Settlement Analysis of Circular Footings on Layered Soil Systems

Many studies are available on the settlement analysis of footings on a homogeneous soil deposit underlain by a rigid base. However, the soil profile is seldom homogenous and typically a layered soil system is encountered in practice. The present study deals with the settlement profiles of soil underneath a circular footing of radius equal to a, and resting on a finite two-layered soil system with thicknesses equal to H1 and H2. The deformation moduli and Poisson’s ratios of the two layers are E1, υ1, and E2, υ2. The settlement profiles are proposed for varying H1/a and H2/a ratios (H1/a= 0.2, 0.5, 1, 2, 4 and 6, and H2/a= 1, 2, 4 and 6). The moduli ratio E1/E2is varied as 0.01, 0.05, 0.1, 0.5, 1, 2, 5 and 20. The extent of settlement due to load is also proposed from the surface settlement profile which can help in determining the influence of a footing on the neighboring footing or structure. The analysis is carried out using PLAXIS 2D vAE. In addition, the settlement influence factors are proposed for the above mentioned ratios to estimate the maximum settlement of the footing on a layered system. The results are also compared with the settlement measured in a building on a layered system in Adelaide, Southern Australia, and the results are found to be comparable

Analysis of Metallised Propellant Ignition Process under Conductive Heating

Ignition of a composite aluminised propellant (AP-HTPB-Al) in stagnant hot air is analysed theoretically, based on solid phase and gas phase theories. According to solid phase theory, ignition is due to reaction of the propellant in the solid phase at elevated temperatures. One-dimensional transient solid phase energy equation is solved to obtain the surface temperature profile of the propellant. By gas phase theory, an exothermic gas phase reaction, adjacent to the propellant surface, is considered responsible for the ignition. The changes in temperature and concentrations in the gas phase and the temperature profile below the propellant surface during the pre-ignition induction period are considered. Equations of energy and concentrations of reactants have been solved to obtain the species concentration and temperature profiles in the gas phase. An experimental investigation of the ignition of AP-HTPB-Al propellant is also carried out in a shock tube under end-mount conditions. Pressure and temperature ranges were 6-16 bar and 1500-3000 K, respectively. A comparison of the experimental data with predicted results shows that the ignition in an oxidizing atmosphere is by gas phase reaction, whereas in an inert atmosphere, solid phase reaction may be predominant

National culture and tourist destination choice in the UK and Venezuela: an exploratory and preliminary study

National culture determines consumer attitudes and behaviour. While this holds true for tourism consumption, little research has sought to better understand the effect of culture on tourist destination choice. The geographical scope of analysis has also been restricted. This study employs the Hofstede’s cultural dimensions framework to conduct an exploratory, qualitative evaluation of the influence of the tourist cultural background on destination choice. It focuses on the UK and Venezuela, the two countries with significant cultural differences and forecast growth in outbound tourism. The study shows the distinct role of culture in tourist preferences for destination choice and structure of travel groups. The effect of culture is also recorded in how tourists research destinations prior to visit and perceive travel risks, thus ultimately influencing their motivation to travel. Recommendations are developed on how to integrate knowledge on the cultural background of tourists into tourism management and policy-making practices

In Vitro and In Vivo Studies Identify Important Features of Dengue Virus pr-E Protein Interactions

Flaviviruses bud into the endoplasmic reticulum and are transported through the secretory pathway, where the mildly acidic environment triggers particle rearrangement and allows furin processing of the prM protein to pr and M. The peripheral pr peptide remains bound to virus at low pH and inhibits virus-membrane interaction. Upon exocytosis, the release of pr at neutral pH completes virus maturation to an infectious particle. Together this evidence suggests that pr may shield the flavivirus fusion protein E from the low pH environment of the exocytic pathway. Here we developed an in vitro system to reconstitute the interaction of dengue virus (DENV) pr with soluble truncated E proteins. At low pH recombinant pr bound to both monomeric and dimeric forms of E and blocked their membrane insertion. Exogenous pr interacted with mature infectious DENV and specifically inhibited virus fusion and infection. Alanine substitution of E H244, a highly conserved histidine residue in the pr-E interface, blocked pr-E interaction and reduced release of DENV virus-like particles. Folding, membrane insertion and trimerization of the H244A mutant E protein were preserved, and particle release could be partially rescued by neutralization of the low pH of the secretory pathway. Thus, pr acts to silence flavivirus fusion activity during virus secretion, and this function can be separated from the chaperone activity of prM. The sequence conservation of key residues involved in the flavivirus pr-E interaction suggests that this protein-protein interface may be a useful target for broad-spectrum inhibitors

A DNA Sequence Directed Mutual Transcription Regulation of HSF1 and NFIX Involves Novel Heat Sensitive Protein Interactions

BACKGROUND: Though the Nuclear factor 1 family member NFIX has been strongly implicated in PDGFB-induced glioblastoma, its molecular mechanisms of action remain unknown. HSF1, a heat shock-related transcription factor is also a powerful modifier of carcinogenesis by several factors, including PDGFB. How HSF1 transcription is controlled has remained largely elusive. METHODOLOGY/PRINCIPAL FINDINGS: By combining microarray expression profiling and a yeast-two-hybrid screen, we identified that NFIX and its interactions with CGGBP1 and HMGN1 regulate expression of HSF1. We found that CGGBP1 organizes a bifunctional transcriptional complex at small CGG repeats in the HSF1 promoter. Under chronic heat shock, NFIX uses CGGBP1 and HMGN1 to get recruited to this promoter and in turn affects their binding to DNA. Results show that the interactions of NFIX with CGGBP1 and HMGN1 in the soluble fraction are heat shock sensitive due to preferential localization of CGGBP1 to heterochromatin after heat shock. HSF1 in turn was found to bind to the NFIX promoter and repress its expression in a heat shock sensitive manner. CONCLUSIONS/SIGNIFICANCE: NFIX and HSF1 exert a mutual transcriptional repressive effect on each other which requires CGG repeat in HSF1 promoter and HSF1 binding site in NFIX promoter. We unravel a unique mechanism of heat shock sensitive DNA sequence-directed reciprocal transcriptional regulation between NFIX and HSF1. Our findings provide new insights into mechanisms of transcription regulation under stress

Receptor Complementation and Mutagenesis Reveal SR-BI as an Essential HCV Entry Factor and Functionally Imply Its Intra- and Extra-Cellular Domains

HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI), a major receptor of high-density lipoprotein (HDL), the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection

Shape coexistence in the neutron-deficient lead region: A systematic study of lifetimes in the even-even 188−200^{188-200}Hg with GRIFFIN

Lifetimes of $2^+_1$ and $4^+_1$ states, as well as some negative-parity and non-yrast states, in $^{188-200}$Hg were measured using $\gamma-\gamma$ electronic fast timing techniques with the LaBr$_3$(Ce) detector array of the GRIFFIN spectrometer. The excited states were populated in the $\epsilon/\beta^+$-decay of $J^\pi =7^+/2^-$ $^{188-200}$Tl produced at the TRIUMF-ISAC facility. The deduced B(E2) values are compared to different interacting boson model predictions. The precision achieved in this work over previous ones allows for a meaningful comparison with the different theoretical models of these transitional Hg isotopes, which confirms the onset of state mixing in $^{190}$Hg

Human cytomegalovirus immediate-early 1 protein rewires upstream STAT3 to downstream STAT1 signaling switching an IL6-type to an IFNγ-like response

MN and CP were supported by the Wellcome Trust (www.wellcome.ac.uk) Institutional Strategic Support Fund and CP was supported by the Deutsche Forschungsgemeinschaft (PA 815/2-1; www.dfg.de).The human cytomegalovirus (hCMV) major immediate-early 1 protein (IE1) is best known for activating transcription to facilitate viral replication. Here we present transcriptome data indicating that IE1 is as significant a repressor as it is an activator of host gene expression. Human cells induced to express IE1 exhibit global repression of IL6- and oncostatin M-responsive STAT3 target genes. This repression is followed by STAT1 phosphorylation and activation of STAT1 target genes normally induced by IFNγ. The observed repression and subsequent activation are both mediated through the same region (amino acids 410 to 445) in the C-terminal domain of IE1, and this region serves as a binding site for STAT3. Depletion of STAT3 phenocopies the STAT1-dependent IFNγ-like response to IE1. In contrast, depletion of the IL6 receptor (IL6ST) or the STAT kinase JAK1 prevents this response. Accordingly, treatment with IL6 leads to prolonged STAT1 instead of STAT3 activation in wild-type IE1 expressing cells, but not in cells expressing a mutant protein (IE1dl410-420) deficient for STAT3 binding. A very similar STAT1-directed response to IL6 is also present in cells infected with a wild-type or revertant hCMV, but not an IE1dl410-420 mutant virus, and this response results in restricted viral replication. We conclude that IE1 is sufficient and necessary to rewire upstream IL6-type to downstream IFNγ-like signaling, two pathways linked to opposing actions, resulting in repressed STAT3- and activated STAT1-responsive genes. These findings relate transcriptional repressor and activator functions of IE1 and suggest unexpected outcomes relevant to viral pathogenesis in response to cytokines or growth factors that signal through the IL6ST-JAK1-STAT3 axis in hCMV-infected cells. Our results also reveal that IE1, a protein considered to be a key activator of the hCMV productive cycle, has an unanticipated role in tempering viral replication.Publisher PDFPeer reviewe