LONGO: An R package for interactive gene length dependent analysis for neuronal identity

Motivation: Reprogramming somatic cells into neurons holds great promise to model neuronal development and disease. The efficiency and success rate of neuronal reprogramming, however, may vary between different conversion platforms and cell types, thereby necessitating an unbiased, systematic approach to estimate neuronal identity of converted cells. Recent studies have demonstrated that long genes (\u3e100 kb from transcription start to end) are highly enriched in neurons, which provides an opportunity to identify neurons based on the expression of these long genes. Results: We have developed a versatile R package, LONGO, to analyze gene expression based on gene length. We propose a systematic analysis of long gene expression (LGE) with a metric termed the long gene quotient (LQ) that quantifies LGE in RNA-seq or microarray data to validate neuronal identity at the single-cell and population levels. This unique feature of neurons provides an opportunity to utilize measurements of LGE in transcriptome data to quickly and easily distinguish neurons from non-neuronal cells. By combining this conceptual advancement and statistical tool in a user-friendly and interactive software package, we intend to encourage and simplify further investigation into LGE, particularly as it applies to validating and improving neuronal differentiation and reprogramming methodologies. Availability and implementation: LONGO is freely available for download at https://github.com/biohpc/longo. Supplementary information: Supplementary data are available at Bioinformatics online

A New Ocean State After Nuclear War

Nuclear war would produce dire global consequences for humans and our environment. We simulated climate impacts of US-Russia and India-Pakistan nuclear wars in an Earth System Model, here, we report on the ocean impacts. Like volcanic eruptions and large forest fires, firestorms from nuclear war would transport light-blocking aerosols to the stratosphere, resulting in global cooling. The ocean responds over two timescales: a rapid cooling event and a long recovery, indicating a hysteresis response of the ocean to global cooling. Surface cooling drives sea ice expansion, enhanced meridional overturning, and intensified ocean vertical mixing that is expanded, deeper, and longer lasting. Phytoplankton production and community structure are highly modified by perturbations to light, temperature, and nutrients, resulting in initial decimation of production, especially at high latitudes. A new physical and biogeochemical ocean state results, characterized by shallower pycnoclines, thermoclines, and nutriclines, ventilated deep water masses, and thicker Arctic sea ice. Persistent changes in nutrient limitation drive a shift in phytoplankton community structure, resulting in increased diatom populations, which in turn increase iron scavenging and iron limitation, especially at high latitudes. In the largest US-Russia scenario (150 Tg), ocean recovery is likely on the order of decades at the surface and hundreds of years at depth, while changes to Arctic sea-ice will likely last thousands of years, effectively a “Nuclear Little Ice Age.” Marine ecosystems would be highly disrupted by both the initial perturbation and in the new ocean state, resulting in long-term, global impacts to ecosystem services such as fisheries.publishedVersio

Silymarin in non-cirrhotics with non-alcoholic steatohepatitis: A randomized, double-blind, placebo controlled trial

The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease and may be a treatment for NASH due to its antioxidant properties. We aimed to assess the safety and efficacy of higher than customary doses of silymarin in non-cirrhotic patients with NASH. This exploratory randomized double-blind placebo controlled multicenter Phase II trial tested a proprietary standardized silymarin preparation (Legalon®, Rottapharm|Madaus, Mylan) and was conducted at 5 medical centers in the United States. Eligible adult patients had liver biopsy within 12 months showing NASH without cirrhosis with NAFLD Activity Score (NAS) ≥4 per site pathologist\u27s assessment. Participants were randomized to Legalon® 420 mg, 700 mg, or placebo t.i.d. for 48 weeks. The primary endpoint was histological improvement ≥2 points in NAS. Of 116 patients screened, 78 were randomized. There were no significant differences in adverse events among the treatment groups. After 48-50 weeks, 4/27 (15%) in the 700 mg dose, 5/26 (19%) participants randomized to 420 mg, and 3/25 (12%) of placebo recipients reached the primary endpoint (p = 0.79) among all randomized participants, indicating no benefit from silymarin in the intention to treat analysis Review by a central pathologist demonstrated that a substantial number of participants (49, 63%) did not meet histological entry criteria and that fibrosis stage improved most in the placebo treated group, although not significantly different from other groups. Silymarin (Legalon®) at the higher than customary doses tested in this study is safe and well tolerated. The effect of silymarin in patients with NASH remains inconclusive due to the substantial number of patients who entered the study but did not meet entry histological criteria, the lack of a statistically significant improvement in NAS of silymarin treated patients, and the unanticipated effect of placebo on fibrosis indicate the need for additional clinical trials. Trial Registration: clinicaltrials.gov, Identifier: NCT00680407

A theorem proving framework for the formal verification of Web Services Composition

We present a rigorous framework for the composition of Web Services within a higher order logic theorem prover. Our approach is based on the proofs-as-processes paradigm that enables inference rules of Classical Linear Logic (CLL) to be translated into pi-calculus processes. In this setting, composition is achieved by representing available web services as CLL sentences, proving the requested composite service as a conjecture, and then extracting the constructed pi-calculus term from the proof. Our framework, implemented in HOL Light, not only uses an expressive logic that allows us to incorporate multiple Web Services properties in the composition process, but also provides guarantees of soundness and correctness for the composition.Comment: In Proceedings WWV 2011, arXiv:1108.208

A Mixed-Method Evaluation of a Rural Elementary School Implementing the Coordinated Approach to Child Health (CATCH) Program

Despite children living in rural US areas having 26% greater odds of being affected by obesity compared to those living in urban areas, the implementation of evidence-based programs in rural schools is rare. We collected quantitative data (weight and height) from 272 racially and ethnically diverse students at baseline, and qualitative data from students (4 focus groups), parents, and school staff (16 semi-structured interviews and 29 surveys) to evaluate program outcomes and perceptions. At the 2-year follow-up, paired data from 157 students, represented by racial/ethnic groups of 59% non-Hispanic White, 31% non-Hispanic Black, and 10% Hispanic, showed an overall mean change (SD) in BMI z-score of −0.04 (0.59), a decrease of −0.08 (0.69) in boys, and a significant −0.18 (0.33) decrease among Hispanic students. Boys had a mean decrease in obesity prevalence of 3 percentage points (from 17% to 14%), and Hispanic students had the largest mean decrease in BMI percentile. Qualitative data showed positive perceptions of the CATCH program and its implementation. This community-engaged research, with collaboration from an academic institution, a health department, a local wellness coalition, and a rural elementary school, demonstrated successful CATCH program implementation and showed promising outcomes in mean BMI changes

Measurement of the cosmic ray spectrum above 4×10184{\times}10^{18} eV using inclined events detected with the Pierre Auger Observatory

A measurement of the cosmic-ray spectrum for energies exceeding $4{\times}10^{18}$ eV is presented, which is based on the analysis of showers with zenith angles greater than $60^{\circ}$ detected with the Pierre Auger Observatory between 1 January 2004 and 31 December 2013. The measured spectrum confirms a flux suppression at the highest energies. Above $5.3{\times}10^{18}$ eV, the "ankle", the flux can be described by a power law $E^{-\gamma}$ with index $\gamma=2.70 \pm 0.02 \,\text{(stat)} \pm 0.1\,\text{(sys)}$ followed by a smooth suppression region. For the energy ($E_\text{s}$) at which the spectral flux has fallen to one-half of its extrapolated value in the absence of suppression, we find $E_\text{s}=(5.12\pm0.25\,\text{(stat)}^{+1.0}_{-1.2}\,\text{(sys)}){\times}10^{19}$ eV.Comment: Replaced with published version. Added journal reference and DO