Interpolative multidimensional scaling techniques for the identification of clusters in very large sequence sets

<p>Abstract</p> <p>Background</p> <p>Modern pyrosequencing techniques make it possible to study complex bacterial populations, such as <it>16S rRNA</it>, directly from environmental or clinical samples without the need for laboratory purification. Alignment of sequences across the resultant large data sets (100,000+ sequences) is of particular interest for the purpose of identifying potential gene clusters and families, but such analysis represents a daunting computational task. The aim of this work is the development of an efficient pipeline for the clustering of large sequence read sets.</p> <p>Methods</p> <p>Pairwise alignment techniques are used here to calculate genetic distances between sequence pairs. These methods are pleasingly parallel and have been shown to more accurately reflect accurate genetic distances in highly variable regions of <it>rRNA </it>genes than do traditional multiple sequence alignment (MSA) approaches. By utilizing Needleman-Wunsch (NW) pairwise alignment in conjunction with novel implementations of interpolative multidimensional scaling (MDS), we have developed an effective method for visualizing massive biosequence data sets and quickly identifying potential gene clusters.</p> <p>Results</p> <p>This study demonstrates the use of interpolative MDS to obtain clustering results that are qualitatively similar to those obtained through full MDS, but with substantial cost savings. In particular, the wall clock time required to cluster a set of 100,000 sequences has been reduced from seven hours to less than one hour through the use of interpolative MDS.</p> <p>Conclusions</p> <p>Although work remains to be done in selecting the optimal training set size for interpolative MDS, substantial computational cost savings will allow us to cluster much larger sequence sets in the future.</p

TADPOL: A 1.3 mm Survey of Dust Polarization in Star-forming Cores and Regions

We present {\lambda}1.3 mm CARMA observations of dust polarization toward 30 star-forming cores and 8 star-forming regions from the TADPOL survey. We show maps of all sources, and compare the ~2.5" resolution TADPOL maps with ~20" resolution polarization maps from single-dish submillimeter telescopes. Here we do not attempt to interpret the detailed B-field morphology of each object. Rather, we use average B-field orientations to derive conclusions in a statistical sense from the ensemble of sources, bearing in mind that these average orientations can be quite uncertain. We discuss three main findings: (1) A subset of the sources have consistent magnetic field (B-field) orientations between large (~20") and small (~2.5") scales. Those same sources also tend to have higher fractional polarizations than the sources with inconsistent large-to-small-scale fields. We interpret this to mean that in at least some cases B-fields play a role in regulating the infall of material all the way down to the ~1000 AU scales of protostellar envelopes. (2) Outflows appear to be randomly aligned with B-fields; although, in sources with low polarization fractions there is a hint that outflows are preferentially perpendicular to small-scale B-fields, which suggests that in these sources the fields have been wrapped up by envelope rotation. (3) Finally, even at ~2.5" resolution we see the so-called "polarization hole" effect, where the fractional polarization drops significantly near the total intensity peak. All data are publicly available in the electronic edition of this article.Comment: 53 pages, 37 figures -- main body (13 pp., 3 figures), source maps (32 pp., 34 figures), source descriptions (8 pp.). Accepted by the Astrophysical Journal Supplemen

Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders

Background Cerebral palsy (CP) is an heterogeneous group of neurological disorders of movement and/or posture, with an estimated incidence of 1 in 1000 live births. Non-progressive forms of symmetrical, spastic CP have been identified, which show a Mendelian autosomal recessive pattern of inheritance. We recently described the mapping of a recessive spastic CP locus to a 5 cM chromosomal region located at 2q24-31.1, in rare consanguineous families. Methods Here we present data that refine this locus to a 0.5 cM region, flanked by the microsatellite markers D2S2345 and D2S326. The minimal region contains the candidate gene GAD1, which encodes a glutamate decarboxylase isoform (GAD67), involved in conversion of the amino acid and excitatory neurotransmitter glutamate to the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Results A novel amino acid mis-sense mutation in GAD67 was detected, which segregated with CP in affected individuals. Conclusions This result is interesting because auto-antibodies to GAD67 and the more widely studied GAD65 homologue encoded by the GAD2 gene, are described in patients with Stiff-Person Syndrome (SPS), epilepsy, cerebellar ataxia and Batten disease. Further investigation seems merited of the possibility that variation in the GAD1 sequence, potentially affecting glutamate/GABA ratios, may underlie this form of spastic CP, given the presence of anti-GAD antibodies in SPS and the recognised excitotoxicity of glutamate in various contexts

Submillimeter Array Observations of the RX J1633.9-2442 Transition Disk: Evidence for Multiple Planets in the Making

We present continuum high resolution Submillimeter Array (SMA) observations of the transition disk object RX J1633.9-2442, which is located in the Ophiuchus molecular cloud and has recently been identified as a likely site of ongoing giant planet formation. The observations were taken at 340 GHz (880 micron) with the SMA in its most extended configuration, resulting in an angular resolution of 0.3" (35 AU at the distance of the target). We find that the disk is highly inclined (i ~50 deg) and has an inner cavity ~25 AU in radius, which is clearly resolved by our observations. We simultaneously model the entire optical to millimeter wavelength spectral energy distribution (SED) and SMA visibilities of RX J1633.9-2442 in order to constrain the structure of its disk. We find that an empty cavity ~25 AU in radius is inconsistent with the excess emission observed at 12, 22, and 24 micron. Instead, the mid-IR excess can be modeled by either a narrow, optically thick ring at ~10 AU or an optically thin region extending from ~7 AU to ~25 AU. The inner disk (r < 5 AU) is mostly depleted of small dust grains as attested by the lack of detectable near-IR excess. We also present deep Keck aperture masking observations in the near-IR, which rule out the presence of a companion up to 500 times fainter than the primary star (in K-band) for projected separations in the 5-20 AU range. We argue that the complex structure of the RX J1633.9-2442 disk is best explained by multiple planets embedded within the disk. We also suggest that the properties and incidence of objects such as RX J1633.9-2442, T Cha, and LkCa 15 (and those of the companions recently identified to these two latter objects) are most consistent with the runaway gas accretion phase of the core accretion model, when giant planets gain their envelopes and suddenly become massive enough to open wide gaps in the disk.Comment: Accepted for publication in Ap

Communication style and exercise compliance in physiotherapy (CONNECT). A cluster randomized controlled trial to test a theory-based intervention to increase chronic low back pain patients’ adherence to physiotherapists’ recommendations: study rationale, design, and methods

Physical activity and exercise therapy are among the accepted clinical rehabilitation guidelines and are recommended self-management strategies for chronic low back pain. However, many back pain sufferers do not adhere to their physiotherapist’s recommendations. Poor patient adherence may decrease the effectiveness of advice and home-based rehabilitation exercises. According to self-determination theory, support from health care practitioners can promote patients’ autonomous motivation and greater long-term behavioral persistence (e.g., adherence to physiotherapists’ recommendations). The aim of this trial is to assess the effect of an intervention designed to increase physiotherapists’ autonomy-supportive communication on low back pain patients’ adherence to physical activity and exercise therapy recommendations. \ud \ud This study will be a single-blinded cluster randomized controlled trial. Outpatient physiotherapy centers (N =12) in Dublin, Ireland (population = 1.25 million) will be randomly assigned using a computer-generated algorithm to either the experimental or control arm. Physiotherapists in the experimental arm (two hospitals and four primary care clinics) will attend eight hours of communication skills training. Training will include handouts, workbooks, video examples, role-play, and discussion designed to teach physiotherapists how to communicate in a manner that promotes autonomous patient motivation. Physiotherapists in the waitlist control arm (two hospitals and four primary care clinics) will not receive this training. Participants (N = 292) with chronic low back pain will complete assessments at baseline, as well as 1 week, 4 weeks, 12 weeks, and 24 weeks after their first physiotherapy appointment. Primary outcomes will include adherence to physiotherapy recommendations, as well as low back pain, function, and well-being. Participants will be blinded to treatment allocation, as they will not be told if their physiotherapist has received the communication skills training. Outcome assessors will also be blinded. \ud \ud We will use linear mixed modeling to test between arm differences both in the mean levels and the rates of change of the outcome variables. We will employ structural equation modeling to examine the process of change, including hypothesized mediation effects. \ud \ud This trial will be the first to test the effect of a self-determination theory-based communication skills training program for physiotherapists on their low back pain patients’ adherence to rehabilitation recommendations. Current Controlled Trials ISRCTN63723433\u

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

The use of cessation assistance among smokers from China: Findings from the ITC China Survey

<p>Abstract</p> <p>Background</p> <p>Stop smoking medications significantly increase the likelihood of smoking cessation. However, there are no population-based studies of stop-smoking medication use in China, the largest tobacco market in the world. This study examined stop-smoking medication use and its association with quitting behavior among a population-based sample of Chinese smokers.</p> <p>Methods</p> <p>Face-to-face interviews were conducted with 4,627 smokers from six cities in the ITC China cohort survey. Longitudinal analyses were conducted using Wave 1 (April to August, 2006) and Wave 2 (November 2007 to January 2008).</p> <p>Results</p> <p>Approximately 26% of smokers had attempted to quit between Waves 1 and 2, and 6% were abstinent at 18-month follow-up. Only 5.8% of those attempting to quit reported NRT use and NRT was associated with lower odds of abstinence at Wave 2 (OR = 0.11; 95%CI = 0.03-0.46). Visiting a doctor/health professional was associated with greater attempts to quit smoking (OR = 1.60 and 2.78; 95%CI = 1.22-2.10 and 2.21-3.49 respectively) and being abstinent (OR = 1.77 and 1.85; 95%CI = 1.18-2.66 and 1.13-3.04 respectively) at 18-month follow-up relative to the smokers who did not visit doctor/health professional.</p> <p>Conclusions</p> <p>The use of formal help for smoking cessation is low in China. There is an urgent need to explore the use and effectiveness of stop-smoking medications in China and in other non-Western markets.</p