tolerated mildronate well. It was a safe drug attenuating CF symptoms, increasing exercise tolerance and improving quality of life.
Analysis of capacitive power transfer GaN ISOP multi-cell DC/DC converter systems for single-phase telecom power supply modules (2016)

The Input Series Output Parallel (ISOP) multi-cell converter approach allows breaking the performance barriers of conventional single-cell telecom rectifier systems by leveraging the advantages of using multiple interleaved low-voltage and/or low-current converter cells. The ISOP interconnection in the DC/DC converter part of the cells, however, requires the employment of some kind of isolation in each cell, which is typically provided by transformers. An analysis of the losses and of the volume of the entire multi-cell system reveals that these transformers contribute a major part to the system losses and are responsible for a significant share of the total volume. However, as the transformers are mainly required for providing galvanic isolation in the ISOP structure and not for voltage conversion, series capacitors represent an alternative to decouple the series connected input terminals of the cells from the parallel connected output terminals. Compared to conventional solutions with transformers, the resulting capacitive power transfer ISOP multi-cell DC/DC converter (CPT-ISOP-MCC) system features lower losses and a smaller volume. In this paper, the benefits as well as the limitations in the design and operation of CPT-ISOP-MCC systems are analyzed in detail. In order to comprehensively evaluate the CPT against the magnetically isolated concept, i.e. inductive power transfer (IPT) converter topology, a multi-objective optimization is performed with respect to the achievable efficiency and power density for both types of converters. Based on the optimization result, a prototype of a CPT GaN DC/DC converter is realized and compared to its IPT GaN DC/DC converter counterpart, along with measurement results. Furthermore, a complete single-phase 3.3kWAC/DC converter system with a high power density of ρ = 3.92kW/dm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">3</sup> and an efficiency of η = 97% is presented, incorporating the CPT-DC/DC converter stages in ISOP topology.
Des « durs à cuire » vaincus par la chimie douce (2013)

Le quartz, l’une des phases cristallines de la silice, second minéral le plus abondant au monde, était très difficile à purifier et à nanostructurer pour la microélectronique jusqu’à aujourd’hui. En effet, des chercheurs du Laboratoire de chimie de la matière condensée de Paris (CNRS / Collège de France / UPMC) en collaboration avec l'Institut des matériaux de Barcelone et l’Institut Laue-Langevin de Grenoble ont réussi un tour de force exceptionnel : obtenir avec un procédé simple un film de...
BAFF: B cell survival factor and emerging therapeutic target for autoimmune disorders (2003)

The prevailing treatment strategies for autoimmune disorders employ global immunosuppressants that have harmful side effects with long-term use. A new vision for drug development relies on the generation of therapeutics that have specific and narrow targets, such as pathogenic cell populations. The cellular processes that initiate and maintain B cell dysregulation are not well understood and autoimmune disease results, in part, from the survival and activation of self-reactive B cells. Such B cells produce tissue-damaging pathogenic autoantibodies. BAFF (B cell-activating factor belonging to the TNF family), a member of the TNF family of ligands, may play a role in B cell-mediated diseases. BAFF is a survival factor for peripheral B cells. When BAFF is overexpressed in mice, B cell number and immunoglobulin production is increased and an autoimmune-like phenotype is observed. Mouse models of lupus-nephritis have been shown to exhibit increased serum BAFF levels correlating with disease severity, and many autoimmune patients were found to have higher levels of circulating BAFF than healthy volunteers. Thus, modulating the level and activity of BAFF in these patients may alleviate symptoms associated with their disease. Several potential therapeutic inhibitors targeting BAFF are under investigation, including an anti-BAFF antibody and receptor-Fc fusion proteins.
Synergistic effects of methyl 2-cyano-3,11-dioxo-18beta-olean-1,-12-dien-30-oate and erlotinib on erlotinib-resistant non-small cell lung cancer cells (2021)

Non-small cell lung cancer (NSCLC) is often characterized by an underlying mutation in the epidermal growth factor receptor (EGFR), contributing to aggressive metastatic disease. Methyl 2-cyano-3,11-dioxo-18beta-olean-1,12-dien-30-oate (CDODA-Me), a glycyrrhetinic acid derivative, reportedly improves the therapeutic response to erlotinib (ERL), an EGFR tyrosine kinase inhibitor. In the present study, we performed a series of studies to demonstrate the efficacy of CDODA-Me (2 μM) in sensitizing HCC827R (ERL-resistant) cells to ERL. Herein, we first established the selectivity of ERL-induced drug resistance in the HCC827R cells, which was sensitized when ERL was combined with CDODA-Me (2 μM), shifting the IC<sub>50</sub> from 23.48 μM to 5.46 μM. Subsequently, whole transcriptomic microarray expression data demonstrated that the combination of ERL + CDODA-Me elicited 210 downregulated genes (0.44% of the whole transcriptome (WT)) and 174 upregulated genes (0.36% of the WT), of which approximately 80% were unique to the ERL + CDODA-Me group. Synergistic effects centered on losses to cell cycle progression transcripts, a reduction of minichromosome maintenance complex components (MCM2-7), all key components of the Cdc45·MCM2-7GINS (CMG) complex, and replicative helicases; these effects were tantamount to the upregulation of processes associated with the nuclear factor erythroid 2 like 2 translational response to oxidative stress, including sulfiredoxin 1, heme oxygenase 1, and stress-induced growth inhibitor 1. Collectively, these findings indicate that the synergistic therapeutic effects of ERL + CDODA-Me on resistant NSCLC cells are mediated via the inhibition of mitosis and induction of oxidative stress.
Railing Nanoparticles Along Activated Tracks Towards Continuous-Flow Electrokinetic Enrichment from Blood Plasma (2020)

We report on a unique microfluidic device that can enrich nanoparticles in a continuous flow by railing them along activated tracks (electrodes). This was achieved based on dielectrophoretic force and electrohydrodynamic drag (electrothermal rolls and AC electroosmosis) in both low and high conductive media. The results have implication for the isolation of high quality and pure nanoparticles such as exosomes from biofluids for applications in cancer diagnosis and prognosis.
Age-related differences in neural activities during risk taking as revealed by functional MRI (2007)

Previous research has clearly documented that risky decision making is different in young and older adults. Yet, there has been a relative dearth of research that seeks to understand such age-related changes in the neural activities associated with risk taking. To address this research issue, 21 men (12 young men, mean age 29.9 +/- 6.2 years and 9 older men, mean age 65.2 +/- 4.2 years) performed a risky-gains task while their brain activities were monitored by an fMRI scanner. The older adults, relative to their younger peers, presented with contralateral prefrontal activity, particularly at the orbitofrontal cortex. Furthermore, stronger activation of the right insula was observed for the older-aged participants compared to the younger-aged adults. The findings of this study are consistent with the a priori speculations established in accordance with the HAROLD model as well as previous findings. Findings of this study suggest that when making risky decisions, there may be possible neuropsychological mechanisms underlying the change in impulsive and risk-taking behaviors during the course of natural ageing.
ChemInform Abstract: 5‐Cyano‐1‐(3‐(N‐methylpyrrolidin‐2R‐ylmethyl)indol‐5‐yl)benzimidazole ( CP‐161,242): A Potent, Centrally Active 5‐HT1D Receptor Agonist and Benzodiazepine Partial Agonist. (1996)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Structures of potent selective peptide mimetics bound to carboxypeptidase B (2008)

This article reports the crystal structures of inhibitors of the functional form of thrombin-activatable fibrinolysis inhibitor (TAFIa). In vivo experiments indicate that selective inhibitors of TAFIa would be useful in the treatment of heart attacks. Since TAFIa rapidly degrades in solution, the homologous protein porcine pancreatic carboxypeptidase B (pp-CpB) was used in these crystallography studies. Both TAFIa and pp-CpB are zinc-based exopeptidases that are specific for basic residues. The final development candidate, BX 528, is a potent inhibitor of TAFIa (2 nM) and has almost no measurable effect on the major selectivity target, carboxypeptidase N. BX 528 was designed to mimic the tripeptide Phe-Val-Lys. A sulfonamide replaces the Phe-Val amide bond and a phosphinate connects the Val and Lys groups. The phosphinate also chelates the active-site zinc. The electrostatic interactions with the protein mimic those of the natural substrate. The primary amine in BX 528 forms a salt bridge to Asp255 at the base of the S1' pocket. The carboxylic acid interacts with Arg145 and the sulfonamide is hydrogen bonded to Arg71. Isopropyl and phenyl groups replace the side chains of Val and Phe, respectively. A series of structures are presented here that illustrate the evolution of BX 528 from thiol-based inhibitors that mimic a free C-terminal arginine. The first step in development was the replacement of the thiol with a phosphinate. This caused a precipitous drop in binding affinity. Potency was reclaimed by extending the inhibitors into the downstream binding sites for the natural substrate.