Seasonal and Spatial Variation in the Location and Reactivity of a Nitrate‐Contaminated Groundwater Discharge Zone in a Lakebed

Groundwater discharge delivering anthropogenic N from surrounding watersheds can impact lake nutrient budgets. However, upgradient groundwater processes and changing dynamics in N biogeochemistry at the groundwater‐lake interface are complex. In this study, seasonal water‐level variations in a groundwater flow‐through lake altered discharge patterns of a wastewater‐derived groundwater contaminant plume, thereby affecting biogeochemical processes controlling N transport. Pore water collected 15 cm under the lakebed along transects perpendicular to shore varied from oxic to anoxic with increasing nitrate concentrations (10–75 μM) and corresponding gradients in nitrite and nitrous oxide. Pore water depth profiles of nitrate concentrations and stable isotopic compositions largely reflected upgradient groundwater N sources and N cycle processes, with minor additional nitrate reduction in the near‐surface lakebed sediments. Potential denitrification rates determined in laboratory microcosms were 10–100 times higher in near‐surface sediments (0–5 cm) than in deeper sediments (5–30 cm) and were correlated with sediment carbon content and abundance of denitrification genes (nirS, nosZI, and nosZII). Potential anammox‐driven N2 production was detectable in deeper anoxic sediments. Injection of bromide and nitrite in the lake sediments showed that the highest net nitrite consumption rates were within the top 10 cm. However, short transit times owing to rapid upward pore water velocities (4–5 cm hr−1) limited removal of the contaminant nitrate transiting through the sediments. Results demonstrate that local hydrologic and biogeochemical processes at the point of discharge affect the distribution and discharge rate of N through lakebed sediments, but processes in the upgradient groundwater can be more important for affecting N speciation and concentration

Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal

Mounting evidence suggests that there is frequently considerable variation in the risk of the outcome of interest in clinical trial populations. These differences in risk will often cause clinically important heterogeneity in treatment effects (HTE) across the trial population, such that the balance between treatment risks and benefits may differ substantially between large identifiable patient subgroups; the "average" benefit observed in the summary result may even be non-representative of the treatment effect for a typical patient in the trial. Conventional subgroup analyses, which examine whether specific patient characteristics modify the effects of treatment, are usually unable to detect even large variations in treatment benefit (and harm) across risk groups because they do not account for the fact that patients have multiple characteristics simultaneously that affect the likelihood of treatment benefit. Based upon recent evidence on optimal statistical approaches to assessing HTE, we propose a framework that prioritizes the analysis and reporting of multivariate risk-based HTE and suggests that other subgroup analyses should be explicitly labeled either as primary subgroup analyses (well-motivated by prior evidence and intended to produce clinically actionable results) or secondary (exploratory) subgroup analyses (performed to inform future research). A standardized and transparent approach to HTE assessment and reporting could substantially improve clinical trial utility and interpretability

T-REX: software for the processing and analysis of T-RFLP data

Softwar

Analysis of cancer metabolism with high-throughput technologies

<p>Abstract</p> <p>Background</p> <p>Recent advances in genomics and proteomics have allowed us to study the nuances of the Warburg effect – a long-standing puzzle in cancer energy metabolism – at an unprecedented level of detail. While modern next-generation sequencing technologies are extremely powerful, the lack of appropriate data analysis tools makes this study difficult. To meet this challenge, we developed a novel application for comparative analysis of gene expression and visualization of RNA-Seq data.</p> <p>Results</p> <p>We analyzed two biological samples (normal human brain tissue and human cancer cell lines) with high-energy, metabolic requirements. We calculated digital topology and the copy number of every expressed transcript. We observed subtle but remarkable qualitative and quantitative differences between the citric acid (TCA) cycle and glycolysis pathways. We found that in the first three steps of the TCA cycle, digital expression of aconitase 2 (<it>ACO2</it>) in the brain exceeded both citrate synthase (<it>CS</it>) and isocitrate dehydrogenase 2 (<it>IDH2</it>), while in cancer cells this trend was quite the opposite. In the glycolysis pathway, all genes showed higher expression levels in cancer cell lines; and most notably, digital gene expression of glyceraldehyde-3-phosphate dehydrogenase (<it>GAPDH</it>) and enolase (<it>ENO</it>) were considerably increased when compared to the brain sample.</p> <p>Conclusions</p> <p>The variations we observed should affect the rates and quantities of ATP production. We expect that the developed tool will provide insights into the subtleties related to the causality between the Warburg effect and neoplastic transformation. Even though we focused on well-known and extensively studied metabolic pathways, the data analysis and visualization pipeline that we developed is particularly valuable as it is global and pathway-independent.</p

Stochastic Gravity: Theory and Applications

Whereas semiclassical gravity is based on the semiclassical Einstein equation with sources given by the expectation value of the stress-energy tensor of quantum fields, stochastic semiclassical gravity is based on the Einstein-Langevin equation, which has in addition sources due to the noise kernel. In the first part, we describe the fundamentals of this new theory via two approaches: the axiomatic and the functional. In the second part, we describe three applications of stochastic gravity theory. First, we consider metric perturbations in a Minkowski spacetime, compute the two-point correlation functions of these perturbations and prove that Minkowski spacetime is a stable solution of semiclassical gravity. Second, we discuss structure formation from the stochastic gravity viewpoint. Third, we discuss the backreaction of Hawking radiation in the gravitational background of a black hole and describe the metric fluctuations near the event horizon of an evaporating black holeComment: 100 pages, no figures; an update of the 2003 review in Living Reviews in Relativity gr-qc/0307032 ; it includes new sections on the Validity of Semiclassical Gravity, the Stability of Minkowski Spacetime, and the Metric Fluctuations of an Evaporating Black Hol

Description of Goussia kuehae n. sp. (Apicomplexa: Eimeriidae) infecting the Asian seabass, Lates calcarifer (Bloch)(Perciformes: Latidae), cultured in Malaysian fish farms

Culturing fishes in marine cages is a rapidly developing area of marine aquaculture. The Asian seabass Lates calcarifer (Bloch) is a fast growing good quality fish that is readily cultured in intensive systems in the South Asian region and in Malaysia in particular. Although several papers have been published to date on viral, bacterial, parasitic and fungal organisms causing diseases in the Asian seabass, the occurrence of a coccidian infection in this species has only recently been recorded. We collected sporulated and unsporulated oo¨cysts of a new species of Goussia Labbe´, 1986, from the mucus covering the epithelium of the intestine of L. calcarifer. This paper provides a description of Goussia kuehae n. sp. Sporulated oo¨cysts of this species are ellipsoidal, 37–40 lm in length and 28–30 lm in width. The ellipsoidal sporocysts are relatively small, 15.2–17 9 5.7–8 lm, and located loosely in the oo¨cyst. There are residual bodies both in the oo¨cysts and the sporocysts. Goussia kuehae n. sp. differs from all known species of Goussia in the large size of the oo¨cysts and in having two types of oo¨cyst residuum

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

PADB : Published Association Database

<p>Abstract</p> <p>Background</p> <p>Although molecular pathway information and the International HapMap Project data can help biomedical researchers to investigate the aetiology of complex diseases more effectively, such information is missing or insufficient in current genetic association databases. In addition, only a few of the environmental risk factors are included as gene-environment interactions, and the risk measures of associations are not indexed in any association databases.</p> <p>Description</p> <p>We have developed a published association database (PADB; <url>http://www.medclue.com/padb</url>) that includes both the genetic associations and the environmental risk factors available in PubMed database. Each genetic risk factor is linked to a molecular pathway database and the HapMap database through human gene symbols identified in the abstracts. And the risk measures such as odds ratios or hazard ratios are extracted automatically from the abstracts when available. Thus, users can review the association data sorted by the risk measures, and genetic associations can be grouped by human genes or molecular pathways. The search results can also be saved to tab-delimited text files for further sorting or analysis. Currently, PADB indexes more than 1,500,000 PubMed abstracts that include 3442 human genes, 461 molecular pathways and about 190,000 risk measures ranging from 0.00001 to 4878.9.</p> <p>Conclusion</p> <p>PADB is a unique online database of published associations that will serve as a novel and powerful resource for reviewing and interpreting huge association data of complex human diseases.</p

Two Plant Bacteria, S. meliloti and Ca. Liberibacter asiaticus, Share Functional znuABC Homologues That Encode for a High Affinity Zinc Uptake System

The Znu system, encoded for by znuABC, can be found in multiple genera of bacteria and has been shown to be responsible for the import of zinc under low zinc conditions. Although this high-affinity uptake system is known to be important for both growth and/or pathogenesis in bacteria, it has not been functionally characterized in a plant-associated bacterium. A single homologue of this system has been identified in the plant endosymbiont, Sinorhizobium meliloti, while two homologous systems were found in the destructive citrus pathogen, Candidatus Liberibacter asiaticus. To understand the role of these protein homologues, a complementation assay was devised allowing the individual genes that comprise the system to be assayed independently for their ability to reinstate a partially-inactivated Znu system. Results from the assays have demonstrated that although all of the genes from S. meliloti were able to restore activity, only one of the two Ca. Liberibacter asiaticus encoded gene clusters contained genes that were able to functionally complement the system. Additional analysis of the gene clusters reveals that distinct modes of regulation may also exist between the Ca. Liberibacter asiaticus and S. meliloti import systems despite the intracellular-plant niche common to both of these bacteria