Assembling networks of microbial genomes using linear programming

<p>Abstract</p> <p>Background</p> <p>Microbial genomes exhibit complex sets of genetic affinities due to lateral genetic transfer. Assessing the relative contributions of parent-to-offspring inheritance and gene sharing is a vital step in understanding the evolutionary origins and modern-day function of an organism, but recovering and showing these relationships is a challenging problem.</p> <p>Results</p> <p>We have developed a new approach that uses linear programming to find between-genome relationships, by treating tables of genetic affinities (here, represented by transformed BLAST e-values) as an optimization problem. Validation trials on simulated data demonstrate the effectiveness of the approach in recovering and representing vertical and lateral relationships among genomes. Application of the technique to a set comprising <it>Aquifex aeolicus </it>and 75 other thermophiles showed an important role for large genomes as 'hubs' in the gene sharing network, and suggested that genes are preferentially shared between organisms with similar optimal growth temperatures. We were also able to discover distinct and common genetic contributors to each sequenced representative of genus <it>Pseudomonas</it>.</p> <p>Conclusions</p> <p>The linear programming approach we have developed can serve as an effective inference tool in its own right, and can be an efficient first step in a more-intensive phylogenomic analysis.</p

An analysis of trends, frequencies and factors influencing the development of resistance to phosphine in the red flour beetle Tribolium castaneum (Herbst) in Australia

Although resistance to phosphine, the key disinfestant used worldwide in the stored grain environment has been an ongoing industry issue, studies on its trend over large geographic region and over long period of time is very limited. In this study, we critically analysed 20 years' phosphine resistance diagnosis data for the red flour beetle Tribolium castaneum (Herbst) stored in the Australian Grain Insect Resistance Database. Resistance diagnosis on a staggering 6336 samples, along with information on storage types and treatment history was interrogated to establish trends and frequencies of resistance development in this species and factors that may have contributed towards these resistance occurences. Using descriptive statistics, linear and trend analysis and a well established Bayesian hurdle model, we determined that strong resistance in T. castaneum was significantly more prevalent in quarantine intereceptions than in central storages and on farms. The strong resistance incidences had been confined to eastern states of Queensland, New South Wales, Victoria and South Australia, whereas it is yet to be detected in the state of Western Australia. We could not establish any significant correlation between the strong resistance development and any commodity or treatments. After an initial increasing trend in incidences since the first detection of strong resistance in 1997 in this species, the frequency was stabilised during 2001–08; after which there had been an upward trend since 2009 till the last survey in 2013. The conclusions derived from this analyses highlighted the importance of a resistance monitoring program with relevant information being used in Australia as the basis for ongoing and future phosphine resistance management strategies. This research may also proved valuable towards devising similar strategies in overseas countries with phosphine resistance problems

Statistical mechanics of Fofonoff flows in an oceanic basin

We study the minimization of potential enstrophy at fixed circulation and energy in an oceanic basin with arbitrary topography. For illustration, we consider a rectangular basin and a linear topography h=by which represents either a real bottom topography or the beta-effect appropriate to oceanic situations. Our minimum enstrophy principle is motivated by different arguments of statistical mechanics reviewed in the article. It leads to steady states of the quasigeostrophic (QG) equations characterized by a linear relationship between potential vorticity q and stream function psi. For low values of the energy, we recover Fofonoff flows [J. Mar. Res. 13, 254 (1954)] that display a strong westward jet. For large values of the energy, we obtain geometry induced phase transitions between monopoles and dipoles similar to those found by Chavanis and Sommeria [J. Fluid Mech. 314, 267 (1996)] in the absence of topography. In the presence of topography, we recover and confirm the results obtained by Venaille and Bouchet [Phys. Rev. Lett. 102, 104501 (2009)] using a different formalism. In addition, we introduce relaxation equations towards minimum potential enstrophy states and perform numerical simulations to illustrate the phase transitions in a rectangular oceanic basin with linear topography (or beta-effect).Comment: 26 pages, 28 figure

Electron exchange coupling in a naturally occurring tetramangano cluster in the mineral helvite, (Mn4S)(SiBeO4)3

The mineral helvite, (Mn4S)(BeSiO4)3, contains discrete tetrahedral Mn4S+6 clusters in which the S-2 is tetrahedrally coordinated and each Mn(II) is in a distorted tetrahedron of one S-2 and three oxygens; the cluster is situated within an encompassing lattice of SiO4-4 and BeO4-6 tetrahedra. Mn4S+6 centers provide an interesting model for comparison to the polynuclear manganese center that is associated with photosynthetic water oxidation. Magnetic susceptibility data between 77 and 298 K have been measured for a natural helvite sample containing principally Mn4S+6 centers but with significant contamination from Mn3FeS+6 and Mn3CaS+6. The data exhibited Curie-Weiss behavior with [mu]eff = 5.969 B.M. and [theta] = 178.3 K. An analysis of the magnetic susceptibility, based on Van Vleck's formalism, demonstrated the presence of antiferromagnetic coupling, with a coupling constant J = -5.83 cm-1. Mossbauer spectra of Mn3FeS centers in helvite and of Fe4S centers in the related mineral danalite have also been recorded. Isomer shifts show little temperature dependence and lie in the range 1.23-1.43 mm/sec.. This range is typical of tetrahedrally coordinated Fe(II) in several ionic crystals but is significantly above that of Fe(II) in ferredoxins and below that in the [quinone-Fe(II)-quinone] complex of the photosynthetic bacterium,Rhodopseudomonas sphaeroides. Quadrupole splittings are highly temperature dependent, ranging from 2.4 mm/sec at 4.2 K to less than 0.5 mm/sec at 248 K.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25645/1/0000197.pd

Ethics of sham surgery: Perspective of patients

Sham surgery is used as a control condition in neurosurgical clinical trials in Parkinson's disease (PD) but remains controversial. This study aimed to assess the perspective of patients with PD and the general public on the use of sham surgery controls. We surveyed consecutive patients from a university-based neurology outpatient clinic and a community-based general internal medicine practice. Background information was provided regarding PD and two possible methods of testing the efficacy of a novel gene transfer procedure, followed by questions that addressed participants' opinions related to the willingness to participate and permissibility of blinded and unblinded trial designs. Two hundred eighty-eight (57.6%) patients returned surveys. Patients with PD expressed less willingness to participate in the proposed gene transfer surgery trials. Unblinded studies received greater support, but a majority would still allow the use of sham surgery. Those in favor of sham surgery were more educated and more likely to use societal perspective rationales. Patients with PD are more cautious about surgical research participation than patients with non-PD. Their policy views were similar to others', with a majority supporting the use of sham controls. Future research needs to determine whether eliciting more considered judgments of laypersons would reveal different levels of support for sham surgery. © 2007 Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57916/1/21775_ftp.pd

Sham surgery controls in Parkinson's disease clinical trials: Views of participants

Background: Sham surgery controls are increasingly used in neurosurgical clinical trials in Parkinson's disease (PD) but remain controversial. We interviewed participants of such trials, specifically examining their understanding and attitudes regarding sham surgery. Methods: We conducted semistructured qualitative interviews with participants of 3 sham surgery–controlled trials for PD, focusing on their understanding of sham design, their reactions to it, its impact on decision making, and their understanding of posttrial availability of the experimental intervention and its impact on decisions to participate. Results: All subjects (n = 90) understood the 2‐arm design; most (86%) described the procedural differences between the arms accurately. Ninety‐two percent referred to scientific or regulatory reasons as rationales for the sham control, with 62% specifically referring to the placebo effect. Ninety‐one percent said posttrial availability of the experimental intervention had a strong (48%) or some (43%) influence on their decision to participate, but only 68% understood the conditions for posttrial availability. Conclusions: Most subjects in sham surgery–controlled PD trials comprehend the sham surgery design and its rationale. Although there is room for improvement, most subjects of sham surgery trials appear to be adequately informed. © 2012 Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93771/1/25155_ftp.pd

Circadian patterns of Wikipedia editorial activity: A demographic analysis

Wikipedia (WP) as a collaborative, dynamical system of humans is an appropriate subject of social studies. Each single action of the members of this society, i.e. editors, is well recorded and accessible. Using the cumulative data of 34 Wikipedias in different languages, we try to characterize and find the universalities and differences in temporal activity patterns of editors. Based on this data, we estimate the geographical distribution of editors for each WP in the globe. Furthermore we also clarify the differences among different groups of WPs, which originate in the variance of cultural and social features of the communities of editors

Source Attribution and Interannual Variability of Arctic Pollution in Spring Constrained by Aircraft (ARCTAS, ARCPAC) and Satellite (AIRS) Observations of Carbon Monoxide

We use aircraft observations of carbon monoxide (CO) from the NASA ARCTAS and NOAA ARCPAC campaigns in April 2008 together with multiyear (2003–2008) CO satellite data from the AIRS instrument and a global chemical transport model (GEOS-Chem) to better understand the sources, transport, and interannual variability of pollution in the Arctic in spring. Model simulation of the aircraft data gives best estimates of CO emissions in April 2008 of $26 Tg month^{−1}$ for Asian anthropogenic, 9.4 for European anthropogenic, 4.1 for North American anthropogenic, 15 for Russian biomass burning (anomalously large that year), and 23 for Southeast Asian biomass burning. We find that Asian anthropogenic emissions are the dominant source of Arctic CO pollution everywhere except in surface air where European anthropogenic emissions are of similar importance. Russian biomass burning makes little contribution to mean CO (reflecting the long CO lifetime) but makes a large contribution to CO variability in the form of combustion plumes. Analysis of two pollution events sampled by the aircraft demonstrates that AIRS can successfully observe pollution transport to the Arctic in the mid-troposphere. The 2003–2008 record of CO from AIRS shows that interannual variability averaged over the Arctic cap is very small. AIRS CO columns over Alaska are highly correlated with the Ocean Niño Index, suggesting a link between El Niño and Asian pollution transport to the Arctic. AIRS shows lower-than-average CO columns over Alaska during April 2008, despite the Russian fires, due to a weakened Aleutian Low hindering transport from Asia and associated with the moderate 2007–2008 La Niña. This suggests that Asian pollution influence over the Arctic may be particularly large under strong El Niño conditions.Engineering and Applied Science

Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, double-blind, placebo-controlled, phase 3 trial

Background: Rucaparib, a poly(ADP-ribose) polymerase inhibitor, has anticancer activity in recurrent ovarian carcinoma harbouring a BRCA mutation or high percentage of genome-wide loss of heterozygosity. In this trial we assessed rucaparib versus placebo after response to second-line or later platinum-based chemotherapy in patients with high-grade, recurrent, platinum-sensitive ovarian carcinoma. Methods: In this randomised, double-blind, placebo-controlled, phase 3 trial, we recruited patients from 87 hospitals and cancer centres across 11 countries. Eligible patients were aged 18 years or older, had a platinum-sensitive, high-grade serous or endometrioid ovarian, primary peritoneal, or fallopian tube carcinoma, had received at least two previous platinum-based chemotherapy regimens, had achieved complete or partial response to their last platinum-based regimen, had a cancer antigen 125 concentration of less than the upper limit of normal, had a performance status of 0–1, and had adequate organ function. Patients were ineligible if they had symptomatic or untreated central nervous system metastases, had received anticancer therapy 14 days or fewer before starting the study, or had received previous treatment with a poly(ADP-ribose) polymerase inhibitor. We randomly allocated patients 2:1 to receive oral rucaparib 600 mg twice daily or placebo in 28 day cycles using a computer-generated sequence (block size of six, stratified by homologous recombination repair gene mutation status, progression-free interval after the penultimate platinum-based regimen, and best response to the most recent platinum-based regimen). Patients, investigators, site staff, assessors, and the funder were masked to assignments. The primary outcome was investigator-assessed progression-free survival evaluated with use of an ordered step-down procedure for three nested cohorts: patients with BRCA mutations (carcinoma associated with deleterious germline or somatic BRCA mutations), patients with homologous recombination deficiencies (BRCA mutant or BRCA wild-type and high loss of heterozygosity), and the intention-to-treat population, assessed at screening and every 12 weeks thereafter. This trial is registered with ClinicalTrials.gov, number NCT01968213; enrolment is complete. Findings: Between April 7, 2014, and July 19, 2016, we randomly allocated 564 patients: 375 (66%) to rucaparib and 189 (34%) to placebo. Median progression-free survival in patients with a BRCA-mutant carcinoma was 16·6 months (95% CI 13·4–22·9; 130 [35%] patients) in the rucaparib group versus 5·4 months (3·4–6·7; 66 [35%] patients) in the placebo group (hazard ratio 0·23 [95% CI 0·16–0·34]; p&lt;0·0001). In patients with a homologous recombination deficient carcinoma (236 [63%] vs 118 [62%]), it was 13·6 months (10·9–16·2) versus 5·4 months (5·1–5·6; 0·32 [0·24–0·42]; p&lt;0·0001). In the intention-to-treat population, it was 10·8 months (8·3–11·4) versus 5·4 months (5·3–5·5; 0·36 [0·30–0·45]; p&lt;0·0001). Treatment-emergent adverse events of grade 3 or higher in the safety population (372 [99%] patients in the rucaparib group vs 189 [100%] in the placebo group) were reported in 209 (56%) patients in the rucaparib group versus 28 (15%) in the placebo group, the most common of which were anaemia or decreased haemoglobin concentration (70 [19%] vs one [1%]) and increased alanine or aspartate aminotransferase concentration (39 [10%] vs none). Interpretation: Across all primary analysis groups, rucaparib significantly improved progression-free survival in patients with platinum-sensitive ovarian cancer who had achieved a response to platinum-based chemotherapy. ARIEL3 provides further evidence that use of a poly(ADP-ribose) polymerase inhibitor in the maintenance treatment setting versus placebo could be considered a new standard of care for women with platinum-sensitive ovarian cancer following a complete or partial response to second-line or later platinum-based chemotherapy. Funding: Clovis Oncology