Parallel Smoothers for Matrix-based Multigrid Methods on Unstructured Meshes Using Multicore CPUs and GPUs

Multigrid methods are efficient and fast solvers for problems typically modeled by partial differential equations of elliptic type. For problems with complex geometries and local singularities stencil-type discrete operators on equidistant Cartesian grids need to be replaced by more flexible concepts for unstructured meshes in order to properly resolve all problem-inherent specifics and for maintaining a moderate number of unknowns. However, flexibility in the meshes goes along with severe drawbacks with respect to parallel execution – especially with respect to the definition of adequate smoothers. This point becomes in particular pronounced in the framework of fine-grained parallelism on GPUs with hundreds of execution units. We use the approach of matrixbased multigrid that has high flexibility and adapts well to the exigences of modern computing platforms. In this work we investigate multi-colored Gauß-Seidel type smoothers, the power(q)-pattern enhanced multi-colored ILU(p) smoothers with fillins

Combining mass spectrometry and genetic labeling in mice to report TRP channel expression

Transient receptor potential (TRP) ion channels play important roles in fundamental biological processes throughout the body of humans and mice. TRP channel dysfunction manifests in different disease states, therefore, these channels may represent promising therapeutic targets in treating these conditions. Many TRP channels are expressed in several organs suggesting multiple functions and making it challenging to untangle the systemic pathophysiology of TRP dysfunction. Detailed characterization of the expression pattern of the individual TRP channels throughout the organism is thus essential to interpret data such as those derived from systemic phenotyping of global TRP knockout mice. Murine TRP channel reporter strains enable reliable labeling of TRP expression with a fluorescent marker. Here we present an optimized method to visualize primary TRP-expressing cells with single cell resolution throughout the entire organism. In parallel, we methodically combine systemic gene expression profiling with an adjusted mass spectrometry protocol to document acute protein levels in selected organs of interest. The TRP protein expression data are then correlated with the GFP reporter expression data. The combined methodological approach presented here can be adopted to generate expression data for other genes of interest and reporter mice. • We present an optimized method to systemically characterize gene expression in fluorescent reporter mouse strains with a single cell resolution. • We methodically combine systemic gene expression profiling with an adjusted mass spectrometry protocol to document acute protein levels in selected organs of interest in mice

Control of Insulin Release by Transient Receptor Potential Melastatin 3 (TRPM3) Ion Channels

Background/Aims: The release of insulin in response to increased levels of glucose in the blood strongly depends on Ca2+ influx into pancreatic beta cells by the opening of voltage-gated Ca2+ channels. Transient Receptor Potential Melastatin 3 proteins build Ca2+ permeable, non-selective cation channels serving as pain sensors of noxious heat in the peripheral nervous system. TRPM3 channels are also strongly expressed in pancreatic beta cells that respond to the TRPM3 agonist pregnenolone sulfate with Ca2+ influx and increased insulin release. Therefore, we hypothesized that in beta cells TRPM3 channels may contribute to pregnenolone sulfate- as well as to glucose-induced insulin release. Methods: We used INS-1 cells as a beta cell model in which we analysed the occurrence of TRPM3 isoformes by immunoprecipitation and western blotting and by cloning of RT-PCR amplified cDNA fragments. We applied pharmacological as well as CRISPR/Cas9-based strategies to analyse the interplay of TRPM3 and voltage-gated Ca2+ channels in imaging experiments (FMP, Fura-2) and electrophysiological recordings. In immunoassays, we examined the contribution of TRPM3 channels to pregnenolone sulfate- and glucose-induced insulin release. To confirm our findings, we generated beta cell-specific Trpm3-deficient mice and compared their glucose clearance with the wild type in glucose tolerance tests. Results: TRPM3 channels triggered the activity of voltage-gated Ca2+ channels and both channels together contributed to insulin release after TRPM3 activation. Trpm3-deficient INS-1 cells lacked pregnenolone sulfate-induced Ca2+ signals just like the pregnenolone sulfate-induced insulin release. Both, glucose-induced Ca2+ signals and the glucose-induced insulin release were strongly reduced. Accordingly, Trpm3-deficient mice displayed an impaired decrease of the blood sugar concentration after intraperitoneal or oral administration of glucose. Conclusion: The present study suggests an important role for TRPM3 channels in the control of glucose-dependent insulin release

Transient Receptor Potential Vanilloid 6 (TRPV6) Proteins Control the Extracellular Matrix Structure of the Placental Labyrinth

Calcium-selective transient receptor potential Vanilloid 6 (TRPV6) channels are expressed in fetal labyrinth trophoblasts as part of the feto–maternal barrier, necessary for sufficient calcium supply, embryo growth, and bone development during pregnancy. Recently, we have shown a less- compact labyrinth morphology of Trpv6-deficient placentae, and reduced Ca2+ uptake of primary trophoblasts upon functional deletion of TRPV6. Trpv6-/- trophoblasts show a distinct calcium-dependent phenotype. Deep proteomic profiling of wt and Trpv6-/- primary trophoblasts using label-free quantitative mass spectrometry leads to the identification of 2778 proteins. Among those, a group of proteases, including high-temperature requirement A serine peptidase 1 (HTRA1) and different granzymes are more abundantly expressed in Trpv6-/- trophoblast lysates, whereas the extracellular matrix protein fibronectin and the fibronectin-domain-containing protein 3A (FND3A) were markedly reduced. Trpv6-/- placenta lysates contain a higher intrinsic proteolytic activity increasing fibronectin degradation. Our results show that the extracellular matrix formation of the placental labyrinth depends on TRPV6; its deletion in trophoblasts correlates with the increased expression of proteases controlling the extracellular matrix in the labyrinth during pregnancy

Ovulation is triggered by a cyclical modulation of gonadotropes into a hyperexcitable state

Gonadotropes in the anterior pituitary gland are essential for fertility and provide a functional link between the brain and the gonads. To trigger ovulation, gonadotrope cells release massive amounts of luteinizing hormone (LH). The mechanism underlying this remains unclear. Here, we utilize a mouse model expressing a genetically encoded Ca2+ indicator exclusively in gonadotropes to dissect this mechanism in intact pituitaries. We demonstrate that female gonadotropes exclusively exhibit a state of hyperexcitability during the LH surge, resulting in spontaneous [Ca2+]i transients in these cells, which persist in the absence of any in vivo hormonal signals. L-type Ca2+ channels and transient receptor potential channel A1 (TRPA1) together with intracellular reactive oxygen species (ROS) levels ensure this state of hyperexcitability. Consistent with this, virus-assisted triple knockout of Trpa1 and L-type Ca2+ subunits in gonadotropes leads to vaginal closure in cycling females. Our data provide insight into molecular mechanisms required for ovulation and reproductive success in mammals

Simulation of the Maximum Throughput of an Autostore-Storage System

Autostore-Lagersysteme (RCS/RS) sind vollautomatische Behälter-Kleinteilelager, die durch Roboter von oben bedient werden. Diese lagern Kunststoffbehälter gestapelt übereinander, wodurch innerhalb des Stapels die Lagerstrategie ‚Last-In-First-Out‘ Anwendung findet. Werden weiter unten befindliche Behälter benötigt, lagern die Roboter zuvor weiter oben befindliche Behälter um. Neben den Systemparametern gibt es zahlreiche weitere Faktoren, wie beispielsweise die Anzahl an Robotern und Kommissionierstationen oder die Rastergröße, die das Systemverhalten wesentlich mitbeeinflussen. Mit einer ereignisdiskreten Simulation wurden Erkenntnisse zu möglichen Auslegungsvarianten und Betriebsweisen gewonnen. Die Resultate zeigen den Einfluss der Anzahl an Robotern auf die Umschlagleistung derartiger Lagersysteme.Robotbased compact storage and retrieval systems (RCS/RS) such as the Autostore-system are fully-automatic operated by robots from above. The goods are stored in plastic bins that are stacked on top of each other, applying the 'Last-In-First-Out' storage strategy within the stack. If containers located further down are required, the robots relocate them. In addition to the system parameters, there are numerous other factors, such as the number of used robots or picking stations, that influence the system behavior. With an event-discrete simulation in the Simio simulation program, insights into possible design variants and operating modes were gained. The number of robots has a large impact on the throughput of an Autostore-system

Genome Sequence of Paracoccus contaminans LMG 29738T, Isolated from a Water Microcosm

We announce here the complete genome sequence of Paracoccus contaminans LMG 29738T, which we recently isolated from a contaminated water microcosm. The genome consists of a 2.94-Mb chromosome and a 94-kb plasmid. To our knowledge, we provide the first DNA methylation analysis of a Paracoccus species

A novel calibration method for digital templating of total hip arthroplasty: a prospective clinical study of dual scale type single marker calibration in supine radiographs

Background External calibration markers (ECM) are the standard of care for digital templating in joint replacements. Spherical mono markers are known to be unreliable. Fixed calibration factors (FCF) can reduce the overall error by placement of markers, but do not address individual patient anatomy. Dual scale calibration marker (DSCM) methods were developed to improve precision of calibration but require two markers. This prospective observational study is the first to analyse the application of a dual scale type single marker (DSSM) method in supine radiographs. Methods One hundred patients with unilateral total hip arthroplasty (THA) underwent anterior-posterior pelvis X-ray with ECM and DSSM. The femoral THA head components were used as internal reference (ICM). An empirical fixed calibration factor (FCF; 120%) was used as comparator. Absolute differences of ICM and both ECM and DSSM were calculated. Absolute relative deviations (ARD) were calculated. Results Mean absolute calibration factor differences of ECM, FCF and DSSM from ICM were 0.105 (0.002-0.182), 0.016 (0.082-0.013) and 0.011 (0.056-0.009), respectively. ARD differences between ECM and DSSM as well as FCF and DSSM were significant (p < 0.001). Conclusion The DSSM method showed superior results over ECM and FCF to predict the optimal calibration factor in supine radiographs. The novel DSSM method could be used to improve digital templating in supine radiographs without need for additional markers