16,177 research outputs found
Innovative in silico approaches to address avian flu using grid technology
The recent years have seen the emergence of diseases which have spread very
quickly all around the world either through human travels like SARS or animal
migration like avian flu. Among the biggest challenges raised by infectious
emerging diseases, one is related to the constant mutation of the viruses which
turns them into continuously moving targets for drug and vaccine discovery.
Another challenge is related to the early detection and surveillance of the
diseases as new cases can appear just anywhere due to the globalization of
exchanges and the circulation of people and animals around the earth, as
recently demonstrated by the avian flu epidemics. For 3 years now, a
collaboration of teams in Europe and Asia has been exploring some innovative in
silico approaches to better tackle avian flu taking advantage of the very large
computing resources available on international grid infrastructures. Grids were
used to study the impact of mutations on the effectiveness of existing drugs
against H5N1 and to find potentially new leads active on mutated strains. Grids
allow also the integration of distributed data in a completely secured way. The
paper presents how we are currently exploring how to integrate the existing
data sources towards a global surveillance network for molecular epidemiology.Comment: 7 pages, submitted to Infectious Disorders - Drug Target
Functional rescue of dystrophin deficiency in mice caused by frameshift mutations using Campylobacter jejuni Cas9
Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscle wasting disease caused by mutations in the DMD gene. In 51% of DMD cases, a reading frame is disrupted because of deletion of several exons. Here, we show that CjCas9 derived from Campylobacter jejuni can be
used as a gene editing tool to correct an out-of-frame Dmd exon in Dmd knockout mice. Herein, we used Cas9 derived from S. pyogenes to generate Dmd knockout (KO) mice with a frameshift mutation in Dmd gene. Then, we expressed CjCas9, its single-guide RNA, and the eGFP gene
in the tibialis anterior muscle of the Dmd KO mice using an all-in-one adeno-associated virus (AAV) vector. CjCas9 cleaved the target site in the Dmd gene efficiently in vivo and induced small insertions or deletions at the target site. This treatment resulted in conversion of the
disrupted Dmd reading frame from out-of-frame to in-frame, leading to the expression of dystrophin in the sarcolemma. Importantly, muscle strength was enhanced in the CjCas9-treated muscles, without off-target mutations, indicating high efficiency and specificity of CjCas9. This work suggests that in vivo DMD frame correction, mediated by CjCas9 has great potential for the treatment of DMD and other neuromuscular diseases
Bound-to-bound and bound-to-continuum optical transitions in combined quantum dot - superlattice systems
By combining band gap engineering with the self-organized growth of quantum
dots, we present a scheme of adjusting the mid-infrared absorption properties
to desired energy transitions in quantum dot based photodetectors. Embedding
the self organized InAs quantum dots into an AlAs/GaAs superlattice enables us
to tune the optical transition energy by changing the superlattice period as
well as by changing the growth conditions of the dots. Using a one band
envelope function framework we are able, in a fully three dimensional
calculation, to predict the photocurrent spectra of these devices as well as
their polarization properties. The calculations further predict a strong impact
of the dots on the superlattices minibands. The impact of vertical dot
alignment or misalignment on the absorption properties of this dot/superlattice
structure is investigated. The observed photocurrent spectra of vertically
coupled quantum dot stacks show very good agreement with the calculations.In
these experiments, vertically coupled quantum dot stacks show the best
performance in the desired photodetector application.Comment: 8 pages, 10 figures, submitted to PR
Physical routes for the synthesis of kesterite
This paper provides an overview of the physical vapor technologies used to synthesize Cu2ZnSn(S,Se)4
thin films as absorber layers for photovoltaic applications. Through the years, CZT(S,Se) thin films
have been fabricated using sequential stacking or co-sputtering of precursors as well as using
sequential or co-evaporation of elemental sources, leading to high-efficient solar cells. In addition,
pulsed laser deposition of composite targets and monograin growth by the molten salt method were
developed as alternative methods for kesterite layers deposition. This review presents the growing
increase of the kesterite-based solar cell efficiencies achieved over the recent years. A historical
description of the main issues limiting this efficiency and of the experimental pathways designed to
prevent or limit these issues is provided and discussed as well. Afinal section is dedicated to the
description of promising process steps aiming at further improvements of solar cell efficiency, such as
alkali doping and bandgap grading1. R Caballero and M León acknowledge financial support via the Spanish Ministry of Science, Innovation and Universities project (WINCOST, ENE2016-80788-C5-2-R) and thank H2020 EU Programme under the project INFINITE-CELL (H2020-MSCA-RISE-2017-777968).
2. S Canulescu and J Schou acknowledge the support from Innovation Fund Denmark.
3. D-H Kim acknowledges financial support via the DGIST R&D Program of the Ministry of Science and ICT, KOREA (18-BD-05).
4.C. Malerba acknowledges the support from the Italian Ministry of Economic development in the framework of the Operating Agreement with ENEA for the Research on the Electric System.
5.A Redinger acknowledges financial support via the FNR Attract program, Project : SUNSPOT, Nr.11244141.
6. E Saucedo thanks H2020 EU Programme under the projects STARCELL (H2020-NMBP-03-2016-720907) and INFINITE-CELL (H2020-MSCA-RISE-2017-777968), the Spanish Ministry of Science, Innovation and Universities for the IGNITE project (ENE2017-87671-C3-1-R), and the European Regional Development Funds (ERDF, FEDER Programa Competitivitat de Catalunya 2007–2013). IREC belong to
the SEMS (Solar Energy Materials and Systems) Consolidated Research Group of the ‘Generalitat de Catalunya’ (Ref. 2017 SGR 862).
7. Taltech acknowledges financial support via the Estonian Ministry of Education and Research funding project IUT19-28 and the European Union Regional Development Fund, Project TK141.
8. B Vermang has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (Grant Agreement No 715027
Functional Rescue of Dystrophin Deficiency in Mice Caused by Frameshift Mutations Using Campylobacter jejuni Cas9
Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscle-wasting disease caused by mutations in the DMD gene. In 51% of DMD cases, a reading frame is disrupted because of deletion of several exons. Here, we show that CjCas9 derived from Campylobacter jejuni can be used as a gene-editing tool to correct an out-of-frame Dmd exon in Dmd knockout mice. Herein, we used Cas9 derived from S. pyogenes to generate Dmd knockout mice with a frameshift mutation in Dmd gene. Then, we expressed CjCas9, its single-guide RNA, and the EGFP gene in the tibialis anterior muscle of the Dmd knockout mice using an all-in-one adeno-associated virus (AAV) vector. CjCas9 cleaved the target site in the Dmd gene efficiently in vivo and induced small insertions or deletions at the target site. This treatment resulted in conversion of the disrupted Dmd reading frame from out of frame to in frame, leading to the expression of dystrophin in the sarcolemma. Importantly, muscle strength was enhanced in the CjCas9-treated muscles, without off-target mutations, indicating high efficiency and specificity of CjCas9. This work suggests that in vivo DMD frame correction, mediated by CjCas9, has great potential for the treatment of DMD and other neuromuscular diseases. Koo et al. demonstrate that CjCas9 derived from Campylobacter jejuni can be used as a gene-editing tool to correct an out-of-frame Dmd exon in Dmd knockout mice. This study provides the therapeutic utility of CjCas9 for the treatment of Duchenne muscular dystrophy and other neuromuscular diseases
Gastrodia Elata Bl Attenuates Methamphetamine-Induced Dopaminergic Toxicity Via Inhibiting Oxidative Burdens
It has been recognized that Gastrodia elata Bl (GE), an oriental herb medicine, ameliorates various neurological disorders, that GE modulates the monoaminergic and GABAergic systems, and that GE possess antioxidant activities. We examined whether GE affects methamphetamine (MA)-induced striatal dopaminergic toxicity in mice. Treatment with MA (7.5 mg/kg, i.p. × 4) resulted in significant decreases in behavioural activity (as shown by locomotor activity and rota rod performance), dopamine level, tyrosine hydroxylase (TH) activity, and TH protein expression (as evaluated by immunocytochemistry and western blot analysis). In addition, MA treatment showed significant increases in lipid peroxidation [as evaluated by 4-hydroxy-2-nonenal (4-HNE) expression and malondialdehyde formation], protein oxidation (as shown by protein carbonyl expression and its formation), and reactive oxygen species (ROS) formation. Treatment with GE significantly attenuates MA-induced behavioural and dopaminergic impairments, and oxidative stresses in a dose-dependent manner. Our results suggest that GE treatment shows anti-dopaminergic effects in response to MA insult via, at least in part, inhibiting oxidative stresses in the striatum of the mice
Algebraic Fermi liquid from phase fluctuations: "topological" fermions, vortex "berryons" and QED3 theory of cuprate superconductors
Within the phase fluctuation model for the pseudogap state of cuprate
superconductors we identify a novel statistical "Berry phase" interaction
between the nodal quasiparticles and fluctuating vortices. The effective action
describing this model assumes the form of an anisotropic Euclidean quantum
electrodynamics in (2+1) dimensions (QED_3) and naturally generates the
marginal Fermi liquid behavior for its fermionic excitations. The doping axis
in the x-T phase diagram emerges as a quantum critical line which regulates low
energy fermiology. We examine the merits of our theory in light of available
experiments.Comment: 5 pages REVTeX + 2 PostScript Figures. Final version to appear in PR
An RxLR effector from phytophthora infestans prevents re-localisation of two plant NAC transcription factors from the endoplasmic reticulum to the nucleus
The plant immune system is activated following the perception of exposed, essential and invariant microbial molecules that are recognised as non-self. A major component of plant immunity is the transcriptional induction of genes involved in a wide array of defence responses. In turn, adapted pathogens deliver effector proteins that act either inside or outside plant cells to manipulate host processes, often through their direct action on plant protein targets. To date, few effectors have been shown to directly manipulate transcriptional regulators of plant defence. Moreover, little is known generally about the modes of action of effectors from filamentous (fungal and oomycete) plant pathogens. We describe an effector, called Pi03192, from the late blight pathogen Phytophthora infestans, which interacts with a pair of host transcription factors at the endoplasmic reticulum (ER) inside plant cells. We show that these transcription factors are released from the ER to enter the nucleus, following pathogen perception, and are important in restricting disease. Pi03192 prevents the plant transcription factors from accumulating in the host nucleus, revealing a novel means of enhancing host susceptibility
QED3 theory of pairing pseudogap in cuprates: From d-wave superconductor to antiferromagnet via "algebraic" Fermi liquid
High- cuprates differ from conventional superconductors in three crucial
aspects: the superconducting state descends from a strongly correlated
Mott-Hubbard insulator, the order parameter exhibits d-wave symmetry and
superconducting fluctuations play an all important role. We formulate a theory
of the pseudogap state in the cuprates by taking the advantage of these unusual
features. The effective low energy theory within the pseudogap phase is shown
to be equivalent to the (anisotropic) quantum electrodynamics in (2+1)
space-time dimensions (QED). The role of Dirac fermions is played by the
nodal BdG quasiparticles while the massless gauge field arises through
unbinding of quantum vortex-antivortex degrees of freedom. A detailed
derivation of this QED theory is given and some of its main physical
consequences are inferred for the pseudogap state. We focus on the properties
of symmetric QED and propose that inside the pairing protectorate it
assumes the role reminiscent of that played by the Fermi liquid theory in
conventional metals.Comment: 31 pages, 4 figures; replaced with revised versio
The role of biases in on-line learning of two-layer networks
The influence of biases on the learning dynamics of a two-layer neural network, a normalized soft-committee machine, is studied for on-line gradient descent learning. Within a statistical mechanics framework, numerical studies show that the inclusion of adjustable biases dramatically alters the learning dynamics found previously. The symmetric phase which has often been predominant in the original model all but disappears for a non-degenerate bias task. The extended model furthermore exhibits a much richer dynamical behavior, e.g. attractive suboptimal symmetric phases even for realizable cases and noiseless data
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