450 research outputs found

    The Influence of Mechanical Stratigraphy on Thrust-Ramp Nucleation and Propagation of Thrust Faults

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    Our current understanding of thrust fault kinematics predicts that thrust faults nucleate on low angle, weak surfaces before they propagate upward and forms a higher angle ramp. While this classic kinematic and geometric model serves well in some settings, it does not fully consider the observations of footwall deformation beneath some thrust faults. We examine an alternative end-member model of thrust fault formation called “ramp-first” fault formation. This model hypothesizes that in mechanically layered rocks, thrust ramps nucleate in the structurally strong units, and that faults can propagate both upward and downward into weaker units forming folds at both fault tips. To explore this model, we integrate traditional structural geology field methods, two dimensional cross section reconstructions, and finite element modeling. Field data and retro-deformable cross sections suggest that thrust faults at the Ketobe Knob, in Utah nucleated in strong layers and propagated upward and downward creating folds in weak layers. These findings support the hypothesis that thrust faults and associated folds at the Ketobe Knob developed in accordance with the ramp-first kinematic model.We can apply this understanding of the mechanics behind thrust fault nucleation and propagation in mechanically layered stratigraphy to a wide range of geological disciplines like structural geology and tectonics, seismology, and petroleum geology. By incorporating our knowledge of lithology into fault models, geologists are more likely to correctly interpret structures with limited data sets

    The Impact of Inter-Bed Cohesion on Fold-Related Fracture Development, Stillwell Anticline, West Texas (USA)

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    The interpretation of fracture networks in contractional folds is challenging due to the range of factors that control fracture formation. We use outcrop-based analysis of fractures in plan-view pavements and in a 9-bed cross-sectional exposure to evaluate the fracture system within Cretaceous limestone layers of a Laramide fold in west Texas, the Stillwell anticline. Opening-mode extension fractures (veins) at high angles to bedding dominate the fracture population, although shear fractures and faults cut bedding at low angles within the forelimb. Analysis of extension fractures reveals NW-striking axial parallel and NE-striking axial-perpendicular fracture sets interpreted to have formed during contractional folding, a third N-striking fracture set formed during subsequent Basin and Range extension, and a fourth ESE-striking fracture formed due to unloading during exhumation. Fracture fill textures suggest that many fracture apertures increased during exhumation. The relative abundances of the four fracture sets and the intensity of each set vary from bed to bed in cross section. Because beds display no significant differences in mechanical strength and there is no correlation between bed thickness and fracture intensity, we attribute this bed-to-bed variability to differences in cohesion between beds. Bed decoupling, when combined with low extensional

    Increased susceptibility to repeated freeze-thaw cycles in Escherichia coli following long-term evolution in a benign environment

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    BACKGROUND: In order to study the dynamics of evolutionary change, 12 populations of E. coli B were serially propagated for 20,000 generations in minimal glucose medium at constant 37°C. Correlated changes in various other traits have been previously associated with the improvement in competitive fitness in the selective environment. This study examines whether these evolved lines changed in their ability to tolerate the stresses of prolonged freezing and repeated freeze-thaw cycles during adaptation to a benign environment. RESULTS: All 12 lines that evolved in the benign environment for 20,000 generations are more sensitive to freeze-thaw cycles than their ancestor. The evolved lines have an average mortality rate of 54% per daily cycle, compared to the ancestral rate of 34%. By contrast, there was no significant difference between the evolved lines and their ancestor in mortality during prolonged freezing. There was also some variability among the evolved lines in susceptibility to repeated freeze-thaw cycles. Those lines that had evolved higher competitive fitness in the minimal glucose medium at 37°C also had higher mortality during freeze-thaw cycles. This variability was not associated, however, with differences among lines in DNA repair functionality and mutability. CONCLUSION: The consistency of the evolutionary declines in freeze-thaw tolerance, the correlation between fitness in glucose medium at 37°C and mortality during freeze-thaw cycles, and the absence of greater declines in freeze-thaw survival among the hypermutable lines all indicate a trade-off between performance in minimal glucose medium at 37°C and the capacity to tolerate this stress. Analyses of the mutations that enhance fitness at 37°C may shed light on the physiological basis of this trade-off

    A LASSO-based approach to analyzing rare variants in genetic association studies

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    Genetic markers with rare variants are spread out in the genome, making it necessary and difficult to consider them in genetic association studies. Consequently, wisely combining rare variants into “composite” markers may facilitate meaningful analyses. In this paper, we propose a novel approach of analyzing rare variant data by incorporating the least absolute shrinkage and selection operator technique. We applied this method to the Genetic Analysis Workshop 17 data, and our results suggest that this new approach is promising. In addition, we took advantage of having 200 phenotype replications and assessed the performance of our approach by means of repeated classification tree analyses. Our method and analyses were performed without knowledge of the underlying simulating model. Our method identified 38 markers (in 65 genes) that are significantly associated with the phenotype Affected and correctly identified two causal genes, SIRT1 and PDGFD

    Systemic IL-12 Administration Alters Hepatic Dendritic Cell Stimulation Capabilities

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    The liver is an immunologically unique organ containing tolerogenic dendritic cells (DC) that maintain an immunosuppressive microenvironment. Although systemic IL-12 administration can improve responses to tumors, the effects of IL-12-based treatments on DC, in particular hepatic DC, remain incompletely understood. In this study, we demonstrate systemic IL-12 administration induces a 2–3 fold increase in conventional, but not plasmacytoid, DC subsets in the liver. Following IL-12 administration, hepatic DC became more phenotypically and functionally mature, resembling the function of splenic DC, but differed as compared to their splenic counterparts in the production of IL-12 following co-stimulation with toll-like receptor (TLR) agonists. Hepatic DCs from IL-12 treated mice acquired enhanced T cell proliferative capabilities similar to levels observed using splenic DCs. Furthermore, IL-12 administration preferentially increased hepatic T cell activation and IFNγ expression in the RENCA mouse model of renal cell carcinoma. Collectively, the data shows systemic IL-12 administration enables hepatic DCs to overcome at least some aspects of the inherently suppressive milieu of the hepatic environment that could have important implications for the design of IL-12-based immunotherapeutic strategies targeting hepatic malignancies and infections

    Views on and experiences of electronic cigarettes: a qualitative study of women who are pregnant or have recently given birth.

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    Background Electronic cigarettes (ECs) are increasingly used for reducing or stopping smoking, with some studies showing positive outcomes. However, little is known about views on ECs during pregnancy or postpartum and previous studies have nearly all been conducted in the US and have methodological limitations, such as not distinguishing between smokers and ex/non-smokers. A greater understanding of this topic will help to inform both clinicians and EC interventions. We elicited views and experiences of ECs among UK pregnant or recently pregnant women. Methods We conducted semi-structured telephone interviews, using topic guides, with pregnant or recently pregnant women, who were current or recent ex-smokers. To ensure broad views of ECs were obtained, recruitment was from several geographical locations and via various avenues of recruitment. This included stop smoking services, antenatal and health visitor clinics, a pregnancy website and an informal network. Participants were 15 pregnant and 15 postpartum women, including nine current EC users, 11 ex-users, and 10 never-users. Five women who were interviewed in pregnancy were later interviewed in postpartum to explore if their views had changed. Audio data was transcribed verbatim and framework analysis was applied. Results Five main themes emerged: motivations for use (e.g., for stopping or reducing smoking), social stigma (e.g., avoiding use in public, preferring ‘discrete’ NRT), using the EC (e.g., mostly used at home); consumer aspects (e.g., limited advice available), and harm perceptions (e.g., viewed as less harmful than smoking; concerns about safety and addiction). Conclusions ECs were viewed positively by some pregnant and postpartum women and seen as less harmful than smoking and useful as aids for reducing and stopping smoking. However, due to perceived social stigma, some women feel uncomfortable using ECs in public, especially during pregnancy, and had concerns about safety and nicotine dependence. Health professionals and designers of EC interventions need to provide women with up-to-date and consistent information and advice about safety and dependence, as well as considering the influence of social stigma

    A One Base Pair Deletion in the Canine ATP13A2 Gene Causes Exon Skipping and Late-Onset Neuronal Ceroid Lipofuscinosis in the Tibetan Terrier

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    Neuronal ceroid lipofuscinosis (NCL) is a progressive neurodegenerative disease characterized by brain and retinal atrophy and the intracellular accumulation of autofluorescent lysosomal storage bodies resembling lipofuscin in neurons and other cells. Tibetan terriers show a late-onset lethal form of NCL manifesting first visible signs at 5–7 years of age. Genome-wide association analyses for 12 Tibetan-terrier-NCL-cases and 7 Tibetan-terrier controls using the 127K canine Affymetrix SNP chip and mixed model analysis mapped NCL to dog chromosome (CFA) 2 at 83.71–84.72 Mb. Multipoint linkage and association analyses in 376 Tibetan terriers confirmed this genomic region on CFA2. A mutation analysis for 14 positional candidate genes in two NCL-cases and one control revealed a strongly associated single nucleotide polymorphism (SNP) in the MAPK PM20/PM21 gene and a perfectly with NCL associated single base pair deletion (c.1620delG) within exon 16 of the ATP13A2 gene. The c.1620delG mutation in ATP13A2 causes skipping of exon 16 presumably due to a broken exonic splicing enhancer motif. As a result of this mutation, ATP13A2 lacks 69 amino acids. All known 24 NCL cases were homozygous for this deletion and all obligate 35 NCL-carriers were heterozygous. In a sample of 144 dogs from eleven other breeds, the c.1620delG mutation could not be found. Knowledge of the causative mutation for late-onset NCL in Tibetan terrier allows genetic testing of these dogs to avoid matings of carrier animals. ATP13A2 mutations have been described in familial Parkinson syndrome (PARK9). Tibetan terriers with these mutations provide a valuable model for a PARK9-linked disease and possibly for manganese toxicity in synucleinopathies
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