In the past ten years much work has been undertaken on developing mixture theory continuum models to describe kinetic sieving-driven size segregation. We propose an extension to these models that ...allows their application to bidisperse flows over inclined channels, with particles varying in density and size. Our model incorporates both a recently proposed explicit formula for how the total pressure is distributed among different species of particles, which is one of the key elements of mixture theory-based kinetic sieving models, and a shear rate-dependent drag. The resulting model is used to predict the range of particle sizes and densities for which the mixture segregates. The prediction of no segregation in the model is benchmarked by using discrete particle simulations, and good agreement is found when a single fitting parameter is used which determines whether the pressure scales with the diameter, surface area or volume of the particle.
Myotonic dystrophy Thornton, Charles A
Neurologic clinics,
08/2014, Letnik:
32, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Myotonic dystrophy (dystrophia myotonica, DM) is one of the most common lethal monogenic disorders in populations of European descent. DM type 1 was first described over a century ago. More recently, ...a second form of the disease, DM type 2 was recognized, which results from repeat expansion in a different gene. Both disorders have autosomal dominant inheritance and multisystem features, including myotonic myopathy, cataract, and cardiac conduction disease. This article reviews the clinical presentation and pathophysiology of DM and discusses current management and future potential for developing targeted therapies.
We present a comprehensive simulation of tropospheric chlorine
within the GEOS-Chem global 3-D model of oxidant–aerosol–halogen atmospheric
chemistry. The simulation includes explicit accounting of ...chloride
mobilization from sea salt aerosol by acid displacement of HCl and by other
heterogeneous processes. Additional small sources of tropospheric chlorine
(combustion, organochlorines, transport from stratosphere) are also included.
Reactive gas-phase chlorine Cl*, including Cl, ClO, Cl2, BrCl, ICl,
HOCl, ClNO3, ClNO2, and minor species, is produced by the
HCl+OH reaction and by heterogeneous conversion of sea salt aerosol
chloride to BrCl, ClNO2, Cl2, and ICl. The model
successfully simulates the observed mixing ratios of HCl in marine air
(highest at northern midlatitudes) and the associated HNO3
decrease from acid displacement. It captures the high ClNO2 mixing
ratios observed in continental surface air at night and attributes the
chlorine to HCl volatilized from sea salt aerosol and transported inland
following uptake by fine aerosol. The model successfully simulates the
vertical profiles of HCl measured from aircraft, where enhancements in the
continental boundary layer can again be largely explained by transport inland
of the marine source. It does not reproduce the boundary layer Cl2
mixing ratios measured in the WINTER aircraft campaign (1–5 ppt in the
daytime, low at night); the model is too high at night, which could be due to
uncertainty in the rate of the ClNO2+Cl- reaction, but we have
no explanation for the high observed Cl2 in daytime. The global
mean tropospheric concentration of Cl atoms in the model is 620 cm−3
and contributes 1.0 % of the global oxidation of methane, 20 % of
ethane, 14 % of propane, and 4 % of methanol. Chlorine chemistry
increases global mean tropospheric BrO by 85 %, mainly through the
HOBr+Cl- reaction, and decreases global burdens of tropospheric
ozone by 7 % and OH by 3 % through the associated bromine radical
chemistry. ClNO2 chemistry drives increases in ozone of up to
8 ppb over polluted continents in winter.
Highly oxygenated organic molecules (HOM) are formed in the atmosphere via autoxidation involving peroxy radicals arising from volatile organic compounds (VOC). HOM condense on pre-existing particles ...and can be involved in new particle formation. HOM thus contribute to the formation of secondary organic aerosol (SOA), a significant and ubiquitous component of atmospheric aerosol known to affect the Earth’s radiation balance. HOM were discovered only very recently, but the interest in these compounds has grown rapidly. In this Review, we define HOM and describe the currently available techniques for their identification/quantification, followed by a summary of the current knowledge on their formation mechanisms and physicochemical properties. A main aim is to provide a common frame for the currently quite fragmented literature on HOM studies. Finally, we highlight the existing gaps in our understanding and suggest directions for future HOM research.
The Genomic Data Storage (GDS) format provides efficient storage and retrieval of genotypes measured by microarrays and sequencing. We developed GENESIS to perform various single- and ...aggregate-variant association tests using genotype data stored in GDS format. GENESIS implements highly flexible mixed models, allowing for different link functions, multiple variance components and phenotypic heteroskedasticity. GENESIS integrates cohesively with other R/Bioconductor packages to build a complete genomic analysis workflow entirely within the R environment.
https://bioconductor.org/packages/GENESIS; vignettes included.
Supplementary data are available at Bioinformatics online.
ABSTRACT
Population structure inference with genetic data has been motivated by a variety of applications in population genetics and genetic association studies. Several approaches have been proposed ...for the identification of genetic ancestry differences in samples where study participants are assumed to be unrelated, including principal components analysis (PCA), multidimensional scaling (MDS), and model‐based methods for proportional ancestry estimation. Many genetic studies, however, include individuals with some degree of relatedness, and existing methods for inferring genetic ancestry fail in related samples. We present a method, PC‐AiR, for robust population structure inference in the presence of known or cryptic relatedness. PC‐AiR utilizes genome‐screen data and an efficient algorithm to identify a diverse subset of unrelated individuals that is representative of all ancestries in the sample. The PC‐AiR method directly performs PCA on the identified ancestry representative subset and then predicts components of variation for all remaining individuals based on genetic similarities. In simulation studies and in applications to real data from Phase III of the HapMap Project, we demonstrate that PC‐AiR provides a substantial improvement over existing approaches for population structure inference in related samples. We also demonstrate significant efficiency gains, where a single axis of variation from PC‐AiR provides better prediction of ancestry in a variety of structure settings than using 10 (or more) components of variation from widely used PCA and MDS approaches. Finally, we illustrate that PC‐AiR can provide improved population stratification correction over existing methods in genetic association studies with population structure and relatedness.
Abstract
Social life requires making inferences about other people. What information do perceivers spontaneously draw upon to make such inferences? Here, we test 4 major theories of person ...perception, and 1 synthetic theory that combines their features, to determine whether the dimensions of such theories can serve as bases for describing patterns of neural activity during mentalizing. While undergoing functional magnetic resonance imaging, participants made social judgments about well-known public figures. Patterns of brain activity were then predicted using feature encoding models that represented target people's positions on theoretical dimensions such as warmth and competence. All 5 theories of person perception proved highly accurate at reconstructing activity patterns, indicating that each could describe the informational basis of mentalizing. Cross-validation indicated that the theories robustly generalized across both targets and participants. The synthetic theory consistently attained the best performance-approximately two-thirds of noise ceiling accuracy--indicating that, in combination, the theories considered here can account for much of the neural representation of other people. Moreover, encoding models trained on the present data could reconstruct patterns of activity associated with mental state representations in independent data, suggesting the use of a common neural code to represent others' traits and states.
Inhibition of muscleblind-like (MBNL) activity due to sequestration by microsatellite expansion RNAs is a major pathogenic event in the RNA-mediated disease myotonic dystrophy (DM). Although MBNL1 ...and MBNL2 bind to nascent transcripts to regulate alternative splicing during muscle and brain development, another major binding site for the MBNL protein family is the 3′ untranslated region of target RNAs. Here, we report that depletion of Mbnl proteins in mouse embryo fibroblasts leads to misregulation of thousands of alternative polyadenylation events. HITS-CLIP and minigene reporter analyses indicate that these polyadenylation switches are a direct consequence of MBNL binding to target RNAs. Misregulated alternative polyadenylation also occurs in skeletal muscle in a mouse polyCUG model and human DM, resulting in the persistence of neonatal polyadenylation patterns. These findings reveal an additional developmental function for MBNL proteins and demonstrate that DM is characterized by misregulation of pre-mRNA processing at multiple levels.
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•Microsatellite CUG and CCUG expansion RNAs sequester MBNL proteins•MBNL proteins regulate alternative polyadenylation•MBNL loss induces a reversion to fetal polyadenylation patterns•Abnormal polyadenylation occurs in the RNA-mediated disease myotonic dystrophy
In the microsatellite expansion disorder myotonic dystrophy (DM), previous studies have implicated RNA splicing dysregulation as the major molecular signature associated with this disease. In this issue of Molecular Cell, Batra et al. demonstrate that alternative polyadenylation is also profoundly affected in DM.
Adolescents may not receive the sleep they need. New media technology and new, popular energy drinks may be implicated in sleep deficits. In this pilot study we quantified nighttime technology use ...and caffeine consumption to determine effects on sleep duration and daytime behaviors in adolescents. We hypothesized that with increased technology use, adolescents increase caffeine consumption, resulting in insufficient sleep duration.
Subjects were recruited from a pediatric office in a proximal suburb of Philadelphia, Pennsylvania. Inclusion criteria for this study were middle and high school subjects aged 12 to 18 years old. The questionnaire, Adolescent Sleep, Caffeine Intake, and Technology Use, was developed by the investigators to measure adolescents' intake of caffeinated drinks, use of nighttime media-related technology, and sleep behaviors. Descriptive statistics characterized the subjects, their caffeine and technology use, and sleep variables. Regression models assessed the relationships between caffeine, technology use, and sleep variables, having adjusted for age, race, gender, and BMI.
Sleep was significantly related to the multitasking index. Teenagers getting 8 to 10 hours of sleep on school nights tended to have 1.5- to 2-fold lower multitasking indices compared with those getting less sleep. Thirty-three percent of the teenagers reported falling asleep during school. Caffeine consumption tended to be 76% higher by those who fell asleep. The log-transformed multitasking index was significantly related to falling asleep during school and with difficulties falling asleep on weeknights.
Many adolescents used multiple forms of technology late into the night and concurrently consumed caffeinated beverages. Subsequently, their ability to stay alert and fully functional throughout the day was impaired by excessive daytime sleepiness. Future studies should measure more than television hours when evaluating the impact of nighttime activities on sleep patterns in adolescents.
Linear mixed models (LMMs) are widely used in genome-wide association studies (GWASs) to account for population structure and relatedness, for both continuous and binary traits. Motivated by the ...failure of LMMs to control type I errors in a GWAS of asthma, a binary trait, we show that LMMs are generally inappropriate for analyzing binary traits when population stratification leads to violation of the LMM’s constant-residual variance assumption. To overcome this problem, we develop a computationally efficient logistic mixed model approach for genome-wide analysis of binary traits, the generalized linear mixed model association test (GMMAT). This approach fits a logistic mixed model once per GWAS and performs score tests under the null hypothesis of no association between a binary trait and individual genetic variants. We show in simulation studies and real data analysis that GMMAT effectively controls for population structure and relatedness when analyzing binary traits in a wide variety of study designs.
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