Beyond Nanopore Sequencing in Space: Identifying the Unknown

Astronaut Kate Rubins sequenced DNA on the International Space Station (ISS) for the first time in August 2016 (Figure 1A). A 2D sequencing library containing an equal mixture of lambda bacteriophage, Escherichia coli, and Mus musculus was prepared on the ground with a SQK_MAP006 kit and sent to the ISS frozen and loaded into R7.3 flow cells. After a total of 9 on-orbit sequencing runs over 6 months, it was determined that there was no decrease in sequencing performance on-orbit compared to ground controls (1). A total of ~280,000 and ~130,000 reads generated on-orbit and on the ground, respectively, identified 90% of reads that were attributed to 30% lambda bacteriophage, 30% Escherichia coli, and 30% M. musculus (Figure 1B). Extensive bioinformatics analysis determined comparable 2D and 1D read accuracies between flight and ground runs (Figure 1C), and data collected from the ISS were able to construct directed assemblies of E.coli and lambda genomes at 100% and M. musculus mitochondrial genome at 96.7%. These findings validate sequencing as a viable option for potential on-orbit applications such as environmental microbial monitoring and disease diagnosis. Current microbial monitoring of the ISS applies culture-based techniques that provide colony forming unit (CFU) data for air, water, and surface samples. The identity of the cultured microorganisms in unknown until sample return and ground-based analysis, a process that can take up to 60 days. For sequencing to benefit ISS applications, spaceflight-compatible sample preparation techniques are required. Subsequent to the testing of the MinION on-orbit, a sample-to-sequence method was developed using miniPCR and basic pipetting, which was only recently proven to be effective in microgravity. The work presented here details the in- flight sample preparation process and the first application of DNA sequencing on the ISS to identify unknown ISS-derived microorganisms

Beyond Nanopore Sequencing in Space: Identifying the Unknown

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Relationship between FEV1 change and patient-reported outcomes in randomised trials of inhaled bronchodilators for stable COPD: a systematic review.

BACKGROUND: Interactions between spirometry and patient-reported outcomes in COPD are not well understood. This systematic review and study-level analysis investigated the relationship between changes in FEV1 and changes in health status with bronchodilator therapy. METHODS: Six databases (to October 2009) were searched to identify studies with long-acting bronchodilator therapy reporting FEV1 and health status, dyspnoea or exacerbations. Mean and standard deviations of treatment effects were extracted for each arm of each study. Relationships between changes in trough FEV1 and outcomes were assessed using correlations and random-effects regression modelling. The primary outcome was St George's Respiratory Questionnaire (SGRQ) total score. RESULTS: Thirty-six studies (≥ 3 months) were included. Twenty-two studies (23,654 patients) with 49 treatment arms each contributing one data point provided SGRQ data. Change in trough FEV1 and change in SGRQ total score were negatively correlated (r = -0.46, p < 0.001); greater increases in FEV1 were associated with greater reductions (improvements) in SGRQ. The correlation strengthened with increasing study duration from 3 to 12 months. Regression modelling indicated that 100 mL increase in FEV1 (change at which patients are more likely to report improvement) was associated with a statistically significant reduction in SGRQ of 2.5 (95% CI 1.9, 3.1), while a clinically relevant SGRQ change (4.0) was associated with 160.6 (95% CI 129.0, 211.6) mL increase in FEV1. The association between change in FEV1 and other patient-reported outcomes was generally weak. CONCLUSIONS: Our analyses indicate, at a study level, that improvement in mean trough FEV1 is associated with proportional improvements in health status

Discovery and Follow-up Observations of the Young Type Ia Supernova 2016coj

The Type~Ia supernova (SN~Ia) 2016coj in NGC 4125 (redshift $z=0.004523$) was discovered by the Lick Observatory Supernova Search 4.9 days after the fitted first-light time (FFLT; 11.1 days before $B$-band maximum). Our first detection (pre-discovery) is merely $0.6\pm0.5$ day after the FFLT, making SN 2016coj one of the earliest known detections of a SN Ia. A spectrum was taken only 3.7 hr after discovery (5.0 days after the FFLT) and classified as a normal SN Ia. We performed high-quality photometry, low- and high-resolution spectroscopy, and spectropolarimetry, finding that SN 2016coj is a spectroscopically normal SN Ia, but with a high velocity of \ion{Si}{2} $\lambda$6355 ($\sim 12,600$\,\kms\ around peak brightness). The \ion{Si}{2} $\lambda$6355 velocity evolution can be well fit by a broken-power-law function for up to a month after the FFLT. SN 2016coj has a normal peak luminosity ($M_B \approx -18.9 \pm 0.2$ mag), and it reaches a $B$-band maximum \about16.0~d after the FFLT. We estimate there to be low host-galaxy extinction based on the absence of Na~I~D absorption lines in our low- and high-resolution spectra. The spectropolarimetric data exhibit weak polarization in the continuum, but the \ion{Si}{2} line polarization is quite strong ($\sim 0.9\% \pm 0.1\%$) at peak brightness.Comment: Submitte

Biomolecule Sequencer: Next-Generation DNA Sequencing Technology for In-Flight Environmental Monitoring, Research, and Beyond

On the International Space Station (ISS), technologies capable of rapid microbial identification and disease diagnostics are not currently available. NASA still relies upon sample return for comprehensive, molecular-based sample characterization. Next-generation DNA sequencing is a powerful approach for identifying microorganisms in air, water, and surfaces onboard spacecraft. The Biomolecule Sequencer payload, manifested to SpaceX-9 and scheduled on the Increment 4748 research plan (June 2016), will assess the functionality of a commercially-available next-generation DNA sequencer in the microgravity environment of ISS. The MinION device from Oxford Nanopore Technologies (Oxford, UK) measures picoamp changes in electrical current dependent on nucleotide sequences of the DNA strand migrating through nanopores in the system. The hardware is exceptionally small (9.5 x 3.2 x 1.6 cm), lightweight (120 grams), and powered only by a USB connection. For the ISS technology demonstration, the Biomolecule Sequencer will be powered by a Microsoft Surface Pro3. Ground-prepared samples containing lambda bacteriophage, Escherichia coli, and mouse genomic DNA, will be launched and stored frozen on the ISS until experiment initiation. Immediately prior to sequencing, a crew member will collect and thaw frozen DNA samples, connect the sequencer to the Surface Pro3, inject thawed samples into a MinION flow cell, and initiate sequencing. At the completion of the sequencing run, data will be downlinked for ground analysis. Identical, synchronous ground controls will be used for data comparisons to determine sequencer functionality, run-time sequence, current dynamics, and overall accuracy. We will present our latest results from the ISS flight experiment the first time DNA has ever been sequenced in space and discuss the many potential applications of the Biomolecule Sequencer for environmental monitoring, medical diagnostics, higher fidelity and more adaptable Space Biology Human Research Program investigations, and even life detection experiments for astrobiology missions

XSTREAM: A practical algorithm for identification and architecture modeling of tandem repeats in protein sequences

<p>Abstract</p> <p>Background</p> <p>Biological sequence repeats arranged in tandem patterns are widespread in DNA and proteins. While many software tools have been designed to detect DNA tandem repeats (TRs), useful algorithms for identifying protein TRs with varied levels of degeneracy are still needed.</p> <p>Results</p> <p>To address limitations of current repeat identification methods, and to provide an efficient and flexible algorithm for the detection and analysis of TRs in protein sequences, we designed and implemented a new computational method called XSTREAM. Running time tests confirm the practicality of XSTREAM for analyses of multi-genome datasets. Each of the key capabilities of XSTREAM (e.g., merging, nesting, long-period detection, and TR architecture modeling) are demonstrated using anecdotal examples, and the utility of XSTREAM for identifying TR proteins was validated using data from a recently published paper.</p> <p>Conclusion</p> <p>We show that XSTREAM is a practical and valuable tool for TR detection in protein and nucleotide sequences at the multi-genome scale, and an effective tool for modeling TR domains with diverse architectures and varied levels of degeneracy. Because of these useful features, XSTREAM has significant potential for the discovery of naturally-evolved modular proteins with applications for engineering novel biostructural and biomimetic materials, and identifying new vaccine and diagnostic targets.</p

Extra-curricular physical activity and socioeconomic status in Italian adolescents

BACKGROUND: The relationship between physical activity and health status has been thoroughly investigated in several studies, while the relation between physical activity and socio-economic status (SES) is less investigated. The aim of this study was to measure the extra-curricular physical activity of adolescents related to the socio-economic status (SES) of their families. METHODS: The survey was carried out by submitting an anonymous questionnaire to junior high school students in the following Regions: Lazio, Abruzzo, Molise, Campania, Puglia, during the school year 2002–2003. Extra-curriculum physical activity was evaluated considering whether or not present and hours of activity weekly conducted. 2411 students agreed to participate in the study. RESULTS: Participants were 1121 males (46.5%) and 1290 females (53.5%), aged between 11 and 17 years (median age: 12 years). 71.1% of the students reported to practice extra-curricular physical activity. Parents' educational levels and work activities play an important role in predicting students' physical activity, with the more remunerative activities and higher educational levels being more predictive. CONCLUSION: The results confirm the relationship between adolescents' physical activity and their families' SES. In particular, a positive relationship between participation in extra-curricular physical activity and their families high SES was found. These data will be useful for school administrators and for politicians in order to reduce the gap between adolescents from the least and most disadvantaged families

What Does the Geometry of the HβBLR Depend On?

We combine our dynamical modeling black-hole mass measurements from the Lick AGN Monitoring Project 2016 sample with measured cross-correlation time lags and line widths to recover individual scale factors, f, used in traditional reverberation-mapping analyses. We extend our sample by including prior results from Code for AGN Reverberation and Modeling of Emission Lines (CARAMEL) studies that have utilized our methods. Aiming to improve the precision of black-hole mass estimates, as well as uncover any regularities in the behavior of the broad-line region (BLR), we search for correlations between f and other AGN/BLR parameters. We find (i) evidence for a correlation between the virial coefficient log10(fmean,σ) and black-hole mass, (ii) marginal evidence for a similar correlation between log10( frms,σ) and black-hole mass, (iii) marginal evidence for an anticorrelation of BLR disk thickness with log10( fmean,FWHM) and log10( frms,FWHM), and (iv) marginal evidence for an anticorrelation of inclination angle with log10( fmean,FWHM), log10( frms,σ), and log10( fmean,σ). Last, we find marginal evidence for a correlation between line-profile shape, when using the root-mean-square spectrum, log10(FWHM/σ)rms, and the virial coefficient, log10( frms,σ), and investigate how BLR properties might be related to line-profile shape using CARAMEL models

Predicting Outcomes in Men With Metastatic Nonseminomatous Germ Cell Tumors (NSGCT): Results From the IGCCCG Update Consortium

Purpose: The classification of the International Germ Cell Cancer Collaborative Group (IGCCCG) plays a pivotal role in the management of metastatic germ cell tumors but relies on data of patients treated between 1975 and 1990. Materials and methods: Data on 9,728 men with metastatic nonseminomatous germ cell tumors treated with cisplatin- and etoposide-based first-line chemotherapy between 1990 and 2013 were collected from 30 institutions or collaborative groups in Europe, North America, and Australia. Clinical trial and registry data were included. Primary end points were progression-free survival (PFS) and overall survival (OS). The survival estimates were updated for the current era. Additionally, a novel prognostic model for PFS was developed in 3,543 patients with complete information on potentially relevant variables. The results were validated in an independent data set. Results: Compared with the original IGCCCG publication, 5-year PFS remained similar in patients with good prognosis with 89% (87%-91%) versus 90% (95% CI, 89 to 91), but the 5-year OS increased from 92% (90%-94%) to 96% (95%-96%). In patients with intermediate prognosis, PFS remained similar with 75% (71%-79%) versus 78% (76%-80%) and the OS increased from 80% (76%-84%) to 89% (88%-91%). In patients with poor prognosis, the PFS increased from 41% (95% CI, 35 to 47) to 54% (95% CI, 52 to 56) and the OS from 48% (95% CI, 42 to 54) to 67% (95% CI, 65 to 69). A more granular prognostic model was developed and independently validated. This model identified a new cutoff of lactate dehydrogenase at a 2.5 upper limit of normal and increasing age and presence of lung metastases as additional adverse prognostic factors. An online calculator is provided (https://www.eortc.org/IGCCCG-Update). Conclusion: The IGCCCG Update model improves individual prognostication in metastatic nonseminomatous germ cell tumors. Increasing age and lung metastases add granularity to the original IGCCCG classification as adverse prognostic factors