Deep circulation in the Lau Basin and Havre Trough of the western South Pacific Ocean from floats and hydrography

A system of meridional ridges in the western South Pacific Ocean frame the Lau Basin and Havre Trough, and form a barrier to direct communication between the far western South Pacific basins and the interior South Pacific Ocean. The eastern side of this system comprises the Tonga and Kermadec Ridges, the location of the main deep western boundary current entering the Pacific Ocean. Observations from floats released in the Lau Basin as part of the RIDGE2000 program suggested the presence of a western boundary current along the Lau Ridge exiting into the North Fiji Basin. Those observations, together with Argo sub-surface float data and repeat hydrographic sections, confirm and expand the boundary current observations along the Lau Ridge throughout the Lau Basin and into the Havre Trough, along the Colville Ridge. The observations also reveal two previously unrecognized westward flowing jets bisecting the Lau Basin and Havre Trough. Using an extension to the classic Stommel-Arons abyssal circulation model, the predicted strength and location of these boundary currents and their bifurcation is compared with the float observations. The model provides a simplified view of the dynamics controlling the boundary current structure in the deep basins. A comparison of transport within the western boundary current derived from float data, hydrographic sections, and the idealized analytical model indicates that roughly 4 Sv (below 1,000 db) is transported northward through the Lau Basin, exiting into the North Fiji Basin

The 2010<i>M</i>_w8.8 Maule, Chile earthquake: Nucleation and rupture propagation controlled by a subducted topographic high

Knowledge of seismic properties in an earthquake rupture zone is essential for understanding the factors controlling rupture dynamics. We use data from aftershocks following the Maule earthquake to derive a three-dimensional seismic velocity model of the central Chile forearc. At 36°S, we find a highvp (&gt;7.0 km/s) and high vp/vs(?1.89) anomaly lying along the megathrust at 25 km depth, which coincides with a strong forearc Bouguer gravity signal. We interpret this as a subducted topographic high, possibly a former seamount on the Nazca slab. The Maule earthquake nucleated at the anomaly's updip boundary; yet high co-seismic slip occurred where the megathrust is overlain by lower seismic velocities. Sparse aftershock seismicity occurs within this structure, suggesting that it disrupts normal interface seismogenesis. These findings imply that subducted structures can be conducive to the nucleation of large megathrust earthquakes, even if they subsequently hinder co-seismic slip and aftershock activity

iRFP is a real time marker for transformation based assays in high content screening

Anchorage independent growth is one of the hallmarks of oncogenic transformation. Here we show that infrared fluorescent protein (iRFP) based assays allow accurate and unbiased determination of colony formation and anchorage independent growth over time. This protocol is particularly compatible with high throughput systems, in contrast to traditional methods which are often labor-intensive, subjective to bias and do not allow further analysis using the same cells. Transformation in a single layer soft agar assay could be documented as early as 2 to 3 days in a 96 well format, which can be easily combined with standard transfection, infection and compound screening setups to allow for high throughput screening to identify therapeutic targets

Pilot study on HTR2A promoter polymorphism, −1438G/A (rs6311) and a nearby copy number variation showed association with onset and severity in early onset obsessive-compulsive disorder

A previous study showed that a single nucleotide polymorphism (SNP), −1438G/A (rs6311), found in the transcriptional control region of the gene that encodes the serotonin-receptor 2A (HTR2A) was associated with obsessive-compulsive disorder (OCD) in a sample of children and adolescents. In this study, we reanalyzed the association of this SNP with OCD in an enlarged population of 136 cases (55 previous+81 new cases) and compared them to 106 newly recruited, healthy, age-matched controls. We also investigated whether this SNP or its copy number variations (CNV) was associated with OCD severity and age of onset. The CNV was analyzed in a DNA region located near rs6311. The results confirmed the association between the A-allele and early onset OCD in children and adolescents, with an odds ratio (OR) of 1.69 [95% CI (1.17, 2.46); p=0.005]. Strikingly, we found that carriers of one copy (deletion) of the CNV were associated with a very early onset OCD (2.5years earlier than the typical onset), and they had increased CY-BOCS scores (8.7 points higher compared to "normal” CNV and duplications); which is related to increased severity of OCD symptoms (p=0.031; p=0.004, respectively). Compared to the normal CNV and duplications, the association between the deletion and OCD showed an OR of 7.56 [95% CI (1.32, 142.84); p=0.020]. These results pointed to the functional importance of this promoter region of HTR2A; it influenced the occurrence, the onset, and the severity of OC

Disease modification in multiple sclerosis by flupirtine-results of a randomized placebo controlled phase II trial

Central nervous system inflammation and neurodegeneration are the pathophysiological hallmarks of multiple sclerosis (MS). While inflammation can readily be targeted by current disease modifying drugs, neurodegeneration is by far less accessible to treatment. Based on suggested additional neuroprotective capacities of the orally available non-opioid and centrally acting analgesic drug flupirtine maleate we hypothesized that treatment with flupirtine maleate might be beneficial in MS patients. The flupirtine as oral treatment in multiple sclerosis (FLORIMS) study was a multi-center, randomized and stratified, placebo-controlled double-blind phase II trial to investigate safety and efficacy in terms of clinical and radiographical activity of flupirtine maleate (300 mg per day) given orally for 12 months, add-on to interferon beta 1b subcutaneously in patients with relapsing remitting MS. Due to a substantial delay in recruitment, enrolment of patients was prematurely terminated after randomization of only 30 of the originally planned 80 patients. Of these, 24 regularly terminated study after 12 months of treatment. Data were analyzed as originally planned. Treatment with flupirtine maleate was overall well tolerated. We observed moderate and asymptomatic elevations of liver enzymes in several cases but no overt hepatotoxicity. Neither the intention to treat nor the per protocol analysis revealed any significant treatment effects of flupirtine maleate with respect to occurrence of MS relapses, disability progression, or development of new lesions on cranial MRI. However, substantial methodological limitations need to be considered when interpreting these results. In conclusion, the results of the FLORIMS study neither add further evidence to nor argue against the hypothesized neuroprotective or disease modifying effects of flupirtine maleate in MS

Power-sharing in Africa's war zones: how important is the local level?

Research on power-sharing in Africa remains silent on the effects of national peace agreements on the sub-national level. Conversely, most armed conflicts originate and are fought in (or over) specific areas. A plausible hypothesis would be that for power-sharing to have the desired pacifying effect throughout the national territory, it needs to be extended to the local level. Based on fieldwork in six former hotspots in Liberia, Burundi and the Democratic Republic of Congo (DRC) we find that there is hardly any local content, including local power-sharing, in national agreements. However, contrary to our hypothesis, neither local content (inclusion of actors or interest) nor local-power-sharing (either introducing a local power balance or monopoly) are indispensable to effectively bring about local peace, at least in the short-term. On the contrary, it might even endanger the peace process. The importance of the sub-national level is overestimated in some cases and romanticised in others. However, the history of spatial-political links, centralised policies, and the establishment of local balances or monopolies of power ultimately play an important role

(Re)configuration based on model generation

Reconfiguration is an important activity for companies selling configurable products or services which have a long life time. However, identification of a set of required changes in a legacy configuration is a hard problem, since even small changes in the requirements might imply significant modifications. In this paper we show a solution based on answer set programming, which is a logic-based knowledge representation formalism well suited for a compact description of (re)configuration problems. Its applicability is demonstrated on simple abstractions of several real-world scenarios. The evaluation of our solution on a set of benchmark instances derived from commercial (re)configuration problems shows its practical applicability.Comment: In Proceedings LoCoCo 2011, arXiv:1108.609

Towards a harmonization of distributed trait datasets

Trait-based research spans from evolutionary studies of individual-level properties to global patterns of biodiversity and ecosystem functioning. An increasing number of trait data is available for many different organism groups, being published as open access data on a variety of file hosting services. Thus, standardization between datasets is generally lacking due to heterogeneous data formats and types. The compilation of these published data into centralised databases remains a difficult and time-consuming task. We reviewed existing trait databases and online services, as well as initiatives for trait data standardization. Together with data providers and users we identified a need for a minimal trait-data terminology that is flexible enough to include traits from all types of organisms but simple enough to be adopted by different research communities. In order to facilitate reproducibility of analyses, the reuse of data and the combination of datasets from multiple sources, we propose a standardized vocabulary for trait data that is compatible with existing ontologies. We tested the vocabulary using trait datasets from several research groups working on different taxa and questions in a large project (the Biodiversity Exploratories, www.biodiversity-exploratories.de). By relying on unambiguous identifiers, the proposed minimal vocabulary for trait data captures the different degrees of resolution and measurement detail for multiple use cases of trait-based research. It further encourages the use of global Uniform Resource Identifiers (URI) for taxa and trait definitions, methods and units, thereby following the standards for a semantic web of scientific data. In addition, we developed an R-based tool to convert any trait dataset into the proposed standard format. The R-package facilitates the upload of own data to hosting services but also simplifies the access to published trait data. It also offers direct access to trait datasets that have been published in the public domain or under creative commons licenses. All these products are available through the Github platform (https://github.com/EcologicalTraitData) with the aim of a continuous collaboration and improvement with the research community. KEYWORDS: traits, standardization, ontology, semantic web, tools, distributed data, R package, Biodiversity Exploratorie

Shotgun Lipidomics Discovered Diurnal Regulation of Lipid Metabolism Linked to Insulin Sensitivity in Nondiabetic Men.

CONTEXT: Meal timing affects metabolic homeostasis and body weight, but how composition and timing of meals affect plasma lipidomics in humans is not well studied. OBJECTIVE: We used high throughput shotgun plasma lipidomics to investigate effects of timing of carbohydrate and fat intake on lipid metabolism and its relation to glycemic control. DESIGN: 29 nondiabetic men consumed (1) a high-carb test meal (MTT-HC) at 09.00 and a high-fat meal (MTT-HF) at 15.40; or (2) MTT-HF at 09.00 and MTT-HC at 15.40. Blood was sampled before and 180 minutes after completion of each MTT. Subcutaneous adipose tissue (SAT) was collected after overnight fast and both MTTs. Prior to each investigation day, participants consumed a 4-week isocaloric diet of the same composition: (1) high-carb meals until 13.30 and high-fat meals between 16.30 and 22:00 or (2) the inverse order. RESULTS: 12 hour daily lipid patterns showed a complex regulation by both the time of day (67.8%) and meal composition (55.4%). A third of lipids showed a diurnal variation in postprandial responses to the same meal with mostly higher responses in the morning than in the afternoon. Triacylglycerols containing shorter and more saturated fatty acids were enriched in the morning. SAT transcripts involved in fatty acid synthesis and desaturation showed no diurnal variation. Diurnal changes of 7 lipid classes were negatively associated with insulin sensitivity, but not with glucose and insulin response or insulin secretion. CONCLUSIONS: This study identified postprandial plasma lipid profiles as being strongly affected by meal timing and associated with insulin sensitivity

Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity

Trained innate immunity fosters a sustained favorable response of myeloid cells to a secondary challenge, despite their short lifespan in circulation. We thus hypothesized that trained immunity acts via modulation of hematopoietic stem and progenitor cells (HSPCs). Administration of β-glucan (prototypical trained-immunity-inducing agonist) to mice induced expansion of progenitors of the myeloid lineage, which was associated with elevated signaling by innate immune mediators, such as IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF), and with adaptations in glucose metabolism and cholesterol biosynthesis. The trained-immunity-related increase in myelopoiesis resulted in a beneficial response to secondary LPS challenge and protection from chemotherapy-induced myelosuppression in mice. Therefore, modulation of myeloid progenitors in the bone marrow is an integral component of trained immunity, which to date, was considered to involve functional changes of mature myeloid cells in the periphery