Deterministic, Stash-Free Write-Only ORAM

Write-Only Oblivious RAM (WoORAM) protocols provide privacy by encrypting the contents of data and also hiding the pattern of write operations over that data. WoORAMs provide better privacy than plain encryption and better performance than more general ORAM schemes (which hide both writing and reading access patterns), and the write-oblivious setting has been applied to important applications of cloud storage synchronization and encrypted hidden volumes. In this paper, we introduce an entirely new technique for Write-Only ORAM, called DetWoORAM. Unlike previous solutions, DetWoORAM uses a deterministic, sequential writing pattern without the need for any "stashing" of blocks in local state when writes fail. Our protocol, while conceptually simple, provides substantial improvement over prior solutions, both asymptotically and experimentally. In particular, under typical settings the DetWoORAM writes only 2 blocks (sequentially) to backend memory for each block written to the device, which is optimal. We have implemented our solution using the BUSE (block device in user-space) module and tested DetWoORAM against both an encryption only baseline of dm-crypt and prior, randomized WoORAM solutions, measuring only a 3x-14x slowdown compared to an encryption-only baseline and around 6x-19x speedup compared to prior work

Designing and implementing effective campus sustainability in Saudi Arabian universities: an assessment of drivers and barriers in a rational choice theoretical context

Saudi Arabia is a developing country that is experiencing a rapid growth in its population and level of urbanisation. Higher education (HE) in the country has developed rapidly over the last ten years, and it is still moving through numerous major reforms. Largely, the concept of sustainability has not yet been formally adopted in public institutions in a way that could sufficiently remedy the range of activities that currently impact negatively on the environment. The central aim of this paper is to examine the extent to which planning and action for sustainability is currently being taken on university campuses in Saudi Arabia, and to review the opportunities and challenges for encouraging and enabling further progress to this end. The research that the paper draws on specifically investigated the influence of decision makers’ personal knowledge and perceptions within Facilities and Project Management (FPM) departments at selected Saudi universities, and the constraints faced by FPM decision makers with regard to the promotion of sustainability on campus. This exploration was supported by the development of a theoretical framework that draws on rational choice theory (RCT). The research revealed mixed levels of prevailing knowledge and awareness towards sustainability among FPM decision makers within the case study university campuses. Cost notably came across as a dominant influence on FPM decision makers’ choices and decisions, and it undoubtedly plays an important role in shaping the decision-making process alongside other key organisational factors. A number of barriers facing the incorporation of sustainability emerged with clarity, such as the lack of supportive leadership, the lack of sustainability knowledge and awareness among senior management and an absence of sustainability-related legislation policy or strategic direction in the HEIs concerned

Tooth Decay in Alcohol Abusers Compared to Alcohol and Drug Abusers

Alcohol and drug abuse are detrimental to general and oral health. Though we know the effects of these harmful habits on oral mucosa, their independent and combined effect on the dental caries experience is unknown and worthy of investigation. We compared 363 “alcohol only” abusers to 300 “alcohol and drug” abusers to test the hypothesis that various components of their dental caries experience are significantly different due to plausible sociobiological explanations. After controlling for the potential confounders, we observe that the “alcohol and drug” group had a 38% higher risk of having decayed teeth compared to the “alcohol only” group (P < .05). As expected, those who belonged to a higher social class (OR = 1.98; 95%  CI = 1.43–2.75) and drank wine (OR = 1.85; 95%  CI = 1.16–2.96) had a higher risk of having more filled teeth. We conclude that the risk of tooth decay among “alcohol only” abusers is significantly lower compared to “alcohol and drug” abusers

De novo identification of differentially methylated regions in the human genome

Background: The identification and characterisation of differentially methylated regions (DMRs) between phenotypes in the human genome is of prime interest in epigenetics. We present a novel method, DMRcate, that fits replicated methylation measurements from the Illumina HM450K BeadChip (or 450K array) spatially across the genome using a Gaussian kernel. DMRcate identifies and ranks the most differentially methylated regions across the genome based on tunable kernel smoothing of the differential methylation (DM) signal. The method is agnostic to both genomic annotation and local change in the direction of the DM signal, removes the bias incurred from irregularly spaced methylation sites, and assigns significance to each DMR called via comparison to a null model. Results: We show that, for both simulated and real data, the predictive performance of DMRcate is superior to those of Bumphunter and Probe Lasso, and commensurate with that of comb-p. For the real data, we validate all array-derived DMRs from the candidate methods on a suite of DMRs derived from whole-genome bisulfite sequencing called from the same DNA samples, using two separate phenotype comparisons. Conclusions: The agglomeration of genomically localised individual methylation sites into discrete DMRs is currently best served by a combination of DM-signal smoothing and subsequent threshold specification. The findings also suggest the design of the 450K array shows preference for CpG sites that are more likely to be differentially methylated, but its overall coverage does not adequately reflect the depth and complexity of methylation signatures afforded by sequencing. For the convenience of the research community we have created a user-friendly R software package called DMRcate, downloadable from Bioconductor and compatible with existing preprocessing packages, which allows others to apply the same DMR-finding method on 450K array data

Coupling angle variability in healthy and patellofemoral pain runners

Background Patellofemoral pain is hypothesized to result in less joint coordination variability. The ability to relate coordination variability to patellofemoral pain pathology could have many clinical uses; however, evidence to support its clinical application is lacking. The aim was to determine if vector coding's coupling angle variability, as a measure of joint coordination variability, was less for runners with patellofemoral pain than healthy controls as is commonly postulated. Methods Nineteen female recreational runners with patellofemoral pain and eleven healthy controls performed a treadmill acclimation protocol then ran at a self-selected pace for 15 min. 3-D kinematics, force plate kinetics, knee pain and rating of perceived exertion were recorded each minute. Data were selected for the: pain group at the highest pain reached (pain � 3/10) in a non-exerted state (exertion < 14/20), and; non-exerted healthy group from the eleventh minute. Coupling angle variability was calculated over several portions of the stride for six knee-ankle combinations during five non-consecutive strides. Findings 46 of 48 coupling angle variability measures were greater for the pain group, with 7 significantly greater (P <.05). Interpretation These findings oppose the theory that less coupling angle variability is indicative of a pathological coordinate state during running. Greater coupling angle variability may be characteristic of patellofemoral pain in female treadmill running when a larger threshold of pain is reached than previously observed. A predictable and directional response of coupling angle variability measures in relation to knee pathology is not yet clear and requires further investigation prior to considerations for clinical utility. © 2013 Elsevier Ltd

MRCK-1 Drives Apical Constriction in C. elegans by Linking Developmental Patterning to Force Generation

Apical constriction is a change in cell shape that drives key morphogenetic events including gastrulation and neural tube formation. Apical force-producing actomyosin networks drive apical constriction by contracting while connected to cell-cell junctions. The mechanisms by which developmental patterning regulates these actomyosin networks and associated junctions with spatial precision are not fully understood. Here, we identify a myosin light chain kinase MRCK-1 as a key regulator of C. elegans gastrulation that integrates spatial and developmental patterning information. We show that MRCK-1 is required for activation of contractile actomyosin dynamics and elevated cortical tension in the apical cell cortex of endodermal precursor cells. MRCK-1 is apically localized by active Cdc42 at the external, cell-cell contact-free surfaces of apically constricting cells, downstream of cell fate determination mechanisms. We establish that the junctional components α-catenin, β-catenin, and cadherin become highly enriched at the apical junctions of apically-constricting cells, and that MRCK-1 and myosin activity are required in vivo for this enrichment. Taken together, our results define mechanisms that position a myosin activator to a specific cell surface where it both locally increases cortical tension and locally enriches junctional components to facilitate apical constriction. These results reveal crucial links that can tie spatial information to local force generation to drive morphogenesis

Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome

Abstract Objective: The aim of this study was to obtain comprehensive information on basal hypothalamic-pituitary-adrenal (HPA) axis activity in chronic fatigue syndrome (CFS) patients who were not affected by medication or comorbid psychiatric disorder likely to influence the HPA axis. Method: Steroid analysis of urine collections from 0600 to 2100 h at 3-h intervals in CFS patients and in controls. Results: Urinary free cortisol and cortisone concentrations showed a significant normal diurnal rhythm, but levels were lower across the cycle in CFS. In contrast, while urinary cortisol metabolites also showed a normal diurnal rhythm, levels were not significantly different between the CFS and controls at any time. Derived metabolite ratios were similar in both groups. Conclusion: This study provides further evidence for reduced basal HPA axis function in patients with CFS, based on lower free cortisol and cortisone levels, but this is not corroborated by cortisol metabolite data. The difference between these measures cannot be explained by an altered timing of the diurnal rhythm.

Diurnal excretion of urinary cortisol, cortisone, and cortisol metabolites in chronic fatigue syndrome

Abstract Objective: The aim of this study was to obtain comprehensive information on basal hypothalamic-pituitary-adrenal (HPA) axis activity in chronic fatigue syndrome (CFS) patients who were not affected by medication or comorbid psychiatric disorder likely to influence the HPA axis. Method: Steroid analysis of urine collections from 0600 to 2100 h at 3-h intervals in CFS patients and in controls. Results: Urinary free cortisol and cortisone concentrations showed a significant normal diurnal rhythm, but levels were lower across the cycle in CFS. In contrast, while urinary cortisol metabolites also showed a normal diurnal rhythm, levels were not significantly different between the CFS and controls at any time. Derived metabolite ratios were similar in both groups. Conclusion: This study provides further evidence for reduced basal HPA axis function in patients with CFS, based on lower free cortisol and cortisone levels, but this is not corroborated by cortisol metabolite data. The difference between these measures cannot be explained by an altered timing of the diurnal rhythm.

Population-Based Assessment of a Biomarker-Based Screening Pathway to Aid Diagnosis of Monogenic Diabetes in Young-Onset Patients

This is the author accepted manuscript. The final version is available from the American Diabetes Association via the DOI in this record.Objective: Monogenic diabetes, a young-onset form of diabetes, is often misdiagnosed as Type 1 diabetes, resulting in unnecessary treatment with insulin. A screening approach for monogenic diabetes is needed to accurately select suitable patients for expensive diagnostic genetic testing. We used C-peptide and islet autoantibodies, highly sensitive and specific biomarkers for discriminating Type 1 from non-Type 1 diabetes, in a biomarker screening pathway for monogenic diabetes. Research Design and Methods: We studied patients diagnosed ≤30y, currently <50y, in two UK regions with existing high detection of monogenic diabetes. The biomarker screening pathway comprised 3 stages: 1) Assessment of endogenous insulin secretion using urinary C-peptide/creatinine ratio (UCPCR); 2) If UCPCR≥0.2nmol/mmol, measurement of GAD and IA2 islet autoantibodies; 3) If negative for both autoantibodies, molecular genetic diagnostic testing for 35 monogenic diabetes subtypes. Results: 1407 patients participated (1365 no known genetic cause, 34 monogenic diabetes, 8 cystic-fibrosis-related diabetes). 386/1365(28%) had UCPCR≥0.2nmol/mmol. 216/386(56%) of these patients were negative for GAD and IA2 and underwent molecular genetic testing. 17 new cases of monogenic diabetes were diagnosed (8 common MODY (Sanger sequencing), 9 rarer causes (next generation sequencing)) in addition to the 34 known cases (estimated prevalence of 3.6% (51/1407) (95%CI: 2.7-4.7%)). The positive predictive value was 20%, suggesting a 1-in-5 detection rate for the pathway. The negative predictive value was 99.9%. Conclusions: The biomarker screening pathway for monogenic diabetes is an effective, cheap, and easily implemented approach to systematically screening all young-onset patients. The minimum prevalence of monogenic diabetes is 3.6% of patients diagnosed ≤30y.This study was funded by the Department of Health and Wellcome Trust Health Innovation Challenge Award (HICF-1009-041; WT-091985). ATH and SE are Wellcome Trust Senior Investigators. ATH is an NIHR Senior Investigator. BS, ATH, MH, SE, and BK are core members of the NIHR Exeter Clinical Research Facility. EP is a Wellcome Trust New Investigator. TM is supported by NIHR CSO Fellowship. JP is partly funded by the NIHR Collaboration for Leadership in Applied Health Research and Care for the South West (PenCLAHRC)

Comprehensive identification of essential Staphylococcus aureus genes using Transposon-Mediated Differential Hybridisation (TMDH).

BACKGROUND: In recent years there has been an increasing problem with Staphylococcus aureus strains that are resistant to treatment with existing antibiotics. An important starting point for the development of new antimicrobial drugs is the identification of "essential" genes that are important for bacterial survival and growth. RESULTS: We have developed a robust microarray and PCR-based method, Transposon-Mediated Differential Hybridisation (TMDH), that uses novel bioinformatics to identify transposon inserts in genome-wide libraries. Following a microarray-based screen, genes lacking transposon inserts are re-tested using a PCR and sequencing-based approach. We carried out a TMDH analysis of the S. aureus genome using a large random mariner transposon library of around a million mutants, and identified a total of 351 S. aureus genes important for survival and growth in culture. A comparison with the essential gene list experimentally derived for Bacillus subtilis highlighted interesting differences in both pathways and individual genes. CONCLUSION: We have determined the first comprehensive list of S. aureus essential genes. This should act as a useful starting point for the identification of potential targets for novel antimicrobial compounds. The TMDH methodology we have developed is generic and could be applied to identify essential genes in other bacterial pathogens.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are