Crux: Locality-Preserving Distributed Services

Distributed systems achieve scalability by distributing load across many machines, but wide-area deployments can introduce worst-case response latencies proportional to the network's diameter. Crux is a general framework to build locality-preserving distributed systems, by transforming an existing scalable distributed algorithm A into a new locality-preserving algorithm ALP, which guarantees for any two clients u and v interacting via ALP that their interactions exhibit worst-case response latencies proportional to the network latency between u and v. Crux builds on compact-routing theory, but generalizes these techniques beyond routing applications. Crux provides weak and strong consistency flavors, and shows latency improvements for localized interactions in both cases, specifically up to several orders of magnitude for weakly-consistent Crux (from roughly 900ms to 1ms). We deployed on PlanetLab locality-preserving versions of a Memcached distributed cache, a Bamboo distributed hash table, and a Redis publish/subscribe. Our results indicate that Crux is effective and applicable to a variety of existing distributed algorithms.Comment: 11 figure

Mineral Resources of the Marble Canyon Wilderness Study Area, White Pine County, Nevada, and Millard County, Utah

The 19,150-acre Marble Canyon Wilderness Study Area (NV-040-086) was evaluated for mineral resources (known) and mineral resource potential (undiscovered), and field work was conducted in 1987. The acreage includes 6,435 acres that is now designated as part of the Mount Moriah Wilderness under the Nevada Wilderness Protection Act of 1989 (S. 974), most but not all of which is included in 8,300 acres fro which the U.S. Bureau of Land Management requested a mineral survey. In this report, the wilderness study area, or simply the study area refers to the entire 19,150-acre tract. The area in underlain by quartzite shale and carbonate rocks. The norther Snake Range decollement is a detachment surface within the study area that separates rocks of similar age but different metamorphic grade. Large inferred subeconomic limestone and marble resources i the study area have no special or unique properties. The mineral resource potential for limestone and marble is high in two canyons and is moderate in the rest of the wilderness study area. Parts of the study area above and along the northern Snake Range decollement have low potential for undiscovered deposits of gold, silver, copper, lead, zinc, tungsten, molybdenum, beryllium, and flourite. A zone around barite-bearing rock penetrated by adits inside the southeast boundary of the study area has moderate potential for barite, and the surrounding area has low potential for barite; both areas also have low potential for silver, copper, lead, zinc, and tungsten. The entire study area has moderate potential for oil and gas and low potential for geothermal energy resources

First Report of Circulating MicroRNAs in Tumour Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS)

Tumor necrosis factor-receptor associated periodic syndrome (TRAPS) is a rare autosomal dominant autoinflammatory disorder characterized by recurrent episodes of long-lasting fever and inflammation in different regions of the body, such as the musculo-skeletal system, skin, gastrointestinal tract, serosal membranes and eye. Our aims were to evaluate circulating microRNAs (miRNAs) levels in patients with TRAPS, in comparison to controls without inflammatory diseases, and to correlate their levels with parameters of disease activity and/or disease severity. Expression levels of circulating miRNAs were measured by Agilent microarrays in 29 serum samples from 15 TRAPS patients carrying mutations known to be associated with high disease penetrance and from 8 controls without inflammatory diseases. Differentially expressed and clinically relevant miRNAs were detected using GeneSpring GX software. We identified a 6 miRNAs signature able to discriminate TRAPS from controls. Moreover, 4 miRNAs were differentially expressed between patients treated with the interleukin (IL)-1 receptor antagonist, anakinra, and untreated patients. Of these, miR-92a-3p and miR-150-3p expression was found to be significantly reduced in untreated patients, while their expression levels were similar to controls in samples obtained during anakinra treatment. MiR-92b levels were inversely correlated with the number of fever attacks/year during the 1st year from the index attack of TRAPS, while miR-377-5p levels were positively correlated with serum amyloid A (SAA) circulating levels. Our data suggest that serum miRNA levels show a baseline pattern in TRAPS, and may serve as potential markers of response to therapeutic intervention

Target selection and annotation for the structural genomics of the amidohydrolase and enolase superfamilies

To study the substrate specificity of enzymes, we use the amidohydrolase and enolase superfamilies as model systems; members of these superfamilies share a common TIM barrel fold and catalyze a wide range of chemical reactions. Here, we describe a collaboration between the Enzyme Specificity Consortium (ENSPEC) and the New York SGX Research Center for Structural Genomics (NYSGXRC) that aims to maximize the structural coverage of the amidohydrolase and enolase superfamilies. Using sequence- and structure-based protein comparisons, we first selected 535 target proteins from a variety of genomes for high-throughput structure determination by X-ray crystallography; 63 of these targets were not previously annotated as superfamily members. To date, 20 unique amidohydrolase and 41 unique enolase structures have been determined, increasing the fraction of sequences in the two superfamilies that can be modeled based on at least 30% sequence identity from 45% to 73%. We present case studies of proteins related to uronate isomerase (an amidohydrolase superfamily member) and mandelate racemase (an enolase superfamily member), to illustrate how this structure-focused approach can be used to generate hypotheses about sequence–structure–function relationships

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

A Web Service Recommender System Using Enhanced Syntactical Matching

Service-oriented computing (SOC) enables organizations and individual users to discover openly-accessible capabilities realized as services over the Internet. However, service registries can potentially be very large preventing organizations from discovering services in real-time. In fact, consumers may not be aware of the services that can be of most benefit to them. In our work, we introduce a web service recommender system that proactively discovers and manages web services. This paper focuses on the underlying search and ranking algorithms that enable the recommendations. As an innovation, we have analyzed real, fully-operational web services currently available on the Internet and, as a result, have discovered insights into how real web service messages are defined. Using these general naming tendencies coupled with enhanced syntactical methods, we are able to aggregate services by their messages and accurately suggest candidate services to users as a part of daily routines

Predicting Service Mashup Candidates Using Enhanced Syntactical Message Management

The descriptiveness of capabilities advertised on service-oriented architectures provides a promising platform for crafting new knowledge. Service mashup has been introduced as an approach for integrating the information provided from multiple web services into one common operational picture. In the future, scale will be a barrier to these types of approaches. With the entry and exit of large numbers of services on the Internet, it will be difficult to find and suggest the most relevant service candidates for new mashups. In this work, we present an efficient syntactical approach for actively discovering web service candidates for service mashups. This approach leverages the message naming characteristics of the developers and of the target service repository to inform search algorithms. Favorable precision results are described based on experimentation executed on an open repository of web service from the Internet