894 research outputs found
Experimental behaviour of a steel structure under natural fire
Current design codes for fire resistance of structures are based on isolated member tests subjected to standard fire conditions. Such tests do not reflect the behaviour of a complete building under either normal temperature or fire conditions. Many aspects of behaviour occur due to the interaction between members and cannot be predicted or observed in tests of isolated elements. Performance of real structures subject to real fires is often much better than that predicted from standard tests due to structural continuity and the provision of alternative load paths.http://www.sciencedirect.com/science/article/B6V37-4KN5C4D-1/1/8f781d0c96159d54029bef7c9ec451b
Experimental behaviour of a steel structure under natural fire
Current design codes for fire resistance of structures are based on isolated member tests subjected to standard fire conditions. Such tests do not reflect the behaviour of a complete building under either normal temperature or fire conditions. Many aspects of behaviour occur due to the interaction between members and cannot be predicted or observed in tests of isolated elements. Performance of real structures subject to real fires is often much better than that predicted from standard tests due to structural continuity and the provision of alternative load paths.http://www.sciencedirect.com/science/article/B6V37-4KN5C4D-1/1/8f781d0c96159d54029bef7c9ec451b
Lymphocyte gene expression signatures from patients and mouse models of hereditary hemochromatosis reveal a function of HFE as a negative regulator of CD8+ T-lymphocyte activation and differentiation in vivo
Abnormally low CD8+ T-lymphocyte numbers is characteristic of some patients with hereditary hemochromatosis (HH), a MHC-linked disorder of iron overload. Both environmental and genetic components are known to influence CD8+ T-lymphocyte homeostasis but the role of the HH associated protein HFE is still insufficiently understood. Genome-wide expression profiling was performed in peripheral blood CD8+ T lymphocytes from HH patients selected according to CD8+ T-lymphocyte numbers and from Hfe-/- mice maintained either under normal or high iron diet conditions. In addition, T-lymphocyte apoptosis and cell cycle progression were analyzed by flow cytometry in HH patients. HH patients with low CD8+ T-lymphocyte numbers show a differential expression of genes related to lymphocyte differentiation and maturation namely CCR7, LEF1, ACTN1, NAA50, P2RY8 and FOSL2, whose expression correlates with the relative proportions of naïve, central and effector memory subsets. In addition, expression levels of LEF1 and P2RY8 in memory cells as well as the proportions of CD8+ T cells in G2/M cell cycle phase are significantly different in HH patients compared to controls. Hfe-/- mice do not show alterations in CD8+ T-lymphocyte numbers but differential gene response patterns. We found an increased expression of S100a8 and S100a9 that is most pronounced in high iron diet conditions. Similarly, CD8+ T lymphocytes from HH patients display higher S100a9 expression both at the mRNA and protein level. Altogether, our results support a role for HFE as a negative regulator of CD8+ T-lymphocyte activation. While the activation markers S100a8 and S100a9 are strongly increased in CD8+ T cells from both, Hfe-/- mice and HH patients, a differential profile of genes related to differentiation/maturation of CD8+ T memory cells is evident in HH patients only. This supports the notion that HFE contributes, at least in part, to the generation of low peripheral blood CD8+ T lymphocytes in HH
Mixing of Active and Sterile Neutrinos
We investigate mixing of neutrinos in the MSM (neutrino Minimal Standard
Model), which is the MSM extended by three right-handed neutrinos. Especially,
we study elements of the mixing matrix between three
left-handed neutrinos () and two sterile
neutrinos () which are responsible to the seesaw mechanism
generating the suppressed masses of active neutrinos as well as the generation
of the baryon asymmetry of the universe (BAU). It is shown that
can be suppressed by many orders of magnitude compared with
and , when the Chooz angle is large in the
normal hierarchy of active neutrino masses. We then discuss the neutrinoless
double beta decay in this framework by taking into account the contributions
not only from active neutrinos but also from all the three sterile neutrinos.
It is shown that and give substantial, destructive contributions
when their masses are smaller than a few 100 MeV, and as a results receive no stringent constraint from the current bounds on such decay.
Finally, we discuss the impacts of the obtained results on the direct searches
of in meson decays for the case when are lighter than pion
mass. We show that there exists the allowed region for with such
small masses in the normal hierarchy case even if the current bound on the
lifetimes of from the big bang nucleosynthesis is imposed. It is also
pointed out that the direct search by using and might miss such since the branching ratios can be
extremely small due to the cancellation in , but the search by
can cover the whole allowed region by improving the
measurement of the branching ratio by a factor of 5.Comment: 30 pages, 32 figure
Popular attitudes to memory, the body, and social identity : the rise of external commemoration in Britain, Ireland, and New England
A comparative analysis of samples of external memorials from burial grounds in Britain, Ireland and New England reveals a widespread pattern of change in monument style and content, and exponential growth in the number of permanent memorials from the 18th century onwards. Although manifested in regionally distinctive styles on which most academic attention has so far been directed, the expansion reflects global changes in social relationships and concepts of memory and the body. An archaeological perspective reveals the importance of external memorials in articulating these changing attitudes in a world of increasing material consumption
Neutrinoless double beta decay in seesaw models
We study the general phenomenology of neutrinoless double beta decay in
seesaw models. In particular, we focus on the dependence of the neutrinoless
double beta decay rate on the mass of the extra states introduced to account
for the Majorana masses of light neutrinos. For this purpose, we compute the
nuclear matrix elements as functions of the mass of the mediating fermions and
estimate the associated uncertainties. We then discuss what can be inferred on
the seesaw model parameters in the different mass regimes and clarify how the
contribution of the light neutrinos should always be taken into account when
deriving bounds on the extra parameters. Conversely, the extra states can also
have a significant impact, cancelling the Standard Model neutrino contribution
for masses lighter than the nuclear scale and leading to vanishing neutrinoless
double beta decay amplitudes even if neutrinos are Majorana particles. We also
discuss how seesaw models could reconcile large rates of neutrinoless double
beta decay with more stringent cosmological bounds on neutrino masses.Comment: 34 pages, 5 eps figures and 1 axodraw figure. Final version published
in JHEP. NME results available in Appendi
A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci
The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function
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