Predicting Convection Configurations in Coupled Fluid-Porous Systems

A ubiquitous arrangement in nature is a free-flowing fluid coupled to a porous medium, for example a river or lake lying above a porous bed. Depending on the environmental conditions, thermal convection can occur and may be confined to the clear fluid region, forming shallow convection cells, or it can penetrate into the porous medium, forming deep cells. Here, we combine three complementary approaches - linear stability analysis, fully nonlinear numerical simulations and a coarse-grained model - to determine the circumstances that lead to each configuration. the coarse-grained model yields an explicit formula for the transition between deep and shallow convection in the physically relevant limit of small Darcy number. Near the onset of convection, all three of the approaches agree, validating the predictive capability of the explicit formula. the numerical simulations extend these results into the strongly nonlinear regime, revealing novel hybrid configurations in which the flow exhibits a dynamic shift from shallow to deep convection. This hybrid shallow-to-deep convection begins with small, random initial data, progresses through a metastable shallow state and arrives at the preferred steady state of deep convection. We construct a phase diagram that incorporates information from all three approaches and depicts the regions in parameter space that give rise to each convective state

Fibroblast and Lymphoblast Gene Expression Profiles in Schizophrenia: Are Non-Neural Cells Informative?

Lymphoblastoid cell lines (LCLs) and fibroblasts provide conveniently derived non-neuronal samples in which to investigate the aetiology of schizophrenia (SZ) using gene expression profiling. This assumes that heritable mechanisms associated with risk of SZ have systemic effects and result in changes to gene expression in all tissues. The broad aim of this and other similar studies is that comparison of the transcriptomes of non-neuronal tissues from SZ patients and healthy controls may identify gene/pathway dysregulation underpinning the neurobiological defects associated with SZ. Using microarrays consisting of 18,664 probes we compared gene expression profiles of LCLs from SZ cases and healthy controls. To identify robust associations with SZ that were not patient or tissue specific, we also examined fibroblasts from an independent series of SZ cases and controls using the same microarrays. In both tissue types ANOVA analysis returned approximately the number of differentially expressed genes expected by chance. No genes were significantly differentially expressed in either tissue when corrected for multiple testing. Even using relaxed parameters (p≤0.05, without multiple testing correction) there were still no differentially expressed genes that also displayed ≥2-fold change between the groups of SZ cases and controls common to both LCLs and fibroblasts. We conclude that despite encouraging data from previous microarray studies assessing non-neural tissues, the lack of a convergent set of differentially expressed genes associated with SZ using fibroblasts and LCLs indicates the utility of non-neuronal tissues for detection of gene expression differences and/or pathways associated with SZ remains to be demonstrated

New M, L, and T Dwarf Companions to Nearby Stars from the Wide-field Infrared Survey Explorer

We present 11 candidate late-type companions to nearby stars identified with data from the Wide-field Infrared Survey Explorer (WISE) and the Two Micron All Sky Survey (2MASS). Eight of the candidates are likely to be companions based on their common proper motions with the primaries. The remaining three objects are rejected as companions, one of which is a free-floating T7 dwarf. Spectral types are available for five of the companions, which consist of M2V, M8.5V, L5, T8, and T8. Based on their photometry, the unclassified companions are probably two mid-M dwarfs and one late-M/early-L dwarf. One of the T8 companions, WISE J142320.84+011638.0, has already been reported by Pinfield and coworkers. The other T8 companion, ULAS J095047.28+011734.3, was discovered by Burningham and coworkers through the United Kingdom Infrared Telescope Infrared Deep Sky Survey, but its companionship has not been previously recognized in the literature. The L5 companion, 2MASS J17430860+8526594, is a new member of a class of L dwarfs that exhibit unusually blue near-IR colors. Among the possible mechanisms that have been previously proposed for the peculiar colors of these L dwarfs, low metallicity does not appear to be a viable explanation for 2MASS J17430860+8526594 since our spectrum of the primary suggests that its metallicity is not significantly subsolar

Involvement of Hypoxia-Inducible Factor-1 in the Inflammatory Responses of Human LAD2 Mast Cells and Basophils

We recently showed that hypoxia-inducible factor 1 (HIF-1) plays a crucial role in the pro-allergic functions of human basophils by transcriptional control of energy metabolism via glycolysis as well as directly triggering expression of the angiogenic cytokine vascular endothelium growth factor (VEGF). Here, we investigated HIF-1 involvement in controlling the synthesis of angiogenic and inflammatory cytokines from various human effector cells stimulated by IgE-dependent or innate immune triggers. Purified primary human basophils, LAD2 human mast cells and THP-1 human myeloid cells were used for investigations of FcεRI and Toll-like receptor (TLR) ligand-induced responses. In contrast to basophils, LAD2 mast cells expressed background levels of HIF-1α, which was largely independent of the effects of stem cell factor (SCF). Both mast cells and basophils expressed TLR2 and 4, albeit weakly compared to THP-1 cells. Cytokine production in mast cells following TLR ligand stimulation was markedly reduced by HIF-1α knockdown in LAD2 mast cells. In contrast, although HIF-1 is involved in IgE-mediated IL-4 secretion from basophils, it is not clearly induced by peptidoglycan (PGN). HIF-1α accumulation is critical for sustaining human allergic effector cell survival and function. This transcription complex facilitates generation of both pro-angiogenic and inflammatory cytokines in mast cells but has a differential role in basophil stimulation comparing IgE-dependent triggering with innate immune stimuli

What we have learned from the framework for ocean observing: evolution of the global ocean observing system

The Global Ocean Observing System (GOOS) and its partners have worked together over the past decade to break down barriers between open-ocean and coastal observing, between scientific disciplines, and between operational and research institutions. Here we discuss some GOOS successes and challenges from the past decade, and present ideas for moving forward, including highlights of the GOOS 2030 Strategy, published in 2019. The OceanObs’09 meeting in Venice in 2009 resulted in a remarkable consensus on the need for a common set of guidelines for the global ocean observing community. Work following the meeting led to development of the Framework for Ocean Observing (FOO) published in 2012 and adopted by GOOS as a foundational document that same year. The FOO provides guidelines for the setting of requirements, assessing technology readiness, and assessing the usefulness of data and products for users. Here we evaluate successes and challenges in FOO implementation and consider ways to ensure broader use of the FOO principles. The proliferation of ocean observing activities around the world is extremely diverse and not managed, or even overseen by, any one entity. The lack of coherent governance has resulted in duplication and varying degrees of clarity, responsibility, coordination and data sharing. GOOS has had considerable success over the past decade in encouraging voluntary collaboration across much of this broad community, including increased use of the FOO guidelines and partly effective governance, but much remains to be done. Here we outline and discuss several approaches for GOOS to deliver more effective governance to achieve our collective vision of fully meeting society’s needs. What would a more effective and well-structured governance arrangement look like? Can the existing system be modified? Do we need to rebuild it from scratch? We consider the case for evolution versus revolution. Community-wide consideration of these governance issues will be timely and important before, during and following the OceanObs’19 meeting in September 2019

A Cross-Study Transcriptional Analysis of Parkinson's Disease

The study of Parkinson's disease (PD), like other complex neurodegenerative disorders, is limited by access to brain tissue from patients with a confirmed diagnosis. Alternatively the study of peripheral tissues may offer some insight into the molecular basis of disease susceptibility and progression, but this approach still relies on brain tissue to benchmark relevant molecular changes against. Several studies have reported whole-genome expression profiling in post-mortem brain but reported concordance between these analyses is lacking. Here we apply a standardised pathway analysis to seven independent case-control studies, and demonstrate increased concordance between data sets. Moreover data convergence increased when the analysis was limited to the five substantia nigra (SN) data sets; this highlighted the down regulation of dopamine receptor signaling and insulin-like growth factor 1 (IGF1) signaling pathways. We also show that case-control comparisons of affected post mortem brain tissue are more likely to reflect terminal cytoarchitectural differences rather than primary pathogenic mechanisms. The implementation of a correction factor for dopaminergic neuronal loss predictably resulted in the loss of significance of the dopamine signaling pathway while axon guidance pathways increased in significance. Interestingly the IGF1 signaling pathway was also over-represented when data from non-SN areas, unaffected or only terminally affected in PD, were considered. Our findings suggest that there is greater concordance in PD whole-genome expression profiling when standardised pathway membership rather than ranked gene list is used for comparison

Software for the frontiers of quantum chemistry:An overview of developments in the Q-Chem 5 package

This article summarizes technical advances contained in the fifth major release of the Q-Chem quantum chemistry program package, covering developments since 2015. A comprehensive library of exchange–correlation functionals, along with a suite of correlated many-body methods, continues to be a hallmark of the Q-Chem software. The many-body methods include novel variants of both coupled-cluster and configuration-interaction approaches along with methods based on the algebraic diagrammatic construction and variational reduced density-matrix methods. Methods highlighted in Q-Chem 5 include a suite of tools for modeling core-level spectroscopy, methods for describing metastable resonances, methods for computing vibronic spectra, the nuclear–electronic orbital method, and several different energy decomposition analysis techniques. High-performance capabilities including multithreaded parallelism and support for calculations on graphics processing units are described. Q-Chem boasts a community of well over 100 active academic developers, and the continuing evolution of the software is supported by an “open teamware” model and an increasingly modular design

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Evolving and sustaining ocean best practices and standards for the next decade

The oceans play a key role in global issues such as climate change, food security, and human health. Given their vast dimensions and internal complexity, efficient monitoring and predicting of the planet’s ocean must be a collaborative effort of both regional and global scale. A first and foremost requirement for such collaborative ocean observing is the need to follow well-defined and reproducible methods across activities: from strategies for structuring observing systems, sensor deployment and usage, and the generation of data and information products, to ethical and governance aspects when executing ocean observing. To meet the urgent, planet-wide challenges we face, methods across all aspects of ocean observing should be broadly adopted by the ocean community and, where appropriate, should evolve into “Ocean Best Practices.” While many groups have created best practices, they are scattered across the Web or buried in local repositories and many have yet to be digitized. To reduce this fragmentation, we introduce a new open access, permanent, digital repository of best practices documentation (oceanbestpractices.org) that is part of the Ocean Best Practices System (OBPS). The new OBPS provides an opportunity space for the centralized and coordinated improvement of ocean observing methods. The OBPS repository employs user-friendly software to significantly improve discovery and access to methods. The software includes advanced semantic technologies for search capabilities to enhance repository operations. In addition to the repository, the OBPS also includes a peer reviewed journal research topic, a forum for community discussion and a training activity for use of best practices. Together, these components serve to realize a core objective of the OBPS, which is to enable the ocean community to create superior methods for every activity in ocean observing from research to operations to applications that are agreed upon and broadly adopted across communities. Using selected ocean observing examples, we show how the OBPS supports this objective. This paper lays out a future vision of ocean best practices and how OBPS will contribute to improving ocean observing in the decade to come