Cloud Computing for Next-Generation Sequencing Data Analysis

High-throughput next-generation sequencing (NGS) technologies have evolved rapidly and are reshaping the scope of genomics research. The substantial decrease in the cost of NGS techniques in the past decade has led to its rapid adoption in biological research and drug development. Genomics studies of large populations are producing a huge amount of data, giving rise to computational issues around the storage, transfer, and analysis of the data. Fortunately, cloud computing has recently emerged as a viable option to quickly and easily acquire the computational resources for large-scale NGS data analyses. Some cloud-based applications and resources have been developed specifically to address the computational challenges of working with very large volumes of data generated by NGS technology. In this chapter, we will review some cloud-based systems and solutions for NGS data analysis, discuss the practical hurdles and limitations in cloud computing, including data transfer and security, and share the lessons we learned from the implementation of Rainbow, a cloud-based tool for large-scale genome sequencing data analysis

Cardiorespiratory fitness levels and body mass index of pre-adolescent children and older adults during the COVID-19 pandemic

IntroductionThe social and behavioral effects of the COVID-19 pandemic have impacted the health and physiology of most people, including those never diagnosed with COVID-19. While the impact of the pandemic has been felt across the lifespan, its effects on cardiorespiratory fitness (commonly considered a reflection of total body health) of older adults and children may be particularly profound due to social distancing and stay-at-home advisories, as well as the closure of sport facilities and non-essential businesses. The objective of this investigation was to leverage baseline data from two ongoing clinical trials to determine if cardiorespiratory fitness and body mass index were different during COVID-19 relative to before COVID-19 in older adults and children.MethodsHealthy older individuals (N = 593; 65–80 years) and 200 typically developing children (8–10 years) completed a graded maximal exercise test and had their height and weight measured.ResultsResults revealed that older adults and children tested during COVID-19 had significantly lower cardiorespiratory fitness levels than those tested before COVID-19 shutdowns (older adults: 30% lower; children: 53% lower; p's ≤ 0.001). In addition, older adults and children tested during COVID-19 had significantly higher BMI (older adults: 31.34 ± 0.57 kg/m2, p = 0.004; children: 19.27 ± 0.44 kg/m2, p = 0.05) than those tested before COVID-19 shutdowns (older adults: 29.51 ± 0.26 kg/m2, children: 18.13 ± 0.35 kg/m2). However, these differences in BMI did not remain significant when controlling for cardiorespiratory fitness.DiscussionResults from this investigation indicate that the COVID-19 pandemic, and behavior changes taken to reduce potential exposure, may have led to lower cardiorespiratory fitness levels in older adults and children, as well as higher body mass index. These findings provide relevant public health information as lower cardiorespiratory fitness levels and higher body mass indexes recorded during the pandemic could have far-reaching and protracted health consequences. Public health guidance is needed to encourage physical activity to maintain cardiorespiratory fitness and healthy body composition.Clinical trial registrationOlder adults: https://clinicaltrials.gov/ct2/show/NCT02875301, identifier: NCT02875301; Children: https://clinicaltrials.gov/ct2/show/NCT03592238, identifier: NCT03592238

Higher docosahexaenoic acid levels lower the protective impact of eicosapentaenoic acid on long-term major cardiovascular events

IntroductionLong-chain omega-3 polyunsaturated fatty acids (OM3 PUFA) are commonly used for cardiovascular disease prevention. High-dose eicosapentaenoic acid (EPA) is reported to reduce major adverse cardiovascular events (MACE); however, a combined EPA and docosahexaenoic acid (DHA) supplementation has not been proven to do so. This study aimed to evaluate the potential interaction between EPA and DHA levels on long-term MACE.MethodsWe studied a cohort of 987 randomly selected subjects enrolled in the INSPIRE biobank registry who underwent coronary angiography. We used rapid throughput liquid chromatography-mass spectrometry to quantify the EPA and DHA plasma levels and examined their impact unadjusted, adjusted for one another, and fully adjusted for comorbidities, EPA + DHA, and the EPA/DHA ratio on long-term (10-year) MACE (all-cause death, myocardial infarction, stroke, heart failure hospitalization).ResultsThe average subject age was 61.5 ± 12.2 years, 57% were male, 41% were obese, 42% had severe coronary artery disease (CAD), and 311 (31.5%) had a MACE. The 10-year MACE unadjusted hazard ratio (HR) for the highest (fourth) vs. lowest (first) quartile (Q) of EPA was HR = 0.48 (95% CI: 0.35, 0.67). The adjustment for DHA changed the HR to 0.30 (CI: 0.19, 0.49), and an additional adjustment for baseline differences changed the HR to 0.36 (CI: 0.22, 0.58). Conversely, unadjusted DHA did not significantly predict MACE, but adjustment for EPA resulted in a 1.81-fold higher risk of MACE (CI: 1.14, 2.90) for Q4 vs. Q1. However, after the adjustment for baseline differences, the risk of MACE was not significant for DHA (HR = 1.37; CI: 0.85, 2.20). An EPA/DHA ratio ≥1 resulted in a lower rate of 10-year MACE outcomes (27% vs. 37%, adjusted p-value = 0.013).ConclusionsHigher levels of EPA, but not DHA, are associated with a lower risk of MACE. When combined with EPA, higher DHA blunts the benefit of EPA and is associated with a higher risk of MACE in the presence of low EPA. These findings can help explain the discrepant results of EPA-only and EPA/DHA mixed clinical supplementation trials

Solid Dielectric Transmission Lines for Pulsed Power

This paper documents recent work developing solid dielectric transmission lines for sub-microsecond, 100 kV class compact pulsed power systems. Polymer-ceramic nanocomposite materials have demonstrated sub-microsecond discharge capability in parallel plate capacitors and transmission lines [1, 2]. With a dielectric constant of approximately 50, the propagation velocity is 2.5 cm/ns, necessitating lines of several meters length to achieve \u3e 100 ns pulse lengths. By folding the line in a fashion analogous to ceramic multilayer capacitors, the physical length of the line can be significantly shorter than the electrical length. We present the results of an experimental effort to develop a folded transmission line using a polymer-ceramic nanocomposite dielectric. The pulse length was somewhat shorter than expected based on a simple calculation using the geometry and the dielectric constant. Fully 3-D electromagnetic calculations were used to examine the role of the edges in curtailing the pulse length. Dielectric breakdown in this device occurred below the electric field threshold demonstrated in the prior work [1]. Improvements in the large scale fabrication of TiO2 beginning with nanoscale grains have opened the possibility for producing single layer high voltage devices. Given a dielectric constant approaching 140, transmission lines using nano-TiO2 can be considerably shorter than with other materials. Relatively thick, flat sheets of TiO2 have been fabricated for testing up to 50 kV. Several transmission lines, employing a serpentine electrode geometry, have been manufactured and tested. Testing up to several 10\u27s of kV has confirmed the operation of the lines according to the design. As expected, the triple point between the TiO2, electrode, and insulating medium has proven difficult to manage for high voltage operation. Several techniques to mitigate the effects of the triple point, including resistive grading at the edges of the electrodes, are discussed. Fully 3-D electromagnetic modeling is used to examine the effects of electrode geometry and composition on the performance of the lines

Dung-inhabiting fungi: a potential reservoir of novel secondary metabolites for the control of plant pathogens

Coprophilous fungi are a large group of saprotrophic fungi, mostly found in herbivore dung. The number of these fungi are investigated is continuously increasing and new species and genera continue to be described. Dung-inhabiting fungi play an important ecological role in decomposing and recycling nutrients from animal dung. They produce a large array of bioactive secondary metabolites and have a potent enzymatic arsenal able to utilize even complex molecules. Bioactive secondary metabolites are actively involved in the interaction with and defence against other organisms whose growth can be inhibited, resulting in an enhanced ecological fitness of producer strains. Currently these antibiotics and bioactive secondary metabolites are of interest especially in medicine, while very little information is available concerning their potential use in agriculture. This review introduces the ecology of dung-inhabiting fungi with particular emphasis on the production of antibiotic compounds as a mean to compete with other microorganisms. Due to the fast pace of technological progress, new approaches are proposed in order to predict the biosynthesis of bioactive metabolites. Coprophilous fungi should be considered as elite candidate organisms for the discovery of novel antifungal compounds, above all in view of their exploitation for crop protection