4,430 research outputs found
Stratospheric pollutant transports by planetary waves and tropical circulations
Radiosonde and U-2 aircraft data from the Intertropical Convergence Zone experiment of July, 1977 were analyzed. The radiosonde data above 15 km was plotted in the form of time-height sections so that wave motions in the meteorological variables (temperature, zonal wind, and meridional wind) could be easily delineated. The results showed the presence of a planetary 16 day Kelvin wave. More significantly, large amplitude gravity waves with vertical wavelengths on the order of 3-6 km were found. Spectral analysis of frequencies showed peaks in meridional wind variance at 2-3 days and 5 days, with the shorter periods stronger at higher altitudes. In the time domain, two instances of organized wave groups propagating upward into the stratosphere were isolated. Associated with one of these wave groups was a region of very large vertical shear in which either turbulence or small scale (10 km wavelength or less) gravity wave activity had been found by the U-2 aircraft
Therapeutic Silencing of Mutant \u3cem\u3eHuntingtin\u3c/em\u3e by Targeting Single Nucleotide Polymorphisms: A Dissertation
Huntington’s disease (HD) is an autosomal dominant, progressive neurodegenerative disorder. Invariably fatal, HD is caused by expansion of the CAG repeat region in exon 1 of the Huntingtin gene which creates a toxic protein with an extended polyglutamine tract 1. Silencing mutant Huntingtin messenger RNA (mRNA) is a promising therapeutic approach 2-6. The ideal silencing strategy would reduce mutant Huntingtin while leaving the wild-type mRNA intact. Unfortunately, targeting the disease causing CAG repeat expansion is difficult and risks targeting other CAG repeat containing genes.
We examined an alternative strategy, targeting single nucleotide polymorphisms (SNPs) in the Huntingtin mRNA. The feasibility of this approach hinges on the presence of a few common highly heterozygous SNPs which are amenable to SNP-specific targeting. In a population of HD patients from Europe and the United states, forty-eight percent were heterozygous at a single SNP site; one isoform of this SNP is associated with HD. Seventy-five percent of patients are heterozygous at least one of three frequently heterozygous SNPs. Consequently, only five allele-specific siRNAs are required to treat three-quarters of the patients in the European and U.S. patient populations. We have designed and validated siRNAs targeting these SNPs.
We also developed artificial microRNAs (miRNAs) targeting Huntingtin SNPs for delivery using recombinant adeno-associated viruses (rAAVs). Both U6 promoter driven and CMV promoter driven miRNAs can discriminate between matched and mismatched targets in cell culture but the U6 promoter driven miRNAs produce the mature miRNA at levels exceeding those of the vast majority of endogenous miRNAs. The U6 promoter driven miRNAs can produce a number of unwanted processing products, most likely due to a combination of overexpression and unintended export of the pri-miRNA from the nucleus. In contrast, CMV-promoter driven miRNAs produce predominantly a single species at levels comparable to endogenous miRNAs. Injection of recombinant self complementary AAV9 viruses carrying polymerase II driven Huntingtin SNP targeting miRNAs into the striatum results in expression of the mature miRNA sequence in the brain and has no significant effect on endogenous miRNAs. Matched, but not mismatched SNP-targeting miRNAs reduce inclusions in a knock-in mouse model of HD. These studies bring us closer to an allele-specific therapy for Huntington’s disease
The metaphysics of Machian frame-dragging
The paper investigates the kind of dependence relation that best portrays Machian frame-dragging in general relativity. The question is tricky because frame-dragging relates local inertial frames to distant distributions of matter in a time-independent way, thus establishing some sort of non-local link between the two. For this reason, a plain causal interpretation of frame-dragging faces huge challenges. The paper will shed light on the issue by using a generalized structural equation model analysis in terms of manipulationist counterfactuals recently applied in the context of metaphysical enquiry by Schaffer (2016) and Wilson (2017). The verdict of the analysis will be that frame-dragging is best understood in terms of a novel type of dependence relation that is half-way between causation and grounding
Hydrological connectivity inferred from diatom transport through the riparian-stream system
Funding for this research was provided by the Luxembourg National Research Fund (FNR) in the framework of the BIGSTREAM (C09/SR/14), ECSTREAM (C12/SR/40/8854) and CAOS (INTER/DFG/11/01) projects. We are most grateful to the Administration des Services Techniques de l’Agriculture (ASTA) for providing meteorological data. We also acknowledge Delphine Collard for technical assistance in diatom sample treatment and preparation, François Barnich for the water chemistry analyses, and Jean-François Iffly, Christophe Hissler, Jérôme Juilleret, Laurent Gourdol and Julian Klaus for their constructive comments on the project and technical assistance in the field.Peer reviewedPublisher PD
Temporal simulations and stability analyses of elastic splitter plates interacting with cylinder wake flow
Instabilities developing in a configuration constituted by an elastic plate clamped behind a rigid cylinder are analysed in this paper. The interaction between the wake flow generated by the cylinder with the elastic plate leads to self-developing vortex-induced vibrations. Depending of the stiffness of the elastic plate, the plate may oscillate about a non-deviated or a deviated mean transverse position. After having presented non-linear results computed with time-marching simulations, the instabilities are analysed in terms of a fully coupled fluid-structure eigenvalue analysis. We show that the linear stability analysis is able to predict the unstable regions, and provide a good prediction of the unstable vibration frequencies. The mean deviation is characterized by a steady divergence mode in the eigenvalue spectrum, while unstable, unsteady vortex-induced vibration modes show lock-in phenomena
Lebowitz Inequalities for Ashkin-Teller Systems
We consider the Ashkin-Teller model with negative four-spin coupling but
still in the region where the ground state is ferromagnetic. We establish the
standard Lebowitz inequality as well as the extension that is necessary to
prove a divergent susceptibility.Comment: Ams-TeX, 12 pages; two references added, final version accepted for
publication in Physica
Airborne Tropical TRopopause EXperiment (ATTREX) 2014 Western Pacific Campaign
The NASA Airborne Tropical TRopopause EXperiment (ATTREX) is a series of airborne campaigns focused on understanding physical processes in the Tropical Tropopause Layer (TTL) and their role in atmospheric chemistry and climate. ATTREX is using the high-altitude, long-duration NASA Global Hawk Unmanned Air System to make in situ and remote-sensing measurements spanning the Pacific. A particular ATTREX emphasis is to better understand the dehydration of air as it passes through the cold tropical tropopause region. The ATTREX payload contains 12 in situ and remote sensing instruments that measure water vapor, carbon dioxide, methane, nonmethane hydrocarbons, sulfur hexafluoride, chlorofluorocarbons, nitrous oxide), reactive chemical compounds (ozone, bromine, nitrous oxide), meteorological parameters, and radiative fluxes. During January-March, 2014, the Global Hawk was deployed to Guam for ATTREX flights. Six science flights were conducted from Guam (in addition to the transits across the Pacific), resulting in over 100 hours of Western Pacific TTL sampling and about 180 vertical profiles through the TTL. I will provide an overview of the dataset, with examples of the measurements including meteorological parameters, clouds and water vapor, and chemical tracers
Assessing winter storm flow generation by means of permeability of the lithology and hydrological soil processes
International audienceIn this study two approaches are used to predict winter storm flow coefficients in meso-scale basins (10 km2 to 1000 km2) with a view to regionalization. The winter storm flow coefficient corresponds to the ratio between rainfall and direct discharge caused by this rainfall. It is basin specific and supposed to give an integrated response to rainfall. The two approaches, which used the permeability of the substratum and soil hydrological processes as basin attributes are compared. The study area is the Rhineland Palatinate and the Grand Duchy of Luxembourg and the study focuses on the Nahe basin and its 16 sub-basins (Rhineland Palatinate). For the comparison, three statistical models were derived by means of regression analysis. The models used the winter storm flow coefficient as the dependent variable in the models; the independent variables were the permeability of the substratum, preliminary derived hydrological soil processes and a combination of both. It is assumed that the permeability and the preliminary derived hydrological soil processes carry different layers of information. Cross-validation and a statistical test were used to determine and evaluate model differences. The cross-validation resulted in a best model performance for the model that used both parameters, followed by the model that used the preliminary hydrological soil processes. From the statistical test it was concluded that the models come from different populations, carrying different information layers. Analysis of the residuals of the models indicated that the permeability and hydrological soil processes did provide complementary information. Simple linear models appeared to perform well in describing the winter storm flow coefficient at the meso-scale when a combination of the permeability of the substratum and soil hydrological processes served as independent parameters
Assessing winter storm flow generation by means of permeability of the lithology and dominating runoff production processes
International audienceIn this study two approaches are used to predict winter storm flow coefficients in meso-scale basins (10 km² to 1000 km²) with a view to regionalization. The winter storm flow coefficient corresponds to the ratio between direct discharge and rainfall. It is basin specific and supposed to give an integrated response to rainfall. The two approaches, which used the permeability of the substratum and dominating runoff generation processes as basin attributes are compared. The study area is the Rhineland Palatinate and the Grand Duchy of Luxembourg and the study focuses on the Nahe basin and its 16 sub-basins (Rhineland Palatinate). For the comparison, three statistical models were derived by means of regression analysis. The models used the winter storm flow coefficient as the dependent variable; the independent variables were the permeability of the substratum, preliminary derived dominating runoff generation processes and a combination of both. It is demonstrated that the permeability and the preliminary derived processes carry different layers of information. Cross-validation and statistical tests were used to determine and evaluate model differences. The cross-validation resulted in a best model performance for the model that used both parameters, followed by the model that used the dominant runoff generation processes. From the statistical tests it was concluded that the models come from different populations, carrying different information layers. Analysis of the residuals of the models indicated that the permeability and runoff generation processes did provide complementary information. Simple linear models appeared to perform well in describing the winter storm flow coefficient at the meso-scale when a combination of the permeability of the substratum and dominating runoff generation processes served as independent parameters
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