Verification of PCP-Related Computational Reductions in Coq

We formally verify several computational reductions concerning the Post correspondence problem (PCP) using the proof assistant Coq. Our verifications include a reduction of a string rewriting problem generalising the halting problem for Turing machines to PCP, and reductions of PCP to the intersection problem and the palindrome problem for context-free grammars. Interestingly, rigorous correctness proofs for some of the reductions are missing in the literature

Temporal variability of nitrogen fixation and particulate nitrogen export at Station ALOHA

We present nearly 9 yrs (June 2005–December 2013) of measurements of upper‐ocean (0 m to 125 m) dinitrogen (N2) fixation rates, coupled with particulate nitrogen (PN) export at 150 m, from Station ALOHA (22° 45′N, 158°W) in the North Pacific Subtropical Gyre. Between June 2005 and June 2012, N2 fixation rates were measured based on adding the 15N2 tracer as a gas bubble. Beginning in August 2012, 15N2 was first dissolved into filtered seawater and the 15N2‐enriched water was subsequently added to N2 fixation incubations. Direct comparisons between methodologies revealed a robust relationship, with the addition of 15N2‐enriched seawater resulting in twofold greater depth‐integrated rates than those derived from adding a 15N2 gas bubble. Based on this relationship, we corrected the initial period of measurements, and the resulting rates of N2 fixation averaged 230 ± 136 μmol N m−2 d−1 for the full time series (n = 71). Analysis of the 15N isotopic composition of sinking PN, together with an isotope mass balance model, revealed that N2 fixation supported 26–47% of PN export during calendar years 2006–2013. The N export derived from these fractional contributions and measured N2 fixation rates ranged between 502 and 919 μmol N m−2 d−1, which are equivalent to rates of net community production (NCP) of 1.5 to 2.7 mol C m−2 yr−1, consistent with previous independent estimates of NCP at this site

Rosetta Brains: A Strategy for Molecularly-Annotated Connectomics

We propose a neural connectomics strategy called Fluorescent In-Situ Sequencing of Barcoded Individual Neuronal Connections (FISSEQ-BOINC), leveraging fluorescent in situ nucleic acid sequencing in fixed tissue (FISSEQ). FISSEQ-BOINC exhibits different properties from BOINC, which relies on bulk nucleic acid sequencing. FISSEQ-BOINC could become a scalable approach for mapping whole-mammalian-brain connectomes with rich molecular annotations

Patient-maintained sedation for oral surgery using a target-controlled infusion of propofol - a pilot study

OBJECTIVE: To assess the safety and efficacy of a new patient-maintained propofol system for conscious sedation in dentistry. DESIGN: Prospective clinical trial SETTING: Department of Sedation, Glasgow Dental Hospital and School, 2001 SUBJECTS AND METHODS: Patients scheduled for oral surgery with conscious sedation. Exclusions included ASA IV -V, inability to use the handset, opioid use and severe respiratory disease. INTERVENTIONS: Patients were given intravenous propofol to a level of 1.0 microg/ml (reducing from 1.5 microg/ml) using a target controlled infusion system, they then controlled their sedation level by double-clicking a handset which on each activation increased the propofol concentration by 0.2 microg/ml. MAIN OUTCOME MEASURES: Oxygen saturation, patient satisfaction, and surgeon satisfaction. RESULTS: Twenty patients were recruited, 16 female and four male. Nineteen patients completed sedation and treatment successfully. Mean lowest oxygen saturation was 94%. No patients were over-sedated. All patients successfully used the system to maintain a level of sedation adequate for their comfort. Patient and surgeon satisfaction were consistently high. CONCLUSIONS: Initial experience with this novel system has confirmed safety, patient satisfaction and surgeon satisfaction

Hippocrates revisited? Old ideals and new realities

Individual genomics has arrived, personal decisions to make use of it are a new reality. What are the implications for the patient–physician relationship? In this article we address three factors that call the traditional concept of confidentiality into question. First, the illusion of absolute data safety, as shown by medical informatics. Second, data sharing as a standard practice in genomics research. Comprehensive data sets are widely accessible. Third, genotyping has become a service that is directly available to consumers. The availability and accessibility of personal health data strongly suggest that the roles in the clinical encounter need to be remodeled. The old ideal of physicians as keepers of confidential information is outstripped by the reality of individuals who decide themselves about the way of using their data

Targeted and Genome-Scale Methylomics Reveals Gene Body Signatures in Human Cell Lines

Cytosine methylation, an epigenetic modification of DNA, is a target of growing interest for developing high throughput profiling technologies. Here we introduce two new, complementary techniques for cytosine methylation profiling utilizing next generation sequencing technology: bisulfite padlock probes (BSPPs) and methyl sensitive cut counting (MSCC). In the first method, we designed a set of ~10,000 BSPPs distributed over the ENCODE pilot project regions to take advantage of existing expression and chromatin immunoprecipitation data. We observed a pattern of low promoter methylation coupled with high gene body methylation in highly expressed genes. Using the second method, MSCC, we gathered genome-scale data for 1.4 million HpaII sites and confirmed that gene body methylation in highly expressed genes is a consistent phenomenon over the entire genome. Our observations highlight the usefulness of techniques which are not inherently or intentionally biased in favor of only profiling particular subsets like CpG islands or promoter regions

Associations between Cardiorespiratory Fitness and Health-Related Quality of Life

© 2009 Sloan et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Changes in Weight, Waist Circumference and Compensatory Responses with Different Doses of Exercise among Sedentary, Overweight Postmenopausal Women

It has been suggested that exercise training results in compensatory mechanisms that attenuate weight loss. However, this has only been examined with large doses of exercise. The goal of this analysis was to examine actual weight loss compared to predicted weight loss (compensation) across different doses of exercise in a controlled trial of sedentary, overweight or obese postmenopausal women (n = 411).Participants were randomized to a non-exercise control (n = 94) or 1 of 3 exercise groups; exercise energy expenditure of 4 (n = 139), 8 (n = 85), or 12 (n = 93) kcal/kg/week (KKW). Training intensity was set at the heart rate associated with 50% of each woman's peak VO(2) and the intervention period was 6 months. All exercise was supervised. The main outcomes were actual weight loss, predicted weight loss (exercise energy expenditure/ 7700 kcal per kg), compensation (actual minus predicted weight loss) and waist circumference. The study sample had a mean (SD) age 57.2 (6.3) years, BMI of 31.7 (3.8) kg/m(2), and was 63.5% Caucasian. The adherence to the intervention was >99% in all exercise groups. The mean (95% CI) weight loss in the 4, 8 and 12 KKW groups was -1.4 (-2.0, -0.8), -2.1 (-2.9, -1.4) and -1.5 (-2.2, -0.8) kg, respectively. In the 4 and 8 KKW groups the actual weight loss closely matched the predicted weight loss of -1.0 and -2.0 kg, respectively, resulting in no significant compensation. In the 12 KKW group the actual weight loss was less than the predicted weight loss (-2.7 kg) resulting in 1.2 (0.5, 1.9) kg of compensation (P<0.05 compared to 4 and 8 KKW groups). All exercise groups had a significant reduction in waist circumference which was independent of changes in weight.In this study of previously sedentary, overweight or obese, postmenopausal women we observed no difference in the actual and predicted weight loss with 4 and 8 KKW of exercise (72 and 136 minutes respectively), while the 12 KKW (194 minutes) produced only about half of the predicted weight loss. However, all exercise groups had a significant reduction in waist circumference which was independent of changes in weight.(ClinicalTrials.gov) NCT00011193

Improved annotation of 3' untranslated regions and complex loci by combination of strand-specific direct RNA sequencing, RNA-seq and ESTs

The reference annotations made for a genome sequence provide the framework for all subsequent analyses of the genome. Correct annotation is particularly important when interpreting the results of RNA-seq experiments where short sequence reads are mapped against the genome and assigned to genes according to the annotation. Inconsistencies in annotations between the reference and the experimental system can lead to incorrect interpretation of the effect on RNA expression of an experimental treatment or mutation in the system under study. Until recently, the genome-wide annotation of 3-prime untranslated regions received less attention than coding regions and the delineation of intron/exon boundaries. In this paper, data produced for samples in Human, Chicken and A. thaliana by the novel single-molecule, strand-specific, Direct RNA Sequencing technology from Helicos Biosciences which locates 3-prime polyadenylation sites to within +/- 2 nt, were combined with archival EST and RNA-Seq data. Nine examples are illustrated where this combination of data allowed: (1) gene and 3-prime UTR re-annotation (including extension of one 3-prime UTR by 5.9 kb); (2) disentangling of gene expression in complex regions; (3) clearer interpretation of small RNA expression and (4) identification of novel genes. While the specific examples displayed here may become obsolete as genome sequences and their annotations are refined, the principles laid out in this paper will be of general use both to those annotating genomes and those seeking to interpret existing publically available annotations in the context of their own experimental dataComment: 44 pages, 9 figure