871 research outputs found
Locking-free two-layer Timoshenko beam element with interlayer slip
A new locking-free strain-based finite element formulation for the numerical treatment of linear static analysis of two-layer planar composite beams with interlayer slip is proposed. In this formulation, the modified principle of virtual work is introduced as a basis for the finite element discretization. The linear kinematic equations are included into the principle by the procedure, similar to that of Lagrangian multipliers. A strain field vector remains the only unknown function to be interpolated in the finite element implementation of the principle. In contrast with some of the displacement-based and mixed finite element formulations of the composite beams with interlayer slip, the present formulation is completely locking-free. Hence, there are no shear and slip locking, poor convergence and stress oscillations in these finite elements. The generalization of the composite beam theory with the consideration of the Timoshenko beam theory for the individual component of a composite beam represents a substantial contribution in the field of analysis of non-slender composite beams with an interlayer slip. An extension of the present formulation to the non-linear material problems is straightforward. As only a few finite elements are needed to describe a composite beam with great precision, the new finite element formulations is perfectly suited for practical calculations. (c) 2007 Elsevier B.V. All rights reserved
Nephrogenic systemic fibrosis
Nephrogenic systemic fibrosis, initially called nephrogenic fibrosing dermopathy, has been strongly linked to exposure to gadolinium-based contrast media used in magnetic resonance imaging in patients with renal insufficiency. This review discusses recent advances in our understanding of the pathophysiology and clinical approach to patients with chronic kidney disease who require diagnostic imaging with gadolinium-based contrast media
Sinking Jelly-Carbon Unveils Potential Environmental Variability along a Continental Margin
Particulate matter export fuels benthic ecosystems in continental margins and the deep sea, removing carbon from the upper ocean. Gelatinous zooplankton biomass provides a fast carbon vector that has been poorly studied. Observational data of a large-scale benthic trawling survey from 1994 to 2005 provided a unique opportunity to quantify jelly-carbon along an entire continental margin in the Mediterranean Sea and to assess potential links with biological and physical variables. Biomass depositions were sampled in shelves, slopes and canyons with peaks above 1000 carcasses per trawl, translating to standing stock values between 0.3 and 1.4 mg C m2 after trawling and integrating between 30,000 and 175,000 m2 of seabed. The benthopelagic jelly-carbon spatial distribution from the shelf to the canyons may be explained by atmospheric forcing related with NAO events and dense shelf water cascading, which are both known from the open Mediterranean. Over the decadal scale, we show that the jelly-carbon depositions temporal variability paralleled hydroclimate modifications, and that the enhanced jelly-carbon deposits are connected to a temperature-driven system where chlorophyll plays a minor role. Our results highlight the importance of gelatinous groups as indicators of large-scale ecosystem change, where jelly-carbon depositions play an important role in carbon and energy transport to benthic systems
Evaluación de los efectos genotóxicos del herbicida 2,4-D en Piaractus mesopotamicus a través del test de micronúcleos
The herbicide 2,4-D is currently one of the most used agrochemicals in agriculture. The fish are target of contamination, these when being in contact with toxics develop later alterations that can be studied, reason why they are used as models in the evaluation of aquatic ecosystems. There is scarce information about the effects of these pesticides in fish. Because of this, the objective of this work was to evaluate the possible impact of a contamination with 2,4-D, in sub-lethal concentrations in Piaractus mesopotamicus, through the frequency of micronuclei (MN) and alterations in the shape of the nuclei (NMA) in peripheral blood erythrocytes in chronic conditions (70 days). Two trials were conducted, one with the herbicide 2,4-D pure (P) and another with a commercial formulation (2,4-D bitter amine) (FC). Each experience was composed of five aquariums with two specimens in each, where different concentrations of the pesticide were administered (1 ppm, 1.8 ppm, 3.2 ppm, 5.6 ppm and 10 ppm), and in another with well water (control). A total of 4000 cells per individual were analyzed. Through the test MN and NMA the presence of diverse nuclear alterations was evidenced. The mentioned test for P and dilutions 1 ppm, 1.8 ppm, 3.2 ppm, 5.6 ppm of FC did not show significant differences with the control, while the concentration of 10 ppm of FC differed statistically from its control, this could be due to additional components in FC.Los herbicidas están siendo abundantemente utilizados haciendo que los mismos no solo lleguen al organismo específico sino también contaminen el medio ambiente donde son empleados. El herbicida 2,4-D es en la actualidad uno de los agroquímicos más utilizado en la agricultura. Los peces son blanco de la contaminación, éstos al estar en contacto con tóxicos desarrollan posteriormente alteraciones que pueden ser estudiadas, por lo cual son utilizados como modelos en la evaluacion de ecosistemas acuáticos. Existe escasa información acerca de los efectos de estos pesticidas en peces, siendo el actual trabajo el primero en evaluar efectos crónicos. El objetivo de la presente investigación fue evaluar el posible impacto de una contaminación con 2,4-D en concentraciones subletales en Piaractus mesopotamicus, a través de la frecuencia de micronúcleos (MN) y de las alteraciones en la forma de los núcleos (NMA) en eritrocitos de sangre periférica en condiciones crónicas (70 días). Se realizaron dos ensayos, uno con el herbicida 2,4-D puro (P) y otro con una formulación comercial (2,4-D amina Sumargo) (FC). Cada experiencia estuvo compuesta por cinco acuarios con dos ejemplares en cada uno, donde se administraron difererentes concentraciones del plaguicida (1 ppm, 1,8 ppm, 3,2 ppm, 5,6 ppm y 10 ppm), y en otra con agua de pozo (control). Se analizó un total de 4000 células por individuo. A través del test MN y NMA se evidenció la presencia de diversas alteraciones nucleares. El mencionado test para P y las diluciones 1 ppm, 1,8 ppm, 3,2 ppm, 5,6 ppm de FC no mostraron diferencias significativas con el control, mientras que la concentración de 10 ppm de FC se diferenció estadísticamente de su control. El presente trabajo aporta luz de los potenciales efectos nocivos del 2,4-D en el medio ambiente y posibilita nuevos estudios prospectivos y retrospectivos
Functional Analysis of a Breast Cancer-Associated FGFR2 Single Nucleotide Polymorphism Using Zinc Finger Mediated Genome Editing
The authors thank Barts Charity for funding and Breast Cancer Campaign for funding the Barts Breast Tissue Bank
Regulators of genetic risk of breast cancer identified by integrative network analysis.
Genetic risk for breast cancer is conferred by a combination of multiple variants of small effect. To better understand how risk loci might combine, we examined whether risk-associated genes share regulatory mechanisms. We created a breast cancer gene regulatory network comprising transcription factors and groups of putative target genes (regulons) and asked whether specific regulons are enriched for genes associated with risk loci via expression quantitative trait loci (eQTLs). We identified 36 overlapping regulons that were enriched for risk loci and formed a distinct cluster within the network, suggesting shared biology. The risk transcription factors driving these regulons are frequently mutated in cancer and lie in two opposing subgroups, which relate to estrogen receptor (ER)(+) luminal A or luminal B and ER(-) basal-like cancers and to different luminal epithelial cell populations in the adult mammary gland. Our network approach provides a foundation for determining the regulatory circuits governing breast cancer, to identify targets for intervention, and is transferable to other disease settings.This work was funded by Cancer Research UK and the Breast Cancer Research Foundation. MAAC is funded by the National Research Council (CNPq) of Brazil. TEH held a fellowship from the US DOD Breast Cancer Research Program (W81XWH-11-1-0592) and is currently supported by an RAH Career Development Fellowship (Australia). TEH and WDT are funded by the NHMRC of Australia (NHMRC) (ID: 1008349 WDT; 1084416 WDT, TEH) and Cancer Australia/National Breast Cancer Foundation (ID 627229; WDT, TEH). BAJP is a Gibb Fellow of Cancer Research UK. We would like to acknowledge the support of The University of Cambridge, Cancer Research UK and Hutchison Whampoa Limited.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/ng.345
Avian mycobacteriosis in chickens from a rural area of Argentina
An outbreak of avian tuberculosis was detected in chickens from a rural area of Chaco Province, northeastern Argentina. The hens were emaciated and presented granulomatous lesions of various sizes throughout the internal organs. The lesions observed in three necropsied birds consisted of granulomas containing alcohol/acid-fast bacilli. All the lesions found were diagnosed histopathologically as tuberculosis, Mycobacterium avium subsp. avium were isolated from the cultures and confirmed by polymerase chain reaction techniques
Parallels, prescience and the past: analogical reasoning and contemporary international politics
Analogical reasoning has held a perpetual appeal to policymakers who have often drafted in historical metaphor as a mode of informing decision-making. However, this article contends that since the beginning of the ‘War on Terror’ we have arguably seen the rise of a more potent form of analogy, namely ones that are selected because they fulfil an ideological function. Analogical reasoning as a tool of rational decision-making has increasingly become replaced by analogical reasoning as a tool of trenchant ideologically-informed policy justification. This article addresses three key areas which map out the importance of analogical reasoning to an understanding of developments in contemporary international politics: the relationship between history and politics, in intellectual and policy terms; a critical assessment of the appeal that analogical reasoning holds for policymakers; and the development of a rationale for a more effective use of history in international public policymaking
Occupancy maps of 208 chromatin-associated proteins in one human cell type
Transcription factors are DNA-binding proteins that have key roles in gene regulation. Genome-wide occupancy maps of transcriptional regulators are important for understanding gene regulation and its effects on diverse biological processes. However, only a minority of the more than 1,600 transcription factors encoded in the human genome has been assayed. Here we present, as part of the ENCODE (Encyclopedia of DNA Elements) project, data and analyses from chromatin immunoprecipitation followed by high-throughput sequencing (ChIP–seq) experiments using the human HepG2 cell line for 208 chromatin-associated proteins (CAPs). These comprise 171 transcription factors and 37 transcriptional cofactors and chromatin regulator proteins, and represent nearly one-quarter of CAPs expressed in HepG2 cells. The binding profiles of these CAPs form major groups associated predominantly with promoters or enhancers, or with both. We confirm and expand the current catalogue of DNA sequence motifs for transcription factors, and describe motifs that correspond to other transcription factors that are co-enriched with the primary ChIP target. For example, FOX family motifs are enriched in ChIP–seq peaks of 37 other CAPs. We show that motif content and occupancy patterns can distinguish between promoters and enhancers. This catalogue reveals high-occupancy target regions at which many CAPs associate, although each contains motifs for only a minority of the numerous associated transcription factors. These analyses provide a more complete overview of the gene regulatory networks that define this cell type, and demonstrate the usefulness of the large-scale production efforts of the ENCODE Consortium
A copper-catalyzed asymmetric oxime propargylation enables the synthesis of the gliovirin tetrahydro-1,2-oxazine core
The bicyclic tetrahydro-1,2-oxazine subunit of gliovirin is synthesized through a diastereoselective copper-catalyzed cyclization of an N-hydroxyamino ester. Oxidative elaboration to the fully functionalized bicycle was achieved through a series of mild transformations. Central to this approach was the development of the first catalytic, enantioselective propargylation of an oxime to furnish a key N-hydroyxamino ester intermediate
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