Brane World Cosmology Without the Z_2 Symmetry

The Friedmann equation for a positive tension brane situated between two bulk spacetimes that posses the same 5D cosmological constant, but which does not posses a Z2 symmetry of the metric itself is derived, and the possible effects of dropping the Z2 symmetry on the expansion of our Universe are examined; cosmological constraints are discussed. We show the effect of this is an inflation-like period at very early times. The global solutions for the metric in the infinite extra dimension case are found and comparison with the symmetric case is made. We show that any brane world senario of this type must revert to a Z2 symmetric form at late times, and hence rule out certain proposed scenarios

Adjusted Estimates of Worker Flows and Job Openings in JOLTS

We develop and implement a method to improve estimates of worker flows and job openings based on the Job Openings and Labor Turnover Survey (JOLTS). Our method involves reweighting the cross-sectional density of employment growth rates in JOLTS to match the corresponding density in the comprehensive Business Employment Dynamics (BED) data. To motivate our work, we compare JOLTS to other data sources and document large discrepancies with respect to aggregate employment growth, the magnitude of worker flows, and the cross-sectional density of establishment growth rates. We also discuss issues related to JOLTS sample design and nonresponse corrections. Our adjusted statistics for hires and separations exceed the published statistics by about one-third. The adjusted layoff rate is more than 60 percent greater than the published layoff rate. Time-series properties are also affected. For example, hires exhibit more volatility than separations in the published statistics, but the reverse holds in the adjusted statistics. The impact of our adjustment methodology on estimated job openings is more modest, raising the vacancy rate by about 8 percent.

Methods of enhancing the sustainability and scale of community based disaster risk management

Disasters are always local in their impact, and therefore approaches towards their alleviation need to be designed and implemented based on this certainty. So this research is designed to investigate methods of enhancing the development, sustainability and scale of community based disaster risk management (CBDRM). This is undertaken with a special focus upon community risk assessment (CRA) and its relationship with disaster risk reduction (DRR). Action Research (AR) is the methodological approach adopted to investigate three primary research objectives: • To investigate the link between community risk assessment (CRA) and community based disaster risk management (CBDRM). • To identify key issues when addressing the underlying causes of vulnerability within community based disaster risk management (CBDRM). • To identify challenges in enhancing the sustainability and scale of community based disaster risk management (CBDRM) through stakeholder partnership. The AR carried out has three main components: 1. The development and testing of a CRA methodology. 2. The identification of good practice CBDRM. 3. Supplementary semi-structured interviews. Perspectives on the research objectives are collated from a broad array of international experiences, but with the primary location of fieldwork in Bihar, India. Conclusions to the research demonstrate the importance of linking government policy and practice on DRR with CBDRM, and addressing the underlying causes of vulnerability. While important in their own right, these subjects have also been considered in terms of their inter-connectedness with one another. Indeed they are shown to be mutually reinforcing. However, even more pivotal is the emphasis on their relationship with CRA. Furthermore, contrary to much practice CRA, engaging government officials from the outset and incorporating an investigation into the underlying causes of vulnerability, must not be segregated from action planning but must be fully synchronised with a CBDRM process.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Expression and Comparative Genomics of Two Serum Response Factor Genes in Zebrafish

Serum response factor (SRF) is a single copy, highly conserved transcription factor that governs the expression of hundreds of genes involved with actin cytoskeletal organization, cellular growth and signaling, neuronal circuitry and muscle differentiation. Zebrafish have emerged as a facile and inexpensive vertebrate model to delineate gene expression, regulation, and function, and yet the study of SRF in this animal has been virtually unexplored. Here, we report the existence of two srf genes in zebrafish, with partially overlapping patterns of expression in 3 and 7 day old developing animals. The mammalian ortholog (srf1) encodes for a 520 amino acid protein expressed in adult vascular and visceral smooth muscle cells, cardiac and skeletal muscle, as well as neuronal cells. The second zebrafish srf gene (srf2), encoding for a presumptive protein of only 314 amino acids, is transcribed at lower levels and appears to be less widely expressed across adult tissues. Both srf genes are induced by the SRF coactivator myocardin and attenuated with a short hairpin RNA to mammalian SRF. Promoter studies with srf1 reveal conserved CArG boxes that are the targets of SRF-myocardin in embryonic zebrafish cells. These results reveal that SRF was duplicated in the zebrafish genome and that its protein expression in all three muscle cell types is highly conserved across vertebrate animals suggesting an ancient code for transcriptional regulation of genes unique to muscle cell lineages

Evidence for a colour dependence in the size distribution of main belt asteroids

We present the results of a project to detect small (~1 km) main-belt asteroids with the 3.6 meter Canada-France-Hawaii Telescope (CFHT). We observed in 2 filters (MegaPrime g' and r') in order to compare the results in each band. Owing to the observational cadence we did not observe the same asteroids through each filter and thus do not have true colour information. However strong differences in the size distributions as seen in the two filters point to a colour-dependence at these sizes, perhaps to be expected in this regime where asteroid cohesiveness begins to be dominated by physical strength and composition rather than by gravity. The best fit slopes of the cumulative size distributions (CSDs) in both filters tend towards lower values for smaller asteroids, consistent with the results of previous studies. In addition to this trend, the size distributions seen in the two filters are distinctly different, with steeper slopes in r' than in g'. Breaking our sample up according to semimajor axis, the difference between the filters in the inner belt is found to be somewhat less pronounced than in the middle and outer belt, but the CSD of those asteroids seen in the r' filter is consistently and significantly steeper than in g' throughout. The CSD slopes also show variations with semimajor axis within a given filter, particularly in r'. We conclude that the size distribution of main belt asteroids is likely to be colour dependent at kilometer sizes and that this dependence may vary across the belt.Comment: 28 pages, 5 figures, submitted to the Astronomical Journa

Amyloid beta dimers/trimers potently induce cofilin-actin rods that are inhibited by maintaining cofilin-phosphorylation

<p>Abstract</p> <p>Background</p> <p>Previously we reported 1 μM synthetic human amyloid beta_1-42oligomers induced cofilin dephosphorylation (activation) and formation of cofilin-actin rods within rat hippocampal neurons primarily localized to the dentate gyrus.</p> <p>Results</p> <p>Here we demonstrate that a gel filtration fraction of 7PA2 cell-secreted SDS-stable human Aβ dimers and trimers (Aβd/t) induces maximal neuronal rod response at ~250 pM. This is 4,000-fold more active than traditionally prepared human Aβ oligomers, which contain SDS-stable trimers and tetramers, but are devoid of dimers. When incubated under tyrosine oxidizing conditions, synthetic human but not rodent Aβ_1-42, the latter lacking tyrosine, acquires a marked increase (620 fold for EC₅₀) in rod-inducing activity. Gel filtration of this preparation yielded two fractions containing SDS-stable dimers, trimers and tetramers. One, eluting at a similar volume to 7PA2 Aβd/t, had maximum activity at ~5 nM, whereas the other, eluting at the void volume (high-n state), lacked rod inducing activity at the same concentration. Fractions from 7PA2 medium containing Aβ monomers are not active, suggesting oxidized SDS-stable Aβ_1-42dimers in a low-n state are the most active rod-inducing species. Aβd/t-induced rods are predominantly localized to the dentate gyrus and mossy fiber tract, reach significance over controls within 2 h of treatment, and are reversible, disappearing by 24 h after Aβd/t washout. Overexpression of cofilin phosphatases increase rod formation when expressed alone and exacerbate rod formation when coupled with Aβd/t, whereas overexpression of a cofilin kinase inhibits Aβd/t-induced rod formation.</p> <p>Conclusions</p> <p>Together these data support a mechanism by which Aβd/t alters the actin cytoskeleton via effects on cofilin in neurons critical to learning and memory.</p

A novel HLA-B18 restricted CD8+ T cell epitope is efficiently cross-presented by dendritic cells from soluble tumor antigen

NY-ESO-1 has been a major target of many immunotherapy trials because it is expressed by various cancers and is highly immunogenic. In this study, we have identified a novel HLA-B*1801-restricted CD8&lt;sup&gt;+&lt;/sup&gt;T cell epitope, NY-ESO-1&lt;sub&gt;88–96&lt;/sub&gt; (LEFYLAMPF) and compared its direct- and cross-presentation to that of the reported NY-ESO-1&lt;sub&gt;157–165&lt;/sub&gt; epitope restricted to HLA-A*0201. Although both epitopes were readily cross-presented by DCs exposed to various forms of full-length NY-ESO-1 antigen, remarkably NY-ESO-1&lt;sub&gt;88–96&lt;/sub&gt; is much more efficiently cross-presented from the soluble form, than NY-ESO-1&lt;sub&gt;157–165&lt;/sub&gt;. On the other hand, NY-ESO-1&lt;sub&gt;157–165&lt;/sub&gt; is efficiently presented by NY-ESO-1-expressing tumor cells and its presentation was not enhanced by IFN-γ treatment, which induced immunoproteasome as demonstrated by Western blots and functionally a decreased presentation of Melan A&lt;sub&gt;26–35&lt;/sub&gt;; whereas NY-ESO-1&lt;sub&gt;88–96&lt;/sub&gt; was very inefficiently presented by the same tumor cell lines, except for one that expressed high level of immunoproteasome. It was only presented when the tumor cells were first IFN-γ treated, followed by infection with recombinant vaccinia virus encoding NY-ESO-1, which dramatically increased NY-ESO-1 expression. These data indicate that the presentation of NY-ESO-1&lt;sub&gt;88–96&lt;/sub&gt; is immunoproteasome dependent. Furthermore, a survey was conducted on multiple samples collected from HLA-B18+ melanoma patients. Surprisingly, all the detectable responses to NY-ESO-1&lt;sub&gt;88–96&lt;/sub&gt; from patients, including those who received NY-ESO-1 ISCOMATRIX™ vaccine were induced spontaneously. Taken together, these results imply that some epitopes can be inefficiently presented by tumor cells although the corresponding CD8&lt;sup&gt;+&lt;/sup&gt;T cell responses are efficiently primed in vivo by DCs cross-presenting these epitopes. The potential implications for cancer vaccine strategies are further discussed

KinImmerse: Macromolecular VR for NMR ensembles

<p>Abstract</p> <p>Background</p> <p>In molecular applications, virtual reality (VR) and immersive virtual environments have generally been used and valued for the visual and interactive experience – to enhance intuition and communicate excitement – rather than as part of the actual research process. In contrast, this work develops a software infrastructure for research use and illustrates such use on a specific case.</p> <p>Methods</p> <p>The Syzygy open-source toolkit for VR software was used to write the KinImmerse program, which translates the molecular capabilities of the kinemage graphics format into software for display and manipulation in the DiVE (Duke immersive Virtual Environment) or other VR system. KinImmerse is supported by the flexible display construction and editing features in the KiNG kinemage viewer and it implements new forms of user interaction in the DiVE.</p> <p>Results</p> <p>In addition to molecular visualizations and navigation, KinImmerse provides a set of research tools for manipulation, identification, co-centering of multiple models, free-form 3D annotation, and output of results. The molecular research test case analyzes the local neighborhood around an individual atom within an ensemble of nuclear magnetic resonance (NMR) models, enabling immersive visual comparison of the local conformation with the local NMR experimental data, including target curves for residual dipolar couplings (RDCs).</p> <p>Conclusion</p> <p>The promise of KinImmerse for production-level molecular research in the DiVE is shown by the locally co-centered RDC visualization developed there, which gave new insights now being pursued in wider data analysis.</p