2,620 research outputs found
Perforation resistance of aluminum/polyethylene sandwich structure
© 2016 Elsevier Ltd. Ballistic tests were performed on two types of polyethylene core sandwich structures (AA6082/LDPE/AA6082 and AA6082/UHMWPE/AA6082) to investigate their perforation resistance. Bulging and dishing deformation of layered plates were compared under low-velocity impact by hemispherical-nosed projectiles. Different impact failure mechanisms leading to perforation were revealed for laminates composed of a pair of aluminum alloy face sheets separated by a polyethylene interlayer. Using the finite element code Abaqus/Explicit, the perforation behavior and distribution of energy dissipation of each layer during penetration were simulated and analysed. The deformation resistance and anti-penetration properties of polyethylene core sandwich structures were compared with those of monolithic AA6082-T6 plates that had the same areal density. Although the polyethylene interlayer enlarged the plastic deformation zone of the back face, the polyethylene core sandwich structure was a little less effective than the monolithic Al alloy target at resisting hemispherical-nosed projectile impact.The authors gratefully acknowledge the Foundation of State Key Laboratory of Explosion Science and Technology of China under Grant No. KFJJ13-1Z, and Natural Science Foundation of China under Grant No. 11102023, 11172071
On the flexibility of the design of Multiple Try Metropolis schemes
The Multiple Try Metropolis (MTM) method is a generalization of the classical
Metropolis-Hastings algorithm in which the next state of the chain is chosen
among a set of samples, according to normalized weights. In the literature,
several extensions have been proposed. In this work, we show and remark upon
the flexibility of the design of MTM-type methods, fulfilling the detailed
balance condition. We discuss several possibilities and show different
numerical results
The effect of loading rate on the compression properties of carbon fibre-reinforced epoxy honeycomb structures
Using electric current to surpass the microstructure breakup limit
The elongated droplets and grains can break up into smaller ones. This process is driven by the interfacial free energy minimization, which gives rise to a breakup limit. We demonstrated in this work that the breakup limit can be overpassed drastically by using electric current to interfere. Electric current free energy is dependent on the microstructure configuration. The breakup causes the electric current free energy to reduce in some cases. This compensates the increment of interfacial free energy during breaking up and enables the processing to achieve finer microstructure. With engineering practical electric current parameters, our calculation revealed a significant increment of the obtainable number of particles, showing electric current a powerful microstructure refinement technology. The calculation is validated by our experiments on the breakup of Fe3C-plates in Fe matrix. Furthermore, there is a parameter range that electric current can drive spherical particles to split into smaller ones
Mechanics of fragmentation of crocodile skin and other thin films
Fragmentation of thin layers of materials is mediated by a network of cracks on its surface. It is commonly seen in dehydrated paintings or asphalt pavements and even in graphene or other two-dimensional materials, but is also observed in the characteristic polygonal pattern on a crocodile’s head. Here, we build a simple mechanical model of a thin film and investigate the generation and development of fragmentation patterns as the material is exposed to various modes of deformation. We find that the characteristic size of fragmentation, defined by the mean diameter of polygons, is strictly governed by mechanical properties of the film material. Our result demonstrates that skin fragmentation on the head of crocodiles is dominated by that it features a small ratio between the fracture energy and Young’s modulus, and the patterns agree well with experimental observations. Understanding this mechanics-driven process could be applied to improve the lifetime and reliability of thin film coatings by mimicking crocodile skin
Perturbation with Intrabodies Reveals That Calpain Cleavage Is Required for Degradation of Huntingtin Exon 1
Background:
Proteolytic processing of mutant huntingtin (mHtt), the protein that causes Huntington's disease (HD), is critical for mHtt toxicity and disease progression. mHtt contains several caspase and calpain cleavage sites that generate N-terminal fragments that are more toxic than full-length mHtt. Further processing is then required for the degradation of these fragments, which in turn, reduces toxicity. This unknown, secondary degradative process represents a promising therapeutic target for HD.
Methodology/Principal Findings: We have used intrabodies, intracellularly expressed antibody fragments, to gain insight into the mechanism of mutant huntingtin exon 1 (mHDx-1) clearance. Happ1, an intrabody recognizing the proline-rich region of mHDx-1, reduces the level of soluble mHDx-1 by increasing clearance. While proteasome and macroautophagy inhibitors reduce turnover of mHDx-1, Happ1 is still able to reduce mHDx-1 under these conditions, indicating Happ1-accelerated mHDx-1 clearance does not rely on these processes. In contrast, a calpain inhibitor or an inhibitor of lysosomal pH block Happ1-mediated acceleration of mHDx-1 clearance. These results suggest that mHDx-1 is cleaved by calpain, likely followed by lysosomal degradation and this process regulates the turnover rate of mHDx-1. Sequence analysis identifies amino acid (AA) 15 as a potential calpain cleavage site. Calpain cleavage of recombinant mHDx-1 in vitro yields fragments of sizes corresponding to this prediction. Moreover, when the site is blocked by binding of another intrabody, V_L12.3, turnover of soluble mHDx-1 in living cells is blocked.
Conclusions/Significance:
These results indicate that calpain-mediated removal of the 15 N-terminal AAs is required for the degradation of mHDx-1, a finding that may have therapeutic implications
Accounting Problems Under the Excess Profits Tax
DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p
NADPH oxidase and reactive oxygen species contribute to alcohol-induced microglial activation and neurodegeneration
<p>Abstract</p> <p>Background</p> <p>Activation of microglia causes the production of proinflammatory factors and upregulation of NADPH oxidase (NOX) that form reactive oxygen species (ROS) that lead to neurodegeneration. Previously, we reported that 10 daily doses of ethanol treatment induced innate immune genes in brain. In the present study, we investigate the effects of chronic ethanol on activation of NOX and release of ROS, and their contribution to ethanol neurotoxicity.</p> <p>Methods</p> <p>Male C57BL/6 and NF-κB enhanced GFP mice were treated intragastrically with water or ethanol (5 g/kg, i.g., 25% ethanol w/v) daily for 10 days. The effects of chronic ethanol on cell death markers (activated caspase-3 and Fluoro-Jade B), microglial morphology, NOX, ROS and NF-κB were examined using real-time PCR, immunohistochemistry and hydroethidine histochemistry. Also, Fluoro-Jade B staining and NOX gp91<sup>phox </sup>immunohistochemistry were performed in the orbitofrontal cortex (OFC) of human postmortem alcoholic brain and human moderate drinking control brain.</p> <p>Results</p> <p>Ethanol treatment of C57BL/6 mice showed increased markers of neuronal death: activated caspase-3 and Fluoro-Jade B positive staining with Neu-N (a neuronal marker) labeling in cortex and dentate gyrus. The OFC of human post-mortem alcoholic brain also showed significantly more Fluoro-Jade B positive cells colocalized with Neu-N, a neuronal marker, compared to the OFC of human moderate drinking control brain, suggesting increased neuronal death in the OFC of human alcoholic brain. Iba1 and GFAP immunohistochemistry showed activated morphology of microglia and astrocytes in ethanol-treated mouse brain. Ethanol treatment increased NF-κB transcription and increased NOX gp91<sup>phox </sup>at 24 hr after the last ethanol treatment that remained elevated at 1 week. The OFC of human postmortem alcoholic brain also had significant increases in the number of gp91<sup>phox </sup>+ immunoreactive (IR) cells that are colocalized with neuronal, microglial and astrocyte markers. In mouse brain ethanol increased gp91<sup>phox </sup>expression coincided with increased production of O<sub>2</sub><sup>- </sup>and O<sub>2</sub><sup>- </sup>- derived oxidants. Diphenyleneiodonium (DPI), a NOX inhibitor, reduced markers of neurodegeneration, ROS and microglial activation.</p> <p>Conclusions</p> <p>Ethanol activation of microglia and astrocytes, induction of NOX and production of ROS contribute to chronic ethanol-induced neurotoxicity. NOX-ROS and NF-κB signaling pathways play important roles in chronic ethanol-induced neuroinflammation and neurodegeneration.</p
Algorithms for locating extremely conserved elements in multiple sequence alignments
<p>Abstract</p> <p>Background</p> <p>In 2004, Bejerano <it>et al</it>. announced the startling discovery of hundreds of "ultraconserved elements", long genomic sequences perfectly conserved across human, mouse, and rat. Their announcement stimulated a flurry of subsequent research.</p> <p>Results</p> <p>We generalize the notion of ultraconserved element in a natural way from extraordinary human-rodent conservation to extraordinary conservation over an arbitrary set of species. We call these "Extremely Conserved Elements". There is a linear time algorithm to find all such Extremely Conserved Elements in any multiple sequence alignment, provided that the conservation is required to be across all the aligned species. For the general case of conservation across an arbitrary subset of the aligned species, we show that the question of whether there exists an Extremely Conserved Element is <it>NP</it>-complete. We illustrate the linear time algorithm by cataloguing all 177 Extremely Conserved Elements in the currently available 44-vertebrate whole-genome alignment, and point out some of the characteristics of these elements.</p> <p>Conclusions</p> <p>The <it>NP</it>-completeness in the case of conservation across an arbitrary subset of the aligned species implies that it is unlikely an efficient algorithm exists for this general case. Despite this fact, for the interesting case of conservation across all or most of the aligned species, our algorithm is efficient enough to be practical. The 177 Extremely Conserved Elements that we catalog demonstrate many of the characteristics of the original ultraconserved elements of Bejerano <it>et al</it>.</p
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