Revisiting Old Friends: Is CoDel Really Achieving What RED Cannot?

We use ns-2 simulations to compare RED's gentle mode to CoDel in terms of their ability to reduce the latency for various TCP variants. We use a common dumbbell topology with Pareto background traffic, and measure the packet delays and transmission time of a 10MB FTP transfer. In our scenarios, we find that CoDel reduces the latency by 87%, but RED still manages to reduce it by 75%. However, the use of CoDel results in a transmission time 42% longer than when using RED. In light of its maturity, we therefore argue that RED could be considered as a good candidate to tackle Bufferbloat

Editorial. Nomenclature - Avoiding Babylonian Speech Confusion in Present Day Immunology

The complexity of the immune system at the gene, protein, cell, and organism levels continues to provide a major challenge. Genomic landscaping, single-cell analysis and mass data acquisition including genome, transcriptome, metabolome, and proteome have now added new levels of complexity. With the rapid progress in these and other fields of immunology, it has become more important than ever to agree on uniform nomenclatures, i.e. to agree on how to name novel genes, proteins, cells, and biological reagents. Names given initially might, in retrospect, not always be logical. For example, tumor necrosis factor (TNF) was named on the basis of the observation of central necrosis in an experimental subcutaneous mouse tumor model (1). It was only after many unsuccessful studies in cancer, that eventually the role of TNF as a master cytokine in inflammation emerged. By that time, it was too late to rename the molecule because that would cause renewed confusion. Another cytokine has been successfully renamed. Interleukin-6 was initially known as B-cell Stimulatory Factor 2, Cytotoxic T lymphocyte Differentiation Factor, Hybridoma Growth Factor, Hepatocyte Stimulating Factor, and Interferon Beta-2. Obviously, such usage of different names for the same item can lead to confusion and may hinder progress in the field. These two examples demonstrate the need for a consensus nomenclature, which is timely applied

A new common functional coding variant at the DDC gene change renal enzyme activity and modify renal dopamine function.

The intra-renal dopamine (DA) system is highly expressed in the proximal tubule and contributes to Na+ and blood pressure homeostasis, as well as to the development of nephropathy. In the kidney, the enzyme DOPA Decarboxylase (DDC) originating from the circulation. We used a twin/family study design, followed by polymorphism association analysis at DDC locus to elucidate heritable influences on renal DA production. Dense single nucleotide polymorphism (SNP) genotyping across the DDC locus on chromosome 7p12 was analyzed by re-sequencing guided by trait-associated genetic markers to discover the responsible genetic variation. We also characterized kinetics of the expressed DDC mutant enzyme. Systematic polymorphism screening across the 15-Exon DDC locus revealed a single coding variant in Exon-14 that was associated with DA excretion and multiple other renal traits indicating pleiotropy. When expressed and characterized in eukaryotic cells, the 462Gln variant displayed lower Vmax (maximal rate of product formation by an enzyme) (21.3 versus 44.9 nmol/min/mg) and lower Km (substrate concentration at which half-maximal product formation is achieved by an enzyme.)(36.2 versus 46.8 μM) than the wild-type (Arg462) allele. The highly heritable DA excretion trait is substantially influenced by a previously uncharacterized common coding variant (Arg462Gln) at the DDC gene that affects multiple renal tubular and glomerular traits, and predicts accelerated functional decline in chronic kidney disease

The DEEP Groth Strip Survey IX: Evolution of the Fundamental Plane of Field Galaxies

Fundamental Plane studies provide an excellent means of understanding the evolutionary history of early-type galaxies. Using the Low Resolution Imaging Spectrograph on the Keck telescope, we obtained internal stellar kinematic information for 36 field galaxies in the Groth Strip--21 early-type and 15 disk galaxies. Their redshifts range from 0.3--1.0, with a median redshift 0.8. The slope of the relation shows no difference compared with the local slope. However, there is significant evolution in the zero-point offset; an offset due to evolution in magnitude requires a 2.4 magnitude luminosity brightening at z=1. We see little differences of the offset with bulge fraction, which is a good surrogate for galaxy type. Correcting for the luminosity evolution reduces the orthogonal scatter in the Fundamental Plane to 8%, consistent with the local scatter. This scatter is measured for our sample, and does not include results from other studies which may have different selection effects. The difference in the degree of evolution between our field sample and published cluster galaxies suggests a more recent formation epoch--around z=1.5 for field galaxies compared to z>2.0 for cluster galaxies. The magnitude difference implies that the field early-type galaxies are about 2 Gyr younger than the cluster ellipticals using standard single-burst models. However, the same models imply a significant change in the rest-frame U-B color from then to present, which is not seen in our sample. Continuous low-level star formation, however, would serve to explain the constant colors over this large magnitude change. A consistent model has 7% of the stellar mass created after the initial burst, using an exponentially decaying star formation rate with an e-folding time of 5 Gyr.Comment: 25 pages, accepted for publication in the Astrophysical Journal, high resolution version at http://hoku.as.utexas.edu/~gebhardt/FPpaper.p

Widespread seasonal gene expression reveals annual differences in human immunity and physiology.

Seasonal variations are rarely considered a contributing component to human tissue function or health, although many diseases and physiological process display annual periodicities. Here we find more than 4,000 protein-coding mRNAs in white blood cells and adipose tissue to have seasonal expression profiles, with inverted patterns observed between Europe and Oceania. We also find the cellular composition of blood to vary by season, and these changes, which differ between the United Kingdom and The Gambia, could explain the gene expression periodicity. With regards to tissue function, the immune system has a profound pro-inflammatory transcriptomic profile during European winter, with increased levels of soluble IL-6 receptor and C-reactive protein, risk biomarkers for cardiovascular, psychiatric and autoimmune diseases that have peak incidences in winter. Circannual rhythms thus require further exploration as contributors to various aspects of human physiology and disease.The Gambian study providing data for analysis was supported by core funding MC-A760-5QX00 to the International Nutrition Group by the UK Medical Research Council (MRC) and the UK Department for the International Development (DFID) under the MRC/DFID Concordat agreement. This work was supported by the JDRF UK Centre for Diabetes-Genes, Autoimmunity and Prevention (D-GAP; 4-2007-1003), the JDRF (9-2011-253), the Wellcome Trust (WT061858/091157), the National Institute for Health Research Cambridge Biomedical Research Centre (CBRC) and the Medical Research Council (MRC) Cusrow Wadia Fund. The research leading to these results has received funding from the European Union’s 7th Framework Programme (FP7/2007–2013) under grant agreement no.241447 (NAIMIT). The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (WT100140). X.C.D. was a University of Cambridge/Wellcome Trust Infection and Immunity PhD student. R.C.F. is funded by a JDRF post-doctoral fellowship (3-2011-374). C.W. and H.G are funded by the Wellcome Trust (WT089989). The BABYDIET study was supported by grants from the Deutsche Forschungsgemeinschaft (DFG ZI-310/14-1 to-4), the JDRF (JDRF 17-2012-16 and 1-2006-665) and the German Center for Diabetes Research (DZD e.V.). E.B. is supported by the DFG Research Center and Cluster of Excellence—Center for Regenerative Therapies Dresden (FZ 111).This is the final published version. It first appeared at http://www.nature.com/ncomms/2015/150512/ncomms8000/full/ncomms8000.html

Two Small Temperate Planets Transiting Nearby M Dwarfs in K2 Campaigns 0 and 1

The prime Kepler mission revealed that small planets (<4 R_⊕) are common, especially around low-mass M dwarfs. K2, the repurposed Kepler mission, continues this exploration of small planets around small stars. Here we combine K2 photometry with spectroscopy, adaptive optics imaging, and archival survey images to analyze two small planets orbiting the nearby field-age M dwarfs, K2-26 (EPIC 202083828) and K2-9. K2-26 is an M 1.0 ± 0.5 dwarf at 93 ± 7 pc from K2 Campaign 0. We validate its planet with a day period of 14.5665 and estimate a radius of 2.67_(-0.42)^(+0.46)R_⊕. K2-9 is an M2.5 ± 0.5 dwarf at 110 ± 12 pc from K2 Campaign 1. K2-9b was first identified by Montet et al.; here we present spectra and adaptive optics imaging of the host star and independently validate and characterize the planet. Our analyses indicate K2-9b is a 2.25_(-0.96)^(+0.53)R_⊕ planet with a 18.4498 day period. K2-26b exhibits a transit duration that is too long to be consistent with a circular orbit given its measured stellar radius. Thus, the long transits are likely due to the photoeccentric effect and our transit fits hint at an eccentric orbit. Both planets receive low incident flux from their host stars and have estimated equilibrium temperatures <500 K. K2-9b may receive approximately Earth-like insolation. However, its host star exhibits strong GALEX UV emission which could affect any atmosphere it harbors. K2-26b and K2-9b are representatives of a poorly studied class of small planets with cool temperatures that have radii intermediate to Earth and Neptune. Future study of these systems can provide key insight into trends in bulk composition and atmospheric properties at the transition from silicate dominated to volatile rich bodies

Biological, clinical and population relevance of 95 loci for blood lipids.

Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in &gt;100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P &lt; 5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD

Consensus Guidelines for Advancing Coral Holobiont Genome and Specimen Voucher Deposition

Coral research is being ushered into the genomic era. To fully capitalize on the potential discoveries from this genomic revolution, the rapidly increasing number of high-quality genomes requires effective pairing with rigorous taxonomic characterizations of specimens and the contextualization of their ecological relevance. However, to date there is no formal framework that genomicists, taxonomists, and coral scientists can collectively use to systematically acquire and link these data. Spurred by the recently announced “Coral symbiosis sensitivity to environmental change hub” under the “Aquatic Symbiosis Genomics Project” - a collaboration between the Wellcome Sanger Institute and the Gordon and Betty Moore Foundation to generate gold-standard genome sequences for coral animal hosts and their associated Symbiodiniaceae microalgae (among the sequencing of many other symbiotic aquatic species) - we outline consensus guidelines to reconcile different types of data. The metaorganism nature of the coral holobiont provides a particular challenge in this context and is a key factor to consider for developing a framework to consolidate genomic, taxonomic, and ecological (meta)data. Ideally, genomic data should be accompanied by taxonomic references, i.e., skeletal vouchers as formal morphological references for corals and strain specimens in the case of microalgal and bacterial symbionts (cultured isolates). However, exhaustive taxonomic characterization of all coral holobiont member species is currently not feasible simply because we do not have a comprehensive understanding of all the organisms that constitute the coral holobiont. Nevertheless, guidelines on minimal, recommended, and ideal-case descriptions for the major coral holobiont constituents (coral animal, Symbiodiniaceae microalgae, and prokaryotes) will undoubtedly help in future referencing and will facilitate comparative studies. We hope that the guidelines outlined here, which we will adhere to as part of the Aquatic Symbiosis Genomics Project sub-hub focused on coral symbioses, will be useful to a broader community and their implementation will facilitate cross- and meta-data comparisons and analyses.CV acknowledges funding from the German Research Foundation (DFG), grants 433042944 and 458901010. Open Access publication fees are covered by an institutional agreement of the University of Konstanz

Hundreds of variants clustered in genomic loci and biological pathways affect human height

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.