25,267 research outputs found
The investigational Cystic Fibrosis drug Trimethylangelicin directly modulates CFTR by stabilizing the first membrane-spanning domain.
No full textCystic Fibrosis (CF) is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator
(CFTR) gene. The most common mutation, deletion of phenylalanine 508 (F508del), disrupts tertiary
assembly, causing protein misprocessing and loss of CFTR function in epithelial tissues. Lumacaftor
(VX-809) is a Class 1 corrector molecule shown to partially rescue misprocessing of F508del and together
with the potentiator of channel activity: ivacaftor (VX-770) has been approved for treatment of CF
patients homozygous for the F508del mutation. The specificity of these modulators for CFTR is thought
to be conferred through direct binding. Trimethylangelicin (TMA) is a distinct small molecule modulator,
previously shown to exhibit both corrector and potentiator activities. We were prompted to determine if
TMA also mediates these activities by direct binding. Interestingly, we found that like VX-770, TMA was
effective in enhancing anion efflux mediated by purified WT-CFTR reconstituted in phospholipid liposomes.
Furthermore, like VX-809, TMA was effective in stabilizing the functional expression of CFTR lacking
the regulatory ‘‘R” domain or second nucleotide-binding domain (NBD2). The smallest domain that
was stabilized by TMA binding was the first membrane-spanning domain (MSD1) as previously observed
for VX-809. Together, our findings support the claim that TMA binds directly to CFTR, and despite its distinct
chemical structure, shares similar mechanisms as VX-770 and VX-809 to potentiate and stabilize
CFTR, respectively
Manifeste des bibliothèques des Écoles Supérieures d\u27Art et de design
No full textNous, bibliothécaires et documentalistes de BEAR, nous réunissons autour des valeurs suivantes :
• Les bibliothèques et centres de documentation sont des lieux de diffusion de l’art et de la culture et de médiation entre les ressources, les savoirs et les publics. Les bibliothèques et centres de documentation d’écoles d’art et de design assurent en ce
sens des missions de service public, reconnaissent la charte de l’ABF, le manifeste de l’IFLA et de l’UNESCO, et y ajoutent leurs spécificités.
• Au cœur des écoles, les bibliothèques et centres de documentation sont des lieux où se rencontrent tous leurs publics, ainsi que le public extérieur. Il s’agit de biens communs, en constante évolution, qui se bâtissent ensemble.
• Les bibliothèques et centres de documentation affirment leur dimension inclusive
CE Challenges: Work to Do
No full textCE has been used for more than two decades now. Despite many successes and advantages, there are still many challenges to be addressed. These challenges are both technical and organisational. In the paper we will address the current challenges of CE. Many challenges are related to the exchange of data and knowledge and to the systems that make data and knowledge exchange possible. Although much progress has been made in enabling extensive data and knowledge exchange and use, much remains to be wished. For example, there are still barriers to data exchange. Technically, these barriers may consist of different formats, differences in infrastructures and systems, and different semantics. There are also organisational and political barriers. For example, investment in information system may heavily impact upstream suppliers, while revenues of better information exchange may predominantly be gained by downstream actors. Without sharing costs and revenues, chain-wide information exchange will not be easily realised. Another barrier is the possible lack of willingness to share information, because of potential misuse of knowledge and loss of power. The paper is organised as follows. First we will describe the current manifestation of CE as described in a recent book. Second, we will list current trends in CE. Third, we will present some Critical Success Factors (CSFs) that are considered relevant for implementing and adapting CE practices. Last, we indicate some research and practical questions to be addressed, especially for areas that have a high potential and actual impact. </p
Synthesis optimization and charge carrier transfer mechanism in LiLuSiO<sub>4</sub>:Ce, Tm storage phosphor
No full textLiLuSiO4:Ce and LiLuSiO4:Ce, Tm show very efficient charge carrier storage properties upon beta irradiation after samples have received treatment in vacuum. They outperform the commercial storage phosphor BaFBr(I):Eu2+ in many aspects. The influence of the synthesis conditions, Ce and Tm concentration, nonstoichiometry and codoping with Ca, Hf, Al and Ge are reported. Based on the results of the synthesis optimization, thermoluminescence (TL) emission and TL excitation spectra a mechanism of charge carrier transfer, storage, and recombination during irradiation and thermal or optical readout is proposed.Accepted Author ManuscriptRST/Fundamental Aspects of Materials and EnergyRST/Luminescence Material
The impact of P(NDI2OD-T2) crystalline domains on the open-circuit voltage of bilayer all-polymer solar cells with an inverted configuration
No full textWe fabricated P(NDI2OD-T2)/PTB7 bilayer all-polymer solar cells with an inverted configuration, where the annealing temperature was systematically varied. The current density-voltage behavior was investigated and the structural properties of the P(NDI2OD-T2) layers were characterized. Absorption spectroscopy, surface morphology, and crystallite analysis showed that increasing phase segregation of P(NDI2OD-T2) films occurred as the annealing temperature increased. We found that, as the P(NDI2OD-T2) stacking improved, with larger domains, the open-circuit voltage decreased and the saturation dark current density increased. This work provides a guide for the processing of P(NDI2OD-T2) layers to maximize the power conversion efficiency of all-polymer solar cells. (C) 2015 Author(s).open1186sciescopu
Data and code for: Variational Graph Author Topic Modeling
No full textThis is the tensorflow implementation of KDD-2022 paper "Variational Graph Author Topic Modeling" by Delvin Ce Zhang and Hady W. Lauw.
VGATM is a Graph Neural Network model that extracts interpretable topics for documents with authors and venues. Topics of documents then fulfill document classification, citation prediction, etc.
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Updated analytical solutions of continuity equation for electron beams precipitation – I. Pure collisional and pure ohmic energy losses
No full textWe present updated analytical solutions of continuity equations for power-law beam electrons precipitating in (a) purely collisional losses and (b) purely ohmic losses. The solutions of continuity equation (CE) normalized on electron density presented in Dobranskis & Zharkova are found by method of characteristics eliminating a mistake in the density characteristic pointed out by Emslie et al. The corrected electron beam differential densities (DD) for collisions are shown to have energy spectra with the index of −(γ + 1)/2, coinciding with the one derived from the inverse problem solution by Brown, while being lower by 1/2 than the index of −γ/2 obtained from CE for electron flux. This leads to a decrease of the index of mean electron spectra from −(γ − 2.5) (CE for flux) to −(γ − 2.0) (CE for electron density). The similar method is applied to CE for electrons precipitating in electric field induced by the beam itself. For the first time, the electron energy spectra are calculated for both constant and variable electric fields by using CE for electron density. We derive electron DD for precipitating electrons (moving towards the photosphere, μ = +1) and ‘returning’ electrons (moving towards the corona, μ = −1). The indices of DD energy spectra are reduced from −γ − 1 (CE for flux) to −γ (CE for electron density). While the index of mean electron spectra is increased by 0.5, from −γ + 0.5 (CE for flux) to −γ + 1(CE for electron density). Hard X-ray intensities are also calculated for relativistic cross-section for the updated differential spectra revealing closer resemblance to numerical Fokker–Planck (FP) solutions
Introduction and Author Biographical Notes
No full textThe Introductory Notes include The Cutting EDge\u27s mission statement, editorial board, founder\u27s note, and author\u27s biographies
From the Editors and Author Biographical Notes
No full textLetter from the Editors and Author Biographical Note
Surface modification with MK-2 organic dye in a ZnO/P3HT hybrid solar cell: Impact on device performance
No full textThe photovoltaic performance of a hybrid ZnO/P3HT heterojunction was improved by modifying the device surface with the MK-2 dye. This organic dye enhanced the compatibility between the polymer and the metal oxide, increased the exciton separation efficiency, and improved the molecular ordering in the charge transport network. The resulting device displayed a substantial enhancement in the photocurrent, open circuit voltage, and fill factor, leading to a 12-fold increase in the power conversion efficiency relative to the unmodified device, from 0.13% to 1.53%. (C) 2014 Author(s).open1145sciescopu
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