The Energy-absorbing Characteristics of Novel Contoured Core Sandwich Structures

Automobile and aerospace industries are facing problems more and more on reducing the weight and manufacturing cost of a structure, but guaranteeing an equal level of comfort with satisfactory structural performance of components. To overcome these contradictory requirements traditional designs and materials must be revised. Therefore, this research study aims to design, manufacture and characterise the properties of novel contoured-core sandwich structures to obtain strong, stiff and lightweight structures including air ventilation to reduce the danger of deterioration and humidity retraction. Two different contoured profiles, named flat-roof and spherical-roof contoured-cores, were designed to investigate structural response under quasi-static and dynamic loading conditions. Flat-roof and spherical-roof structures were made from a glass fibre reinforced plastic (GFRP) and a carbon fibre reinforced plastic (CFRP). The composite contoured cores were fabricated using a hot press moulding technique and then bonded to skins based on the same material, to produce a range of lightweight sandwich structures. Testing was initially focused on establishing the influence of the number of unit cells, thickness of the cell wall, width of the cell and the core filled with foam on their mechanical behaviour under quasi-static loading. Fibre fracture and matrix cracking in the composite systems, as well as debonding between the skins and the core, were observed during the compression. The compression strength and modulus were shown to be dependent on the number of unit cells and the cell wall thickness. It has also been shown that the specific energy absorption capacity of the panel increases nonlinearly with increasing the cell wall thickness, with the spherical-roof cores outperforming their flat-roof counterparts. Moreover, the foam filling on the composite contoured-core systems improved the strength as well as specific energy-absorbing characteristics of the structures. Low velocity impact loading was subsequently performed on the sandwich structures and showed that the values of energy absorption were slightly higher than the tests conducted at quasi-static loading, as a result of the rate-sensitive effects on the damage resistance of the composite material. In addition, blast tests were undertaken to subject the core materials to a much higher strain-rate. Extensive crushing of the contoured cores was observed, suggesting that these structures are capable of absorbing a significant amount of energy under the extreme loading condition. Finally, the results of these tests were compared with previously-published data on a range of similar core structures. The energy absorbing characteristics of the current spherical-roof systems are shown to be superior to other core structures, such as aluminium and composite egg-box structures. The finite element models using ABAQUS/explicit were further developed to simulate the quasi-static and low velocity impact response of woven carbon and glass fibre contoured-core designs. Initially, a two dimensional model with Hashin’s failure criteria was developed to compare with the experiment. Following this, a user defined material subroutine (VUMAT) was implemented to model the through thickness damage of the contoured-core structures using Hashin’s 3D failure criteria. The FE models were validated against the experimental results in terms of the stress-strain responses, the specific energy absorption and the failure mode, with reasonably good correlation. The models developed could be further used for parametric studies to assist in designing and optimising the structural behaviour of contoured-core sandwich structures

P. falciparum Modulates Erythroblast Cell Gene Expression in Signaling and Erythrocyte Production Pathways

Global, genomic responses of erythrocytes to infectious agents have been difficult to measure because these cells are e-nucleated. We have previously demonstrated that in vitro matured, nucleated erythroblast cells at the orthochromatic stage can be efficiently infected by the human malaria parasite Plasmodium falciparum. We now show that infection of orthochromatic cells induces change in 609 host genes. 592 of these transcripts are up-regulated and associated with metabolic and chaperone pathways unique to P. falciparum infection, as well as a wide range of signaling pathways that are also induced in related apicomplexan infections of mouse hepatocytes or human fibroblast cells. Our data additionally show that polychromatophilic cells, which precede the orthochromatic stage and are not infected when co-cultured with P. falciparum, up-regulate a small set of genes, at least two of which are associated with pathways of hematopoiesis and/or erythroid cell development. These data support the idea that P. falciparum affects erythropoiesis at multiple stages during erythroblast differentiation. Further P. falciparum may modulate gene expression in bystander erythroblasts and thus influence pathways of erythrocyte development. This study provides a benchmark of the host erythroblast cell response to infection by P. falciparum

Zanamivir Conjugated to Poly-L-Glutamine is Much More Active Against Influenza Viruses in Mice and Ferrets Than the Drug Itself

Purpose: Previously, polymer-attached zanamivir had been found to inhibit influenza A viruses in vitro far better than did small-molecule zanamivir (1) itself. The aim of this study was to identify in vitro—using the plaque reduction assay—a highly potent 1-polymer conjugate, and subsequently test its antiviral efficacy in vivo. Methods: By examining the structure-activity relationship of 1-polymer conjugates in the plaque assay, we have determined that the most potent inhibitor against several representative influenza virus strains has a neutral high-molecular-weight backbone and a short alkyl linker. We have examined this optimal polymeric inhibitor for efficacy and immunogenicity in the mouse and ferret models of infection. Results: 1 attached to poly-L-glutamine is an effective therapeutic for established influenza infection in ferrets, reducing viral titers up to 30-fold for 6 days. There is also up to a 190-fold reduction in viral load when the drug is used as a combined prophylactic/therapeutic in mice. Additionally, we see no evidence that the drug conjugate stimulates an immune response in mice upon repeat administration. Conclusions: 1 attached to a neutral high-molecular-weight backbone through a short alkyl linker drastically reduced both in vitro and in vivo titers compared to those observed with 1 itself. Thus, further development of this polymeric zanamivir for the mitigation of influenza infection seems warranted.National Institutes of Health (U.S.) (Grant U01-AI074443

Shakedown Limits of Slab Track Substructures and Their Implications for Design

This paper presents an approach to shakedown of slab track substructures subjected to train loads. The train load is converted into a distributed moving load on the substructure surface using a simplified track analysis. Based on the lower-bound dynamic shakedown theorem, shakedown solutions for the slab track substructures are obtained over a range of train speeds between zero and the critical speed of the track. It is found the shakedown limit is largely influenced by the ratio of layer elastic moduli and the ratio of train speed to critical speed rather than their absolute values. An attenuation factor, as a function of the critical speed and the friction angle of subsoil, is proposed to effectively obtain the shakedown limit of the slab track substructure at any train speed. In light of the shakedown solutions, improvements to the existing design and analysis approaches are also suggested

Loss of the interferon-γ-inducible regulatory immunity-related GTPase (IRG), Irgm1, causes activation of effector IRG proteins on lysosomes, damaging lysosomal function and predicting the dramatic susceptibility of Irgm1-deficient mice to infection

The interferon-γ (IFN-γ)-inducible immunity-related GTPase (IRG), Irgm1, plays an essential role in restraining activation of the IRG pathogen resistance system. However, the loss of Irgm1 in mice also causes a dramatic but unexplained susceptibility phenotype upon infection with a variety of pathogens, including many not normally controlled by the IRG system. This phenotype is associated with lymphopenia, hemopoietic collapse, and death of the mouse.Deutscher Akademischer Austausch Dienst (DAAD); International Graduate School in Development Health and Disease (IGS-DHD); Deutsche For-schungsgemeinschaft (SFBs 635, 670, 680); Max-Planck-Gesellschaft (Max Planck Fellowship)

Antimonial Resistance in Leishmania donovani Is Associated with Increased In Vivo Parasite Burden

Leishmania donovani is an intracellular protozoan parasite that causes visceral leishmaniasis (VL). Antimonials (SSG) have long been the first-line treatment against VL, but have now been replaced by miltefosine (MIL) in the Indian subcontinent due to the emergence of SSG-resistance. Our previous study hypothesised that SSG-resistant L. donovani might have increased in vivo survival skills which could affect the efficacy of other treatments such as MIL. The present study attempts to validate these hypotheses. Fourteen strains derived from Nepalese clinical isolates with documented SSG-susceptibility were infected in BALB/c mice to study their survival capacity in drug free conditions (non-treated mice) and in MIL-treated mice. SSG-resistant parasites caused a significant higher in vivo parasite load compared to SSG-sensitive parasites. However, this did not seem to affect the strains' response to MIL-treatment since parasites from both phenotypes responded equally well to in vivo MIL exposure. We conclude that there is a positive association between SSG-resistance and in vivo survival skills in our sample of L. donovani strains which could suggest a higher virulence of SSG-R strains compared to SSG-S strains. These greater in vivo survival skills of SSG-R parasites do not seem to directly affect their susceptibility to MIL. However, it cannot be excluded that repeated MIL exposure will elicit different adaptations in these SSG-R parasites with superior survival skills compared to the SSG-S parasites. Our results therefore highlight the need to closely monitor drug efficacy in the field, especially in the context of the Kala-azar elimination programme ongoing in the Indian subcontinent

Immunophenotyping of Circulating T Helper Cells Argues for Multiple Functions and Plasticity of T Cells In Vivo in Humans - Possible Role in Asthma

BACKGROUND: The immune process driving eosinophilic and non-eosinophilic asthma is likely driven by different subsets of T helper (Th) cells. Recently, in vitro studies and animal studies suggest that Th cell subsets displays plasticity by changing their transcription factor or by expressing multiple transcription factors. Our aim was to determine whether individuals with asthma and elevated circulating eosinophils express signs of different regulatory immune mechanisms compared with asthmatics with low blood eosinophils and non-asthmatic control subjects. In addition, determine the relationship between eosinophilia and circulating Th cell subsets. METHODOLOGY/PRINCIPAL FINDINGS: Participants were selected from a random epidemiological cohort, the West Sweden Asthma Study. Immunophenotypes of fresh peripheral blood cells obtained from stable asthmatics, with and without elevated eosinophilic inflammation (EOS high and EOS low respectively) and control subjects, were determined by flow cytometry. No differences in the number of Th1 (T-bet), Th2 (GATA-3), Th17 (RORγt) or Treg (FOXP3) cells were observed between the groups when analysing each subset separately. However, in all groups, each of the Th subsets showed expression of additional canonical transcription factors T-bet, GATA-3, RORγt and FOXP3. Furthermore, by in vitro stimulation with anti-CD3/anti-CD28 there was a significant increase of single expressing GATA-3(+) and co-expressing T-bet(+)GATA-3(+) cells in the EOS high asthmatics in comparison with control subjects. In addition, T-bet(-)GATA-3(+)RORγt(+)FOXP3(+) were decreased in comparison to the EOS low asthmatics. Finally, in a group of control subjects we found that the majority of proliferating Th cells (CD4(+)CD25(+)Ki67(+)) expressed three or four transcription factors. CONCLUSIONS: The ability of human Th cells to express several regulatory transcription factors suggests that these cells may display plasticity in vivo