Algorithms for Replica Placement in High-Availability Storage

A new model of causal failure is presented and used to solve a novel replica placement problem in data centers. The model describes dependencies among system components as a directed graph. A replica placement is defined as a subset of vertices in such a graph. A criterion for optimizing replica placements is formalized and explained. In this work, the optimization goal is to avoid choosing placements in which a single failure event is likely to wipe out multiple replicas. Using this criterion, a fast algorithm is given for the scenario in which the dependency model is a tree. The main contribution of the paper is an $O(n + \rho \log \rho)$ dynamic programming algorithm for placing $\rho$ replicas on a tree with $n$ vertices. This algorithm exhibits the interesting property that only two subproblems need to be recursively considered at each stage. An $O(n^2 \rho)$ greedy algorithm is also briefly reported.Comment: 22 pages, 7 figures, 4 algorithm listing

In situ loading and delivery of short single- And double-stranded dna by supramolecular organic frameworks

Short DNA represents an important class of biomacromolecules that are widely applied in gene therapy, editing, and modulation. However, the development of simple and reliable methods for their intracellular delivery remains a challenge. Herein, we describe that seven water-soluble, homogeneous supramolecular organic frameworks (SOFs) with a well-defined pore size and high stability in water that can accomplish in situ inclusion of single-stranded (ss) and double-stranded (ds) DNA (21, 23, and 58 nt) and effective intracellular delivery (including two noncancerous and six cancerous cell lines). Fluorescence quenching experiments for single and double endlabeled ss- and ds-DNA support that the DNA sequences can be completely enveloped by the SOFs. Confocal laser scanning microscopy and flow cytometry reveal that five of the SOFs exhibit excellent delivery efficiencies that, in most of the studied cases, outperform the commercial standard Lipo2000, even at low SOF-nucleic acid ratios. In addition to high delivery efficiencies, the watersoluble, self-assembled SOF carriers have a variety of advantages, including convenient preparation, high stability, and in situ DNA inclusion, which are all critical for practical applications in nucleic acid delivery

Weakening of the stratospheric polar vortex by Arctic sea-ice loss

Successive cold winters of severely low temperatures in recent years have had critical social and economic impacts on the mid-latitude continents in the Northern Hemisphere. Although these cold winters are thought to be partly driven by dramatic losses of Arctic sea-ice, the mechanism that links sea-ice loss to cold winters remains a subject of debate. Here, by conducting observational analyses and model experiments, we show how Arctic sea-ice loss and cold winters in extra-polar regions are dynamically connected through the polar stratosphere. We find that decreased sea-ice cover during early winter months (November-December), especially over the Barents-Kara seas, enhances the upward propagation of planetary-scale waves with wavenumbers of 1 and 2, subsequently weakening the stratospheric polar vortex in mid-winter (January-February). The weakened polar vortex preferentially induces a negative phase of Arctic Oscillation at the surface, resulting in low temperatures in mid-latitudes.open11167174Ysciescopu

Isolation and characterization of Rhodococcus ruber CGMCC3090 that hydrolyzes aliphatic, aromatic and heterocyclic nitriles

A bacterial strain was isolated from soil samples that had been polluted by nitrile compounds. This strain converts acrylonitrile to acrylamide with high activity. The nitrile hydrolysis activity was tested using eight substrates, including aliphatic, aromatic and heterocyclic (di)nitriles. All of the nitrilecompounds were hydrolyzed by the resting cells. The main (cyano-)amide products demonstrated that nitrile hydratase was abundantly produced in this strain and that it mediated monohydrolysis. The specific conversion rate decreased in the following order: acrylonitrile > 3-cyanopyridine > valeronitrile> adiponitrile > 2,3,4,5,6-pentafluorobenzonitrile >  -hydroxyphenylacetonitrile > 3-indoleaceto-nitrile > phthalonitrile, suggesting a higher conversion capability towards aliphatic nitriles. The strain that hadbroad substrate spectra was identified and named Rhodococcus ruber CGMCC3090 based on the 16S rDNA sequence

A Lentivirus-Mediated Genetic Screen Identifies Dihydrofolate Reductase (DHFR) as a Modulator of β-Catenin/GSK3 Signaling

The multi-protein β-catenin destruction complex tightly regulates β-catenin protein levels by shuttling β-catenin to the proteasome. Glycogen synthase kinase 3β (GSK3β), a key serine/threonine kinase in the destruction complex, is responsible for several phosphorylation events that mark β-catenin for ubiquitination and subsequent degradation. Because modulation of both β-catenin and GSK3β activity may have important implications for treating disease, a complete understanding of the mechanisms that regulate the β-catenin/GSK3β interaction is warranted. We screened an arrayed lentivirus library expressing small hairpin RNAs (shRNAs) targeting 5,201 human druggable genes for silencing events that activate a β-catenin pathway reporter (BAR) in synergy with 6-bromoindirubin-3′oxime (BIO), a specific inhibitor of GSK3β. Top screen hits included shRNAs targeting dihydrofolate reductase (DHFR), the target of the anti-inflammatory compound methotrexate. Exposure of cells to BIO plus methotrexate resulted in potent synergistic activation of BAR activity, reduction of β-catenin phosphorylation at GSK3-specific sites, and accumulation of nuclear β-catenin. Furthermore, the observed synergy correlated with inhibitory phosphorylation of GSK3β and was neutralized upon inhibition of phosphatidyl inositol 3-kinase (PI3K). Linking these observations to inflammation, we also observed synergistic inhibition of lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines (TNFα, IL-6, and IL-12), and increased production of the anti-inflammatory cytokine IL-10 in peripheral blood mononuclear cells exposed to GSK3 inhibitors and methotrexate. Our data establish DHFR as a novel modulator of β-catenin and GSK3 signaling and raise several implications for clinical use of combined methotrexate and GSK3 inhibitors as treatment for inflammatory disease

A Simple Method to Synthesize Cadmium Hydroxide Nanobelts

Cd(OH)2nanobelts have been synthesized in high yield by a convenient polyol method for the first time. XRD, XPS, FESEM, and TEM were used to characterize the product, which revealed that the product consisted of belt-like crystals about 40 nm in thickness and length up to several hundreds of micrometers. Studies found that the viscosity of the solvent has important influence on the morphology of the final products. The optical absorption spectrum indicates that the Cd(OH)2nanobelts have a direct band gap of 4.45 eV

An increased prevalence of self-reported allergic rhinitis in major Chinese cities from 2005 to 2011

Background: The prevalence of allergic rhinitis (AR) has increased worldwide in recent decades. This study was conducted to investigate the prevalence of self-reported AR and profiles of AR-related comorbidities in the adult population of China over time. Methods: This study surveyed residents of 18 major cities in mainland China. Telephone interviews were conducted with study participants after sampling target telephone numbers by random digit dialing. The questions asked during telephone interviews were based on those included in validated questionnaires and focused on topics regarding AR, nonallergic rhinitis (NAR), acute/chronic rhinosinusitis (ARS/CRS), asthma, and atopic dermatitis (AD). Results: During 2011, a total of 47216 telephone interviews were conducted, and the overall response rate was 77.5%. When compared with the AR prevalence in 11 cities surveyed in 2005, there was a significant increase in self-reported adult AR in eight of those cities (P<0.01). In 2011, the standardized prevalence of self-reported adult AR in the 18 cities was 17.6%. The concentration of SO2 was positively correlated with the prevalence of AR (r=0.504, P=0.033). A multiple regression model showed that the absolute change in household yearly income was significantly associated with the change in the prevalence of AR (R-2=0.68), after adjusting for PM10, SO2, NO2, temperature, and humidity. The overall prevalences of NAR, ARS, CRS, asthma, and AD in the general population were 16.4%, 5.4%, 2.1%, 5.8%, and 14%, respectively. Conclusion: During a 6-year period, there was a significant increase in the prevalence of self-reported AR in the general Chinese adult population. The incidence of AR being accompanied by rhinosinusitis, asthma, or AD was significantly higher among individuals having self-reported AR compared with the general population

Calmodulin in complex with the first IQ motif of myosin-5a functions as an intact calcium sensor

© 2016, National Academy of Sciences. All rights reserved. The motor function of vertebrate myosin-5a is inhibited by its tail in a Ca2+-dependent manner. We previously demonstrated that the calmodulin (CaM) bound to the first isoleucine-glutamine (IQ) motif (IQ1) of myosin-5a is responsible for the Ca2+-dependent regulation of myosin-5a. We have solved the crystal structure of a truncated myosin-5a containing the motor domain and IQ1 (MD-IQ1) complexed with Ca2+-bound CaM (Ca2+-CaM) at 2.5-Å resolution. Compared with the structure of the MD-IQ1 complexed with essential light chain (an equivalent of apo-CaM), MD-IQ1/Ca2+-CaM displays large conformational differences in IQ1/CaM and little difference in the motor domain. In the MD-IQ1/Ca2+-CaM structure, the N-lobe and the C-lobe of Ca2+-CaM adopt an open conformation and grip the C-terminal and the N-terminal portions of the IQ1, respectively. Remarkably, the interlobe linker of CaM in IQ1/Ca2+-CaM is in a position opposite that in IQ1/apo-CaM, suggesting that CaM flip-flops relative to the IQ1 during the Ca2+ transition. We demonstrated that CaM continuously associates with the IQ1 during the Ca2+ transition and that the binding of CaM to IQ1 increases Ca2+ affinity and substantially changes the kinetics of the Ca2+ transition, suggesting that the IQ1/CaM complex functions as an intact Ca2+ sensor responding to distinct calcium signals

Effects of Edge Functional Groups on Water Transport in Graphene Oxide Membranes

Graphene oxide (GO) membranes assembled by GO nanosheets exhibit high water flux because of the unique water channels formed by their functionalized layer-by-layer structure. Although water transport in the GO membrane is in principle influenced by the functional groups at the edges of GO nanosheets, this is yet to be fully understood. To fill this knowledge gap, molecular dynamics simulation was employed in this work to gain insights into the influences of three typical edge functional groups of GO nanosheets: Carboxyl (COOH), hydroxyl (OH), and hydrogen (H). A well-controlled numerical analysis with complete isolation of the functional groups at the edges was undertaken. The results reveal that the COOH group has a negative impact on water transport because of its relatively large steric geometric structure, which resists water flow. By contrast, the OH group promotes water transport by uniquely "pulling" water molecules across the nanosheet layer because of its relatively stronger interaction with water. The H atom promotes water transport as well, mainly because of its low-resistance steric structure. Moreover, the size of the inter-edge hub has an apparent impact on the influence of these functional groups on water transport. The results suggest that in the design of high water flux GO membranes, it would be strategic to remove COOH edge functional groups while maintaining a mixture of OH and H edge functional groups