87 research outputs found
Radiatively inefficient MHD accretion-ejection structures
We present magnetohydrodynamic simulations of a resistive accretion disk
continuously launching transmagnetosonic, collimated jets. We time-evolve the
full set of magnetohydrodynamic equations, but neglect radiative losses in the
energetics (radiatively inefficient). Our calculations demonstrate that a jet
is self-consistently produced by the interaction of an accretion disk with an
open, initially bent large-scale magnetic field. A constant fraction of heated
disk material is launched in the inner equipartition disk regions, leading to
the formation of a hot corona and a bright collimated, super-fastmagnetosonic
jet. We illustrate the complete dynamics of the ``hot'' near steady-state
outflow (where thermal pressure magnetic pressure) by showing force
balance, energy budget and current circuits. The evolution to this near
stationary state is analyzed in terms of the temporal variation of energy
fluxes controlling the energetics of the accretion disk. We find that unlike
advection-dominated accretion flow, the energy released by accretion is mainly
sent into the jet rather than transformed into disk enthalpy. These magnetized,
radiatively inefficient accretion-ejection structures can account for
under-luminous thin disks supporting bright fast collimated jets as seen in
many systems displaying jets (for instance M87).Comment: Astrophysical Journal (in press). Figures are missing due to file
size restrictions. To have the complete paper just click on
http://www-laog.obs.ujf-grenoble.fr/~fcasse/MS56638.pd
Influência do armazenamento de substratos orgânicos no desenvolvimento de mudas de alface.
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Novel computational methods for increasing PCR primer design effectiveness in directed sequencing
<p>Abstract</p> <p>Background</p> <p>Polymerase chain reaction (PCR) is used in directed sequencing for the discovery of novel polymorphisms. As the first step in PCR directed sequencing, effective PCR primer design is crucial for obtaining high-quality sequence data for target regions. Since current computational primer design tools are not fully tuned with stable underlying laboratory protocols, researchers may still be forced to iteratively optimize protocols for failed amplifications after the primers have been ordered. Furthermore, potentially identifiable factors which contribute to PCR failures have yet to be elucidated. This inefficient approach to primer design is further intensified in a high-throughput laboratory, where hundreds of genes may be targeted in one experiment.</p> <p>Results</p> <p>We have developed a fully integrated computational PCR primer design pipeline that plays a key role in our high-throughput directed sequencing pipeline. Investigators may specify target regions defined through a rich set of descriptors, such as Ensembl accessions and arbitrary genomic coordinates. Primer pairs are then selected computationally to produce a minimal amplicon set capable of tiling across the specified target regions. As part of the tiling process, primer pairs are computationally screened to meet the criteria for success with one of two PCR amplification protocols. In the process of improving our sequencing success rate, which currently exceeds 95% for exons, we have discovered novel and accurate computational methods capable of identifying primers that may lead to PCR failures. We reveal the laboratory protocols and their associated, empirically determined computational parameters, as well as describe the novel computational methods which may benefit others in future primer design research.</p> <p>Conclusion</p> <p>The high-throughput PCR primer design pipeline has been very successful in providing the basis for high-quality directed sequencing results and for minimizing costs associated with labor and reprocessing. The modular architecture of the primer design software has made it possible to readily integrate additional primer critique tests based on iterative feedback from the laboratory. As a result, the primer design software, coupled with the laboratory protocols, serves as a powerful tool for low and high-throughput primer design to enable successful directed sequencing.</p
The PHENIX Experiment at RHIC
The physics emphases of the PHENIX collaboration and the design and current
status of the PHENIX detector are discussed. The plan of the collaboration for
making the most effective use of the available luminosity in the first years of
RHIC operation is also presented.Comment: 5 pages, 1 figure. Further details of the PHENIX physics program
available at http://www.rhic.bnl.gov/phenix
The effect of LRRK2 loss-of-function variants in humans
Analysis of large genomic datasets, including gnomAD, reveals that partial LRRK2 loss of function is not strongly associated with diseases, serving as an example of how human genetics can be leveraged for target validation in drug discovery. Human genetic variants predicted to cause loss-of-function of protein-coding genes (pLoF variants) provide natural in vivo models of human gene inactivation and can be valuable indicators of gene function and the potential toxicity of therapeutic inhibitors targeting these genes(1,2). Gain-of-kinase-function variants in LRRK2 are known to significantly increase the risk of Parkinson's disease(3,4), suggesting that inhibition of LRRK2 kinase activity is a promising therapeutic strategy. While preclinical studies in model organisms have raised some on-target toxicity concerns(5-8), the biological consequences of LRRK2 inhibition have not been well characterized in humans. Here, we systematically analyze pLoF variants in LRRK2 observed across 141,456 individuals sequenced in the Genome Aggregation Database (gnomAD)(9), 49,960 exome-sequenced individuals from the UK Biobank and over 4 million participants in the 23andMe genotyped dataset. After stringent variant curation, we identify 1,455 individuals with high-confidence pLoF variants in LRRK2. Experimental validation of three variants, combined with previous work(10), confirmed reduced protein levels in 82.5% of our cohort. We show that heterozygous pLoF variants in LRRK2 reduce LRRK2 protein levels but that these are not strongly associated with any specific phenotype or disease state. Our results demonstrate the value of large-scale genomic databases and phenotyping of human loss-of-function carriers for target validation in drug discovery.Peer reviewe
Genome sequence of the necrotrophic plant pathogen Pythium ultimum reveals original pathogenicity mechanisms and effector repertoire
Background: Pythium ultimum (P. ultimum) is a ubiquitous oomycete plant pathogen responsible for a variety of diseases on a broad range of crop and ornamental species. Results: The P. ultimum genome (42.8 Mb) encodes 15,290 genes and has extensive sequence similarity and synteny with related Phytophthora species, including the potato blight pathogen Phytophthora infestans. Whole transcriptome sequencing revealed expression of 86% of genes, with detectable differential expression of suites of genes under abiotic stress and in the presence of a host. The predicted proteome includes a large repertoire of proteins involved in plant pathogen interactions although surprisingly, the P. ultimum genome does not encode any classical RXLR effectors and relatively few Crinkler genes in comparison to related phytopathogenic oomycetes. A lower number of enzymes involved in carbohydrate metabolism were present compared to Phytophthora species, with the notable absence of cutinases, suggesting a significant difference in virulence mechanisms between P. ultimum and more host specific oomycete species. Although we observed a high degree of orthology with Phytophthora genomes, there were novel features of the P. ultimum proteome including an expansion of genes involved in proteolysis and genes unique to Pythium. We identified a small gene family of cadherins, proteins involved in cell adhesion, the first report in a genome outside the metazoans. Conclusions: Access to the P. ultimum genome has revealed not only core pathogenic mechanisms within the oomycetes but also lineage specific genes associated with the alternative virulence and lifestyles found within the pythiaceous lineages compared to the Peronosporaceae
Flexural behavior of general laminated composite and sandwich plates using a secant function based shear deformation theory
Author Correction: The mutational constraint spectrum quantified from variation in 141,456 humans
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