Content Distribution by Multiple Multicast Trees and Intersession Cooperation: Optimal Algorithms and Approximations

In traditional massive content distribution with multiple sessions, the sessions form separate overlay networks and operate independently, where some sessions may suffer from insufficient resources even though other sessions have excessive resources. To cope with this problem, we consider the universal swarming approach, which allows multiple sessions to cooperate with each other. We formulate the problem of finding the optimal resource allocation to maximize the sum of the session utilities and present a subgradient algorithm which converges to the optimal solution in the time-average sense. The solution involves an NP-hard subproblem of finding a minimum-cost Steiner tree. We cope with this difficulty by using a column generation method, which reduces the number of Steiner-tree computations. Furthermore, we allow the use of approximate solutions to the Steiner-tree subproblem. We show that the approximation ratio to the overall problem turns out to be no less than the reciprocal of the approximation ratio to the Steiner-tree subproblem. Simulation results demonstrate that universal swarming improves the performance of resource-poor sessions with negligible impact to resource-rich sessions. The proposed approach and algorithm are expected to be useful for infrastructure-based content distribution networks with long-lasting sessions and relatively stable network environment

Impacts of climate change on TN load and its control in a River Basin with complex pollution sources

It is increasingly recognized that climate change could affect the quality of water through complex natural and anthropogenic mechanisms. Previous studies on climate change and water quality have mostly focused on assessing its impact on pollutant loads from agricultural runoff. A sub-daily SWAT model was developed to simulate the discharge, transport, and transformation of nitrogen from all known anthropogenic sources including industries, municipal sewage treatment plants, concentrated and scattered feedlot operations, rural households, and crop production in the Upper Huai River Basin. This is a highly polluted basin with total nitrogen (TN) concentrations frequently exceeding Class V of the Chinese Surface Water Quality Standard (GB3838-2002). Climate change projections produced by 16 Global Circulation Models (GCMs) under the RCP 4.5 and RCP 8.5 scenarios in the mid (2040–2060) and late (2070–2090) century were used to drive the SWAT model to evaluate the impacts of climate change on both the TN loads and the effectiveness of three water pollution control measures (reducing fertilizer use, constructing vegetative filter strips, and improving septic tank performance) in the basin. SWAT simulation results have indicated that climate change is likely to cause an increase in both monthly average and extreme TN loads in February, May, and November. The projected impact of climate change on TN loads in August is more varied between GCMs. In addition, climate change is projected to have a negative impact on the effectiveness of septic tanks in reducing TN loads, while its impacts on the other two measures are more uncertain. Despite the uncertainty, reducing fertilizer use remains the most effective measure for reducing TN loads under different climate change scenarios. Meanwhile, improving septic tank performance is relatively more effective in reducing annual TN loads, while constructing vegetative filter strips is more effective in reducing annual maximum monthly TN loads

Genetic Association Study with Metabolic Syndrome and Metabolic-Related Traits in a Cross-Sectional Sample and a 10-Year Longitudinal Sample of Chinese Elderly Population

Background: The metabolic syndrome (MetS) has been known as partly heritable, while the number of genetic studies on MetS and metabolic-related traits among Chinese elderly was limited. Methods: A cross-sectional analysis was performed among 2 014 aged participants from September 2009 to June 2010 in Beijing, China. An additional longitudinal study was carried out among the same study population from 2001 to 2010. Biochemical profile and anthropometric parameters of all the participants were measured. The associations of 23 SNPs located within 17 candidate genes (MTHFR, PPARγ, LPL, INSIG, TCF7L2, FTO, KCNJ11, JAZF1, CDKN2A/B, ADIPOQ, WFS1, CDKAL1, IGF2BP2, KCNQ1, MTNR1B, IRS1, ACE) with overweight and obesity, diabetes, metabolic phenotypes, and MetS were examined in both studies. Results: In this Chinese elderly population, prevalence of overweight, central obesity, diabetes, dyslipidemia, hypertension, and MetS were 48.3%, 71.0%, 32.4%, 75.7%, 68.3% and 54.5%, respectively. In the cross-sectional analyses, no SNP was found to be associated with MetS. Genotype TT of SNP rs4402960 within the gene IGF2BP2 was associated with overweight (odds ratio (OR) = 0.479, 95% confidence interval (CI): 0.316-0.724, p = 0.001) and genotype CA of SNP rs1801131 within the gene MTHFR was associated with hypertension (OR = 1.560, 95% CI: 1.194–2.240, p = 0.001). However, these associations were not observed in the longitudinal analyses. Conclusions: The associations of SNP rs4402960 with overweight as well as the association of SNP rs1801131 with hypertension were found to be statistically significant. No SNP was identified to be associated with MetS in our study with statistical significance

A mutational analysis and molecular dynamics simulation of quinolone resistance proteins QnrA1 and QnrC from Proteus mirabilis

<p>Abstract</p> <p>Background</p> <p>The first report on the transferable, plasmid-mediated quinolone-resistance determinant <it>qnrA1 </it>was in 1998. Since then, <it>qnr </it>alleles have been discovered worldwide in clinical strains of Gram-negative bacilli. Qnr proteins confer quinolone resistance, and belong to the pentapeptide repeat protein (PRP) family. Several PRP crystal structures have been solved, but little is known about the functional significance of their structural arrangement.</p> <p>Results</p> <p>We conducted random and site-directed mutagenesis on <it>qnrA1 </it>and on <it>qnrC</it>, a newly identified quinolone-resistance gene from <it>Proteus mirabilis</it>. Many of the Qnr mutants lost their quinolone resistance function. The highly conserved hydrophobic Leu or Phe residues at the center of the pentapeptide repeats are known as <it>i </it>sites, and loss-of-function mutations included replacement of the <it>i </it>site hydrophobic residues with charged residues, replacing the <it>i</it>^-2site, N-terminal to the <it>i </it>residues, with bulky side-chain residues, introducing Pro into the β-helix coil, deletion of the N- and C-termini, and excision of a central coil. Molecular dynamics simulations and homology modeling demonstrated that QnrC overall adopts a stable β-helix fold and shares more similarities with MfpA than with other PRP structures. Based on homology modeling and molecular dynamics simulation, the dysfunctional point mutations introduced structural deformations into the quadrilateral β-helix structure of PRPs. Of the pentapeptides of QnrC, two-thirds adopted a type II β-turn, while the rest adopted type IV turns. A gap exists between coil 2 and coil 3 in the QnrC model structure, introducing a structural flexibility that is similar to that seen in MfpA.</p> <p>Conclusion</p> <p>The hydrophobic core and the β-helix backbone conformation are important for maintaining the quinolone resistance property of Qnr proteins. QnrC may share structural similarity with MfpA.</p

Hormone-Induced 14-3-3γ Adaptor Protein Regulates Steroidogenic Acute Regulatory Protein Activity and Steroid Biosynthesis in MA-10 Leydig Cells

Cholesterol is the sole precursor of steroid hormones in the body. The import of cholesterol to the inner mitochondrial membrane, the rate-limiting step in steroid biosynthesis, relies on the formation of a protein complex that assembles at the outer mitochondrial membrane called the transduceosome. The transduceosome contains several mitochondrial and cytosolic components, including the steroidogenic acute regulatory protein (STAR). Human chorionic gonadotropin (hCG) induces de novo synthesis of STAR, a process shown to parallel maximal steroid production. In the hCG-dependent steroidogenic MA-10 mouse Leydig cell line, the 14-3-3γ protein was identified in native mitochondrial complexes by mass spectrometry and immunoblotting, and its levels increased in response to hCG treatment. The 14-3-3 proteins bind and regulate the activity of many proteins, acting via target protein activation, modification and localization. In MA-10 cells, cAMP induces 14-3-3γ expression parallel to STAR expression. Silencing of 14-3-3γ expression potentiates hormone-induced steroidogenesis. Binding motifs of 14-3-3γ were identified in components of the transduceosome, including STAR. Immunoprecipitation studies demonstrate a hormone-dependent interaction between 14-3-3γ and STAR that coincides with reduced 14-3-3γ homodimerization. The binding site of 14-3-3γ on STAR was identified to be Ser-194 in the STAR-related sterol binding lipid transfer (START) domain, the site phosphorylated in response to hCG. Taken together, these results demonstrate that 14-3-3γ negatively regulates steroidogenesis by binding to Ser-194 of STAR, thus keeping STAR in an unfolded state, unable to induce maximal steroidogenesis. Over time 14-3-3γ homodimerizes and dissociates from STAR, allowing this protein to induce maximal mitochondrial steroid formation