Application of CFD to sonic boom near and mid flow-field prediction

A 3-D parabolized Navier-Stokes (PNS) code was used to calculate the supersonic overpressures from three different geometries at near- and mid-flow fields. Wind tunnel data is used for code validation. Comparison of the computed results with different grid refinements is shown. It is observed that a large number of grid points is needed to resolve the tail shock/expansion fan interaction. Therefore, an adaptive grid approach is employed to calculate the flow field. The agreement between the numerical results and the wind tunnel data confirms that computational fluid dynamics can be applied to the problem of sonic boom prediction

Cenozoic evolution of the eastern Black Sea: a test of depth-dependent stretching models

Subsidence analysis of the eastern Black Sea basin suggests that the stratigraphy of this deep, extensional basin can be explained by a predominantly pure-shear stretching history. A strain-rate inversion method that assumes pure-shear extension obtains good fits between observed and predicted stratigraphy. A relatively pure-shear strain distribution is also obtained when a strain-rate inversion algorithm is applied that allows extension to vary with depth without assuming its existence or form. The timing of opening of the eastern Black Sea, which occupied a back-arc position during the closure of the Tethys Ocean, has also been a subject of intense debate; competing theories called for basin opening during the Jurassic, Cretaceous or Paleocene/Eocene. Our work suggests that extension likely continued into the early Cenozoic, in agreement with stratigraphic relationships onshore and with estimates for the timing of arc magmatism. Further basin deepening also appears to have occurred in the last 20 myr. This anomalous subsidence event is focused in the northern part of the basin and reaches its peak at 15–10 Ma. We suggest that this comparatively localized shortening is associated with the northward movement of the Arabian plate. We also explore the effects of paleowater depth and elastic thickness on the results. These parameters are controversial, particularly for deep-water basins and margins, but their estimation is a necessary step in any analysis of the tectonic subsidence record stored in stratigraphy. <br/

Photometric and proper motion study of neglected open cluster NGC 2215

Optical UBVRI photometric measurements using the Faulkes Telescope North were taken in early 2011 and combined with 2MASS JHK$_s$ and WISE infrared photometry as well as UCAC4 proper motion data in order to estimate the main parameters of the galactic open cluster NGC 2215 of which large uncertainty exists in the current literature. Fitting a King model we estimate a core radius of 1.12$'\pm$0.04$'$ (0.24$\pm$0.01pc) and a limiting radius of $4.3'\pm$0.5$'$ (0.94$\pm$0.11pc) for the cluster. The results of isochrone fits indicates an age of $log(t)=8.85\pm0.10$ with a distance of $d=790\pm90$pc, a metallicity of $[Fe/H]=-0.40\pm0.10$ dex and a reddening of $E(B-V)=0.26\pm0.04$. A proportion of the work in this study was undertaken by Australian and Canadian upper secondary school students involved in the Space to Grow astronomy education project, and is the first scientific publication to have utilized our star cluster photometry curriculum materials.Comment: 10 pages, 9 Figures, 3 Table

CD4 intragenic SNPs associate with HIV-2 plasma viral load and CD4 count in a community-based study from Guinea-Bissau, West Africa.

OBJECTIVES: The human genetics of HIV-2 infection and disease progression is understudied. Therefore, we studied the effect of variation in 2 genes that encode products critical to HIV pathogenesis and disease progression: CD4 and CD209. DESIGN: This cross-sectional study consisted of 143 HIV-2, 30 HIV-1 + HIV-2 and 29 HIV-1-infected subjects and 194 uninfected controls recruited from rural Guinea-Bissau. METHODS: We genotyped 14 CD4 and 4 CD209 single nucleotide polymorphisms (SNPs) that were tested for association with HIV infection, HIV-2 plasma viral load (high vs. low), and CD4 T-cell count (high vs. low). RESULTS: The most significant association was between a CD4 haplotype rs11575097-rs10849523 and high viral load [odds ratio (OR): = 2.37, 95% confidence interval (CI): 1.35 to 4.19, P = 0.001, corrected for multiple testing], suggesting increased genetic susceptibility to HIV-2 disease progression for individuals carrying the high-risk haplotype. Significant associations were also observed at a CD4 SNP (rs2255301) with HIV-2 infection (OR: = 2.36, 95% CI: 1.19 to 4.65, P = 0.01) and any HIV infection (OR: = 2.50, 95% CI: 1.34 to 4.69, P = 0.004). CONCLUSIONS: Our results support a role of CD4 polymorphisms in HIV-2 infection, in agreement with recent data showing that CD4 gene variants increase risk to HIV-1 in Kenyan female sex workers. These findings indicate at least some commonality in HIV-1 and HIV-2 susceptibility

Random close packing of granular matter

We propose an interpretation of the random close packing of granular materials as a phase transition, and discuss the possibility of experimental verification.Comment: 6 page

Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells.

Candida albicans is the most common cause of hematogenously disseminated and oropharyngeal candidiasis. Both of these diseases are characterized by fungal invasion of host cells. Previously, we have found that C. albicans hyphae invade endothelial cells and oral epithelial cells in vitro by inducing their own endocytosis. Therefore, we set out to identify the fungal surface protein and host cell receptors that mediate this process. We found that the C. albicans Als3 is required for the organism to be endocytosed by human umbilical vein endothelial cells and two different human oral epithelial lines. Affinity purification experiments with wild-type and an als3delta/als3delta mutant strain of C. albicans demonstrated that Als3 was required for C. albicans to bind to multiple host cell surface proteins, including N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. Furthermore, latex beads coated with the recombinant N-terminal portion of Als3 were endocytosed by Chinese hamster ovary cells expressing human N-cadherin or E-cadherin, whereas control beads coated with bovine serum albumin were not. Molecular modeling of the interactions of the N-terminal region of Als3 with the ectodomains of N-cadherin and E-cadherin indicated that the binding parameters of Als3 to either cadherin are similar to those of cadherin-cadherin binding. Therefore, Als3 is a fungal invasin that mimics host cell cadherins and induces endocytosis by binding to N-cadherin on endothelial cells and E-cadherin on oral epithelial cells. These results uncover the first known fungal invasin and provide evidence that C. albicans Als3 is a molecular mimic of human cadherins

Innate Immunity and the Evolution of Resistance to an Emerging Infectious Disease in a Wild Bird

Innate immunity is expected to play a primary role in conferring resistance to novel infectious diseases, but few studies have attempted to examine its role in the evolution of resistance to emerging pathogens in wild vertebrate populations. Here, we used experimental infections and cDNA microarrays to examine whether changes in the innate and/or acquired immune responses likely accompanied the emergence of resistance in house finches (Carpodacus mexicanus) in the eastern United States subject to a recent outbreak of conjunctivitis-causing bacterium (Mycoplasma gallisepticum—MG). Three days following experimental infection with MG, we observed differences in the splenic transcriptional responses between house finches from eastern U.S. populations, with a 12-year history of MG exposure, versus western U.S. populations, with no history of exposure to MG. In particular, western birds down-regulated gene expression, while eastern finches showed no expression change relative to controls. Studies involving poultry have shown that MG can manipulate host immunity, and our observations suggest that pathogen manipulation occurred only in finches from the western populations, outside the range of MG. Fourteen days after infection, eastern finches, but not western finches, up-regulated genes associated with acquired immunity (cell-mediated immunity) relative to controls. These observations suggest population differences in the temporal course of the response to infection with MG and imply that innate immune processes were targets of selection in response to MG in the eastern U.S. population.Organismic and Evolutionary Biolog

An active machine learning discovery platform for membrane-disrupting and pore-forming peptides

Membrane-disrupting and pore-forming peptides (PFPs) play a substantial role in bionanotechnology and can determine the life and death of cells. The control of chemical and ion transport through cell membranes is essential to maintaining concentration gradients. Likewise, the delivery of drugs and intracellular proteins aided by pore-forming agents are of interest in treating malfunctioning cells. Known PFPs tend to be up to 50 residues in length, which is commensurate with the thickness of a lipid bilayer. Accordingly, few short PFPs are known. Here we show that the discovery of PFPs can be accelerated via an active machine learning approach. The approach identified 71 potential PFPs from the 25.6 billion octapeptide sequence space; 13 sequences were tested experimentally, and all were found to have the predicted membrane-disrupting ability, with 1 forming highly stable pores. Experimental verification of the predicted pore-forming ability demonstrated that a range of short peptides can form pores in membranes, while the positioning and characteristics of residues that favour pore-forming behaviour were identified. This approach identified more ultrashort (8-residues, unmodified, non-cyclic) PFPs than previously known. We anticipate our findings and methodology will be useful in discovering new pore-forming and membrane-disrupting peptides for range of applications from nanoreactors to therapeutics

Alternative contingency table measures improve the power and detection of multifactor dimensionality reduction

<p>Abstract</p> <p>Background</p> <p>Multifactor Dimensionality Reduction (MDR) has been introduced previously as a non-parametric statistical method for detecting gene-gene interactions. MDR performs a dimensional reduction by assigning multi-locus genotypes to either high- or low-risk groups and measuring the percentage of cases and controls incorrectly labelled by this classification – the classification error. The combination of variables that produces the lowest classification error is selected as the best or most fit model. The correctly and incorrectly labelled cases and controls can be expressed as a two-way contingency table. We sought to improve the ability of MDR to detect gene-gene interactions by replacing classification error with a different measure to score model quality.</p> <p>Results</p> <p>In this study, we compare the detection and power of MDR using a variety of measures for two-way contingency table analysis. We simulated 40 genetic models, varying the number of disease loci in the model (2 – 5), allele frequencies of the disease loci (.2/.8 or .4/.6) and the broad-sense heritability of the model (.05 – .3). Overall, detection using NMI was 65.36% across all models, and specific detection was 59.4% versus detection using classification error at 62% and specific detection was 52.2%.</p> <p>Conclusion</p> <p>Of the 10 measures evaluated, the likelihood ratio and normalized mutual information (NMI) are measures that consistently improve the detection and power of MDR in simulated data over using classification error. These measures also reduce the inclusion of spurious variables in a multi-locus model. Thus, MDR, which has already been demonstrated as a powerful tool for detecting gene-gene interactions, can be improved with the use of alternative fitness functions.</p

The Laser Communications Relay Demonstration Experiment Program

This paper elaborates on the Laser Communications Relay Demonstration (LCRD) Experiment Program, which will engage in a number of pre-determined experiments and also call upon a wide variety of experimenters to test new laser communications technology and techniques, and to gather valuable data. LCRD is a joint project between NASA's Goddard Space Flight Center (GSFC), the Jet Propulsion Laboratory (JPL), and the Massachusetts Institute of Technology Lincoln Laboratory (MIT LL). LCRD will test the functionality in various settings and scenarios of optical communications links from a GEO (Geosynchronous Earth Orbit) payload to ground stations in Southern California and Hawaii over a two-year period following launch in 2019. The LCRD investigator team will execute numerous experiments to test critical aspects of laser communications activities over real links and systems, collecting data on the effects of atmospheric turbulence and weather on performance and communications availability. LCRD will also incorporate emulations of target scenarios, including direct-to-Earth (DTE) links from user spacecraft and optical relay providers supporting user spacecraft. To supplement and expand upon the results of these experiments, the project also includes a Guest Experimenters Program, which encourages individuals and groups from government agencies, academia and industry to propose diverse experiment ideas