775 research outputs found
An experimental study of steel fiber-reinforced high-strength concrete slender columns under cyclic loading
Structural engineers usually limit the use of HSC columns to seismic active zones because of their britle behavior in comparison with NSC, even though it presents advantages both in terms of mechanics and durability. A possible solution to improve the ductile behavior of HSC columns is the use of transverse reinforcement and steel fibers simultaneously.
In addition, the use of HSC makes the design of more slender columns possible, with the consequent increase of second-order effects. However, there are few experimental tests on columns of medium slenderness (between 5 and 10) subjected to cyclic loads including or excluding steel fibers.
This article presents experimental research work on the behavior of slender columns subjected to combined constant compression and cyclic lateral loads. Fifteen tests were carried out in order to study the behavior of such elements.
The following variables were studied: concrete strength, slenderness, axial load level, transverse reinforcement ratio, and volumetric steel-fiber ratio. The maximum load and deformation capacity of the columns were analyzed. The fact that the inclusion of steel fibers into the concrete mixture increases the deformation capacity was verified. Moreover, a minimum transverse reinforcement is required in order to improve the effectiveness of the steel fibers with no significant decrease in the carrying capacity under cyclic loading. The inclusion of steel fibers in HSC can ensure similar ductility values to those of NSC. It was shown that slenderness influences the deformation capacity.Structural engineers usually limit the use of HSC columns to seismic active zones because of their britle behavior in comparison with NSC, even though it presents advantages both in terms of mechanics and durability. A possible solution to improve the ductile behavior of HSC columns is the use of transverse reinforcement and steel fibers simultaneously.
In addition, the use of HSC makes the design of more slender columns possible, with the consequent increase of second-order effects. However, there are few experimental tests on columns of medium slenderness (between 5 and 10) subjected to cyclic loads including or excluding steel fibers.
This article presents experimental research work on the behavior of slender columns subjected to combined constant compression and cyclic lateral loads. Fifteen tests were carried out in order to study the behavior of such elements.
The following variables were studied: concrete strength, slenderness, axial load level, transverse reinforcement ratio, and volumetric steel-fiber ratio. The maximum load and deformation capacity of the columns were analyzed. The fact that the inclusion of steel fibers into the concrete mixture increases the deformation capacity was verified. Moreover, a minimum transverse reinforcement is required in order to improve the effectiveness of the steel fibers with no significant decrease in the carrying capacity under cyclic loading. The inclusion of steel fibers in HSC can ensure similar ductility values to those of NSC. It was shown that slenderness influences the deformation capacity
Behaviour of steel-fibre-reinforced normal-strength concrete slender columns under cyclic loading
The inclusion of ductility requirements is necessary to guarantee a safety design of concrete structures subjected to unexpected and/or reversal loads. It is important to outline that plastic hinges may develop in columns of reinforced concrete buildings, especially in column-foundation joints. The deformation capacity of the column depends on its slenderness. However, for the case of cyclic loading, few experimental tests of normal and fibre-reinforced concrete columns in the range of medium slenderness (between 5 and 10) have been performed. This paper presents an experimental research work on the behavior of slender columns subjected to combinations of constant axial and lateral cyclic loads. In order to study the behavior of this type of elements fourteen experimental tests are performed. The experimental results make it possible to calibrate numerical models, as well as, to validate simplified methods. The following variables are studied: slenderness, axial load level, volumetric transverse reinforcement ratio, and volumetric steel-fibre ratio. The maximum load and deformation capacity of the columns has been analyzed. It is interesting to note that ductility depends on the four tested variables analyzed. Moreover, the inclusion of steel-fibres into the concrete mixture increases the deformation capacity. In order to improve the steel fibres effectiveness the inclusion of a minimum transverse reinforcement is required. Thus, the column behavior suffers moderate strength losses due to cyclic loads. Finally, slenderness influences the deformation capacity if second-order effects are important, the cross-section has a ductile behavior, and materials capacity is reachedThe inclusion of ductility requirements is necessary to guarantee a safety design of concrete structures subjected to unexpected and/or reversal loads. It is important to outline that plastic hinges may develop in columns of reinforced concrete buildings, especially in column-foundation joints. The deformation capacity of the column depends on its slenderness. However, for the case of cyclic loading, few experimental tests of normal and fibre-reinforced concrete columns in the range of medium slenderness (between 5 and 10) have been performed. This paper presents an experimental research work on the behavior of slender columns subjected to combinations of constant axial and lateral cyclic loads. In order to study the behavior of this type of elements fourteen experimental tests are performed. The experimental results make it possible to calibrate numerical models, as well as, to validate simplified methods. The following variables are studied: slenderness, axial load level, volumetric transverse reinforcement ratio, and volumetric steel-fibre ratio. The maximum load and deformation capacity of the columns has been analyzed. It is interesting to note that ductility depends on the four tested variables analyzed. Moreover, the inclusion of steel-fibres into the concrete mixture increases the deformation capacity. In order to improve the steel fibres effectiveness the inclusion of a minimum transverse reinforcement is required. Thus, the column behavior suffers moderate strength losses due to cyclic loads. Finally, slenderness influences the deformation capacity if second-order effects are important, the cross-section has a ductile behavior, and materials capacity is reache
The Role of Sphingomyelin and Ceramide in Motor Neuron Diseases
Amyotrophic Lateral Sclerosis (ALS), Spinal Bulbar Muscular Atrophy (SBMA), and Spinal Muscular Atrophy (SMA) are motor neuron diseases (MNDs) characterised by progressive motor neuron degeneration, weakness and muscular atrophy. Lipid dysregulation is well recognised in each of these conditions and occurs prior to neurodegeneration. Several lipid markers have been shown to predict prognosis in ALS. Sphingolipids are complex lipids enriched in the central nervous system and are integral to key cellular functions including membrane stability and signalling pathways, as well as being mediators of neuroinflammation and neurodegeneration. This review highlights the metabolism of sphingomyelin (SM), the most abundant sphingolipid, and of its metabolite ceramide, and its role in the pathophysiology of neurodegeneration, focusing on MNDs. We also review published lipidomic studies in MNDs. In the 13 studies of patients with ALS, 12 demonstrated upregulation of multiple SM species and 6 demonstrated upregulation of ceramides. SM species also correlated with markers of clinical progression in five of six studies. These data highlight the potential use of SM and ceramide as biomarkers in ALS. Finally, we review potential therapeutic strategies for targeting sphingolipid metabolism in neurodegeneration
Mutations in CHMP2B in lower motor neuron predominant amyotrophic lateral sclerosis (ALS)
Background: Amyotrophic lateral sclerosis (ALS), a common late-onset neurodegenerative disease, is associated with fronto-temporal dementia (FTD) in 3-10% of patients. A mutation in CHMP2B was recently identified in a Danish pedigree with autosomal dominant FTD. Subsequently, two unrelated patients with familial ALS, one of whom also showed features of FTD, were shown to carry missense mutations in CHMP2B. The initial aim of this study was to determine whether mutations in CHMP2B contribute more broadly to ALS pathogenesis.
Methodology/Principal Findings: Sequencing of CHMP2B in 433 ALS cases from the North of England identified 4 cases carrying 3 missense mutations, including one novel mutation, p. Thr104Asn, none of which were present in 500 neurologically normal controls. Analysis of clinical and neuropathological data of these 4 cases showed a phenotype consistent with the lower motor neuron predominant (progressive muscular atrophy (PMA)) variant of ALS. Only one had a recognised family history of ALS and none had clinically apparent dementia. Microarray analysis of motor neurons from CHMP2B cases, compared to controls, showed a distinct gene expression signature with significant differential expression predicting disassembly of cell structure; increased calcium concentration in the ER lumen; decrease in the availability of ATP; down-regulation of the classical and p38 MAPK signalling pathways, reduction in autophagy initiation and a global repression of translation. Transfection of mutant CHMP2B into HEK-293 and COS-7 cells resulted in the formation of large cytoplasmic vacuoles, aberrant lysosomal localisation demonstrated by CD63 staining and impairment of autophagy indicated by increased levels of LC3-II protein. These changes were absent in control cells transfected with wild-type CHMP2B.
Conclusions/Significance: We conclude that in a population drawn from North of England pathogenic CHMP2B mutations are found in approximately 1% of cases of ALS and 10% of those with lower motor neuron predominant ALS. We provide a body of evidence indicating the likely pathogenicity of the reported gene alterations. However, absolute confirmation of pathogenicity requires further evidence, including documentation of familial transmission in ALS pedigrees which might be most fruitfully explored in cases with a LMN predominant phenotype
Guest Editorial
This is an editorial which introduces original papers produced on the theme of the supervision of social work practiceThis is an Accepted Manuscript of an article published by Taylor & Francis in Practice: Social Work in Action on September 2015, available online: http://dx.doi.org/10.1080/09503153.2015.1048053This guest editorial introduces the special edition on the supervision of social work practic
The reduced genome of the parasitic microsporidian Enterocytozoon bieneusi lacks genes for core carbon metabolism
© The Authors, 2010. This article is distributed under the terms of the Creative Commons Attribution-Noncommercial 2.5 License. The definitive version was published in Genome Biology and Evolution 2 (2010): 304, doi:10.1093/gbe/evq022.Reduction of various biological processes is a hallmark of the parasitic lifestyle. Generally, the more intimate the association between parasites and hosts the stronger the parasite relies on its host's physiology for survival and reproduction. However, some systems have been held to be indispensable, for example, the core pathways of carbon metabolism that produce energy from sugars. Even the most hardened anaerobes that lack oxidative phosphorylation and the tricarboxylic acid cycle have retained glycolysis and some downstream means to generate ATP. Here we describe the deep-coverage genome resequencing of the pathogenic microsporidiian, Enterocytozoon bieneusi, which shows that this parasite has crossed this line and abandoned complete pathways for the most basic carbon metabolism. Comparing two genome sequence surveys of E. bieneusi to genomic data from four other microsporidia reveals a normal complement of 353 genes representing 30 functional pathways in E. bieneusi, except that only 2 out of 21 genes collectively involved in glycolysis, pentose phosphate, and trehalose metabolism are present. Similarly, no genes encoding proteins involved in the processing of spliceosomal introns were found. Altogether, E. bieneusi appears to have no fully functional pathway to generate ATP from glucose. Therefore, this intracellular parasite relies on transporters to import ATP from its host.This work was supported by grants from the Canadian
Institutes for Health Research (MOP-84265), the National
Institutes of Health (NIH AI31788, R21 AI52792, and R21
AI064118), and the National Science Foundation (MCB-
0135272). N.C. is a Scholar of the Canadian Institute for
Advanced Research and is supported by a fellowship from
the Swiss National Science Foundation (NSF) (PA00P3-
124166). D.E. is supported by the Swiss NSF. P.J.K. is a Fellow
of the Canadian Institute for Advanced Research and
a Senior Scholar of the Michael Smith Foundation for Health
Research
Estudio teórico de capacidad de deformación de soportes esbeltos de hormigón armado con fibras de acero sometidos a esfuerzos combinados de axil y carga lateral
El estudio de la ductilidad es muy importante en elementos estructurales sometidos a esfuerzos combinados, ya que nos determina la capacidad de resistencia y a la deformación. Actualmente son escasos los ensayos experimentales para el estudio de soportes esbeltos sometidos a carga axial y carga lateral cÃclica, donde también hay carencia de estudios con respecto a hormigones de alta resistencia y adicion de fibras metálicas (Caballero-Morrison et al (2011)[5]). Se ha desarrollado un modelo numérico utilizando el software Opensees (http://opensees.berkeley.edu). Opensees es una herramienta de simulación disponibles en la Red para la simulación de IngenierÃa SÃsmica (Nees). En el análisis numérico se consideran las leyes constitutivas de hormigón reforzado con fibras confinados y no confinados bajo cargas cÃclicas, y las leyes constitutivas para las barras de acero bajo cargas cÃclicas y sometido a pandeo. Se ha realizado un estudio teórico de comportamiento inelástico de soportes esbeltos de hormigón definiéndose un modelo numérico en Opensees; dicho modelo ha sido calibrado con 25 ensayos experimentales propios. Los parámetros de estudio utilizados son: el nivel de axil, esbeltez a cortante, resistencia del hormigón, la cuantÃa de la armadura transversal, el tamaño de la sección y la adición de fibras metálicas en la masa del hormigón.El estudio de la ductilidad es muy importante en elementos estructurales sometidos a esfuerzos combinados, ya que nos determina la capacidad de resistencia y a la deformación. Actualmente son escasos los ensayos experimentales para el estudio de soportes esbeltos sometidos a carga axial y carga lateral cÃclica, donde también hay carencia de estudios con respecto a hormigones de alta resistencia y adicion de fibras metálicas (Caballero-Morrison et al (2011)[5]). Se ha desarrollado un modelo numérico utilizando el software Opensees (http://opensees.berkeley.edu). Opensees es una herramienta de simulación disponibles en la Red para la simulación de IngenierÃa SÃsmica (Nees). En el análisis numérico se consideran las leyes constitutivas de hormigón reforzado con fibras confinados y no confinados bajo cargas cÃclicas, y las leyes constitutivas para las barras de acero bajo cargas cÃclicas y sometido a pandeo. Se ha realizado un estudio teórico de comportamiento inelástico de soportes esbeltos de hormigón definiéndose un modelo numérico en Opensees; dicho modelo ha sido calibrado con 25 ensayos experimentales propios. Los parámetros de estudio utilizados son: el nivel de axil, esbeltez a cortante, resistencia del hormigón, la cuantÃa de la armadura transversal, el tamaño de la sección y la adición de fibras metálicas en la masa del hormigón
Comportamiento de soportes esbeltos de hormigón armado con fibras de acero sometidos a esfuerzos combinados de axil y carga lateral cÃclica
La ductilidad es un indicador de la capacidad de deformación en estructuras sometidas a esfuerzos combinados de axil y carga lateral cÃclica. El elemento estructural sometido a estos esfuerzos debe ser capaz de absorber y de disipar la energÃa sin que se produzca una significativa perdida de capacidad resistente. En la actualidad, las normativas para el diseño sÃsmico estructural, (EC-8 (2004)[4], ACI-318(11)[1]) especifican la disposición de la cuantÃa de armadura transversal a disponer en las zonas crÃticas susceptibles de albergar una rótula plástica. Para niveles altos de axil es necesario disponer una cuantÃa importante de armadura transversal. Dicha cuantÃa puede suponer problemas durante la puesta en obra del hormigón. La literatura técnica señala como una posible solución para mejorar la ductilidad de este tipo de soportes utilizar hormigón con fibras en su masa. Por otro lado, los efectos de segundo orden que se producen en los soportes influyen en la capacidad de deformación (Bae y Bayrak (2006)[8]); y en la literatura técnica son escasos los ensayos experimentales de soportes cuya esbeltez sea superior a 6.5. Por tales razones se han realizado 25 ensayos experimentales donde se estudian parámetros como la resistencia del hormigón, la esbeltez geométrica de la pieza, la cuantÃa de armadura tranversal, el nivel de axil reducido, la sección transversal y la adición de fibras metálicas en la masa del hormigón. Estos ensayos tienen como objetivo conocer la capacidad de deformación y de resistencia sometidos a una carga axial y carga lateral cÃclica según los parámetros mencionados anteriormente; y además han de servir para calibrar modelos numéricos y validar métodos simplificados.La ductilidad es un indicador de la capacidad de deformación en estructuras sometidas a esfuerzos combinados de axil y carga lateral cÃclica. El elemento estructural sometido a estos esfuerzos debe ser capaz de absorber y de disipar la energÃa sin que se produzca una significativa perdida de capacidad resistente. En la actualidad, las normativas para el diseño sÃsmico estructural, (EC-8 (2004)[4], ACI-318(11)[1]) especifican la disposición de la cuantÃa de armadura transversal a disponer en las zonas crÃticas susceptibles de albergar una rótula plástica. Para niveles altos de axil es necesario disponer una cuantÃa importante de armadura transversal. Dicha cuantÃa puede suponer problemas durante la puesta en obra del hormigón. La literatura técnica señala como una posible solución para mejorar la ductilidad de este tipo de soportes utilizar hormigón con fibras en su masa. Por otro lado, los efectos de segundo orden que se producen en los soportes influyen en la capacidad de deformación (Bae y Bayrak (2006)[8]); y en la literatura técnica son escasos los ensayos experimentales de soportes cuya esbeltez sea superior a 6.5. Por tales razones se han realizado 25 ensayos experimentales donde se estudian parámetros como la resistencia del hormigón, la esbeltez geométrica de la pieza, la cuantÃa de armadura tranversal, el nivel de axil reducido, la sección transversal y la adición de fibras metálicas en la masa del hormigón. Estos ensayos tienen como objetivo conocer la capacidad de deformación y de resistencia sometidos a una carga axial y carga lateral cÃclica según los parámetros mencionados anteriormente; y además han de servir para calibrar modelos numéricos y validar métodos simplificados
Drivers of care costs and quality in the last three months of life among older people receiving palliative care:a multinational mortality follow-back survey across England, Ireland and the USA
11β-HSD1 suppresses cardiac fibroblast CXCL2, CXCL5 and neutrophil recruitment to the heart post MI
We have previously demonstrated that neutrophil recruitment to the heart following myocardial infarction (MI) is enhanced in mice lacking 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) that regenerates active glucocorticoid within cells from intrinsically inert metabolites. The present study aimed to identify the mechanism of regulation. In a mouse model of MI, neutrophil mobilization to blood and recruitment to the heart were higher in 11β-HSD1-deficient (Hsd11b1(-)(/)(-) ) relative to wild-type (WT) mice, despite similar initial injury and circulating glucocorticoid. In bone marrow chimeric mice, neutrophil mobilization was increased when 11β-HSD1 was absent from host cells, but not when absent from donor bone marrow-derived cells. Consistent with a role for 11β-HSD1 in 'host' myocardium, gene expression of a subset of neutrophil chemoattractants, including the chemokines Cxcl2 and Cxcl5, was selectively increased in the myocardium of Hsd11b1(-)(/)(-) mice relative to WT. SM22α-Cre directed disruption of Hsd11b1 in smooth muscle and cardiomyocytes had no effect on neutrophil recruitment. Expression of Cxcl2 and Cxcl5 was elevated in fibroblast fractions isolated from hearts of Hsd11b1(-)(/)(-) mice post MI and provision of either corticosterone or of the 11β-HSD1 substrate, 11-dehydrocorticosterone, to cultured murine cardiac fibroblasts suppressed IL-1α-induced expression of Cxcl2 and Cxcl5 These data identify suppression of CXCL2 and CXCL5 chemoattractant expression by 11β-HSD1 as a novel mechanism with potential for regulation of neutrophil recruitment to the injured myocardium, and cardiac fibroblasts as a key site for intracellular glucocorticoid regeneration during acute inflammation following myocardial injury
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