Interest-based RDF Update Propagation

Many LOD datasets, such as DBpedia and LinkedGeoData, are voluminous and process large amounts of requests from diverse applications. Many data products and services rely on full or partial local LOD replications to ensure faster querying and processing. While such replicas enhance the flexibility of information sharing and integration infrastructures, they also introduce data duplication with all the associated undesirable consequences. Given the evolving nature of the original and authoritative datasets, to ensure consistent and up-to-date replicas frequent replacements are required at a great cost. In this paper, we introduce an approach for interest-based RDF update propagation, which propagates only interesting parts of updates from the source to the target dataset. Effectively, this enables remote applications to `subscribe' to relevant datasets and consistently reflect the necessary changes locally without the need to frequently replace the entire dataset (or a relevant subset). Our approach is based on a formal definition for graph-pattern-based interest expressions that is used to filter interesting parts of updates from the source. We implement the approach in the iRap framework and perform a comprehensive evaluation based on DBpedia Live updates, to confirm the validity and value of our approach.Comment: 16 pages, Keywords: Change Propagation, Dataset Dynamics, Linked Data, Replicatio

Diet-induced early-stage atherosclerosis in baboons: lipoproteins, atherogenesis, and arterial compliance

Background The purpose of this study was to determine if dietary manipulation can reliably induce early-stage atherosclerosis and clinically relevant changes in vascular function in an established, well-characterized nonhuman primate model. Methods We fed 112 baboons a high cholesterol, high fat challenge diet for two years. We assayed circulating biomarkers of cardiovascular disease (CVD) risk, at 0, 7, and 104 weeks into the challenge; assessed arterial compliance noninvasively at 104 weeks; and measured atherosclerotic lesions in three major arteries at necropsy. Results We observed evidence of atherosclerosis in all but one baboon fed the two-year challenge diet. CVD risk biomarkers, the prevalence, size, and complexity of arterial lesions, plus consequent arterial stiffness, were increased in comparison to dietary control animals. Conclusions Feeding baboons a high cholesterol, high fat diet for two years reliably induces atherosclerosis, with risk factor profiles, arterial lesions, and changes in vascular function also seen in humans

Elucidation of the Hsp90 C-terminal Inhibitor Binding Site

The Hsp90 chaperone machine is required for the folding, activation and/or stabilization of more than 50 proteins directly related to malignant progression. Hsp90 contains small molecule binding sites at both its N- and C-terminal domains, however, limited structural and biochemical data regarding the C-terminal binding site is available. In this report, the small molecule binding site in the Hsp90 C-terminal domain was revealed by protease fingerprinting and photoaffinity labeling utilizing LC-MS/MS. The identified site was characterized by generation of a homology model for hHsp90α using the SAXS open structure of HtpG and docking the bioactive conformation of NB into the generated model. The resulting model for the bioactive conformation of NB bound to Hsp90α is presented herein

Genetics of kidney disease and related cardiometabolic phenotypes in Zuni Indians: the Zuni Kidney Project

The objective of this study is to identify genetic factors associated with chronic kidney disease (CKD) and related cardiometabolic phenotypes among participants of the Genetics of Kidney Disease in Zuni Indians study. The study was conducted as a community-based participatory research project in the Zuni Indians, a small endogamous tribe in rural New Mexico. We recruited 998 members from 28 extended multigenerational families, ascertained through probands with CKD who had at least one sibling with CKD. We used the Illumina Infinium Human1M-Duo version 3.0 BeadChips to type 1.1 million single nucleotide polymorphisms (SNPs). Prevalence estimates for CKD, hyperuricemia, diabetes, and hypertension were 24%, 30%, 17% and 34%, respectively. We found a significant (p \u3c 1.58 × 10-7) association for a SNP in a novel gene for serum creatinine (PTPLAD2). We replicated significant associations for genes with serum uric acid (SLC2A9), triglyceride levels (APOA1, BUD13, ZNF259), and total cholesterol (PVRL2). We found novel suggestive associations (p \u3c 1.58 × 10-6) for SNPs in genes with systolic (OLFML2B), and diastolic blood pressure (NFIA). We identified a series of genes associated with CKD and related cardiometabolic phenotypes among Zuni Indians, a population with a high prevalence of kidney disease. Illuminating genetic variations that modulate the risk for these disorders may ultimately provide a basis for novel preventive strategies and therapeutic interventions

Memory function approach to the Hall constant in strongly correlated electron systems

The anomalous properties of the Hall constant in the normal state of high-$T_c$ superconductors are investigated within the single-band Hubbard model. We argue that the Mori theory is the appropriate formalism to address the Hall constant, since it aims directly at resistivities rather than conductivities. More specifically, the frequency dependent Hall constant decomposes into its infinite frequency limit and a memory function contribution. As a first step, both terms are calculated perturbatively in $U$ and on an infinite dimensional lattice, where $U$ is the correlation strength. If we allow $U$ to be of the order of twice the bare band width, the memory function contribution causes the Hall constant to change sign as a function of doping and to decrease as a function of temperature.Comment: 35 pages, RevTex, 3 ps figures include

AMPT-induced monoamine depletion in humans: evaluation of two alternative [123I]IBZM SPECT procedures

Purpose Acute monoamine depletion paradigms using alpha-methyl-para-tyrosine (AMPT) combined with single photon emission computed tomography (SPECT) have been used successfully to evaluate disturbances in central dopaminergic neurotransmission. However, severe side effects due to relatively high doses (4,500 to 8,000 mg) of AMPT have been reasons for study withdrawal. Thus, we assessed the effectiveness and tolerability of two alternative procedures, using lower doses of AMPT. Methods Six healthy subjects underwent three measurements of striatal dopamine D2 receptor (D2R)-binding potential (BPND) with SPECT and the selective radiolabeled D2R antagonist [123I]IBZM. All subjects were scanned in the absence of pharmacological intervention (baseline) and after two different depletion procedures. In the first depletion session, over 6 h, subjects were administered 1,500 mg of AMPT before scanning. In the second depletion session, over 25 h, subjects were administered 40 mg AMPT/kg body weight. We also administered the Subjective Well-being Under Neuroleptic Treatment Scale, a self-report instrument designed to measure the subjective experience of patients on neuroleptic medication. Results We found no change of mean D2R BPND after the first and short AMPT challenge compared to the baseline. However, we found a significant increase in striatal D2R BPND binding after the AMPT challenge adjusted for bodyweight compared to both other regimen. Although subjective well-being worsened after the prolonged AMPT challenge, no severe side effects were reported. Conclusions Our results imply a low-dosage, suitable alternative to the common AMPT procedure. The probability of side effects and study withdrawal can be reduced by this procedure

Subjective response to antipsychotic treatment and compliance in schizophrenia. A naturalistic study comparing olanzapine, risperidone and haloperidol (EFESO Study)

BACKGROUND: In order to compare the effectiveness of different antipsychotic drugs in the treatment of schizophrenia it is very important to evaluate subjective response and compliance in patient cohorts treated according to routine clinical practice. METHOD: Outpatients with schizophrenia entered this prospective, naturalistic study when they received a new prescription for an antipsychotic drug. Treatment assignment was based on purely clinical criteria, as the study did not include any experimental intervention. Patients treated with olanzapine, risperidone or haloperidol were included in the analysis. Subjective response was measured using the 10-item version of the Drug Attitude Inventory (DAI-10), and treatment compliance was measured using a physician-rated 4 point categorical scale. RESULTS: A total of 2128 patients initiated treatment (as monotherapy) with olanzapine, 417 with risperidone, and 112 with haloperidol. Olanzapine-treated patients had significantly higher DAI-10 scores and significantly better treatment compliance compared to both risperidone- and haloperidol-treated patients. Risperidone-treated patients had a significantly higher DAI-10 score compared to haloperidol-treated patients. CONCLUSION: Subjective response and compliance were superior in olanzapine-treated patients, compared to patients treated with risperidone and haloperidol, in routine clinical practice. Differences in subjective response were explained largely, but not completely, by differences in incidence of EPS

The effect of antipsychotic medication on sexual function and serum prolactin levels in community-treated schizophrenic patients: results from the Schizophrenia Trial of Aripiprazole (STAR) study (NCT00237913)

<p>Abstract</p> <p>Background</p> <p>The aim of this paper is to evaluate the effect of antipsychotics for the treatment of schizophrenia in a community based study on sexual function and prolactin levels comparing the use of aripiprazole and standard of care (SOC), which was a limited choice of three widely used and available antipsychotics (olanzapine, quetiapine or risperidone) (The Schizophrenia Trial of Aripiprazole [STAR] study [NCT00237913]).</p> <p>Method</p> <p>This open-label, 26-week, multi-centre, randomised study compared aripiprazole to SOC (olanzapine, quetiapine or risperidone) in patients with schizophrenia (DSM-IV-TR criteria). The primary effectiveness variable was the mean total score of the Investigator Assessment Questionnaire (IAQ) at Week 26. The outcome research variables included the Arizona Sexual Experience scale (ASEX). This along with the data collected on serum prolactin levels at week 4, 8, 12, 18 and 26 will be the focus of this paper.</p> <p>Results</p> <p>A total of 555 patients were randomised to receive aripiprazole (n = 284) or SOC (n = 271). Both treatment groups experienced improvements in sexual function from baseline ASEX assessments. However at 8 weeks the aripiprazole treatment group reported significantly greater improvement compared with the SOC group (p = 0.007; OC). Although baseline mean serum prolactin levels were similar in the two treatment groups (43.4 mg/dL in the aripiprazole group and 42.3 mg/dL in the SOC group, p = NS) at Week 26 OC, mean decreases in serum prolactin were 34.2 mg/dL in the aripiprazole group, compared with 13.3 mg/dL in the SOC group (p < 0.001).</p> <p>Conclusion</p> <p>The study findings suggest that aripiprazole has the potential to reduce sexual dysfunction, which in turn might improve patient compliance.</p

Consistent Directions of Effect for Established Type 2 Diabetes Risk Variants Across Populations: The Population Architecture using Genomics and Epidemiology (PAGE) Consortium

Common genetic risk variants for type 2 diabetes (T2D) have primarily been identified in populations of European and Asian ancestry. We tested whether the direction of association with 20 T2D risk variants generalizes across six major racial/ethnic groups in the U.S. as part of the Population Architecture using Genomics and Epidemiology Consortium (16,235 diabetes case and 46,122 control subjects of European American, African American, Hispanic, East Asian, American Indian, and Native Hawaiian ancestry). The percentage of positive (odds ratio [OR] >1 for putative risk allele) associations ranged from 69% in American Indians to 100% in European Americans. Of the nine variants where we observed significant heterogeneity of effect by racial/ethnic group (Pheterogeneity 1) in at least five groups. The marked directional consistency of association observed for most genetic variants across populations implies a shared functional common variant in each region. Fine-mapping of all loci will be required to reveal markers of risk that are important within and across populations

Genome-wide association of trajectories of systolic blood pressure change

Abstract Background There is great interindividual variation in systolic blood pressure (SBP) as a result of the influences of several factors, including sex, ancestry, smoking status, medication use, and, especially, age. The majority of genetic studies have examined SBP measured cross-sectionally; however, SBP changes over time, and not necessarily in a linear fashion. Therefore, this study conducted a genome-wide association (GWA) study of SBP change trajectories using data available through the Genetic Analysis Workshop 19 (GAW19) of 959 individuals from 20 extended Mexican American families from the San Antonio Family Studies with up to 4 measures of SBP. We performed structural equation modeling (SEM) while taking into account potential genetic effects to identify how, if at all, to include covariates in estimating the SBP change trajectories using a mixture model based latent class growth modeling (LCGM) approach for use in the GWA analyses. Results The semiparametric LCGM approach identified 5 trajectory classes that captured SBP changes across age. Each LCGM identified trajectory group was ranked based on the average number of cumulative years as hypertensive. Using a pairwise comparison of these classes the heritability estimates range from 12 to 94 % (SE = 17 to 40 %). Conclusion These identified trajectories are significantly heritable, and we identified a total of 8 promising loci that influence one’s trajectory in SBP change across age. Our results demonstrate the potential utility of capitalizing on extant genetic data and longitudinal SBP assessments available through GAW19 to explore novel analytical methods with promising results