Modeling Challenging EMC Problems Using the Method of Moments

A variety of numerical techniques are used in electromagnetic compatibility (EMC) for the numerical analysis of practical problems. The most important are the finite-difference time-domain technique, the finite-element method, the transmission-line-matrix method and the method of moments. All approaches have their strengths and weaknesses and cannot be applied to all kinds of problems with the same degree of efficiency, measured in memory consumption and computation time necessary. In this paper it is shown that the method of moments (MoM) can be applied to a variety of scenarios, each of which would form a challenging problem to all of the mentioned numerical techniques. It is shown that a customization of the MoM to the specific problems at hand can be accomplished. All examples shown have been computed using the academic code CONCEPT-II developed at Hamburg University of Technology (TUHH)

Multiple nearest-neighbor exchange model for the frustrated magnetic molecules Mo72Fe30 and Mo72Cr30

Our measurements of the differential susceptibility dM/dH of the frustrated magnetic molecules Mo72Fe30 and Mo72Cr30 reveal a pronounced dependence on magnetic field (H) and temperature (T) in the low H - low T regime, contrary to the predictions of existing models. Excellent agreement with experiment is achieved upon formulating a nearest-neighbor classical Heisenberg model where the 60 nearest-neighbor exchange interactions in each molecule, rather than being identical as has been assumed heretofore, are described by a two-parameter probability distribution of values of the exchange constant. We suggest that the probability distribution provides a convenient phenomenological platform for summarizing the combined effects of multiple microscopic mechanisms that disrupt the idealized picture of a Heisenberg model based on a single value of the nearest-neighbor exchange constant.Comment: 8 pages, 5 figure

Effects of Compressive and Tensile Strain on Macrophages during Simulated Orthodontic Tooth Movement

During orthodontic tooth movement (OTM) to therapeutically correct the position of misaligned teeth, thus improving oral health and quality of life, fibroblasts, macrophages, and other immune cells within the periodontal ligament (PDL), which connects a tooth to its surrounding bone, are exposed to compressive and tensile strain. While it is known that PDL fibroblasts are critically involved in the biological regulation of OTM by a mechanotransductively triggered release of cytokines, it is unclear whether macrophages also react to pressure and tension in a similar manner thus impacting on or mediating OTM. RAW264.7 macrophages were seeded onto conventional 6-well cell culture plates for pressure or on Bioflex plates for tension assays and preincubated for 24 h. For in vitro simulation of physiological orthodontic compressive or tensile strain for 2 h, 4 h, 24 h, and 48 h, glass discs (2 g/cm(2)) were placed or adherent macrophages isotropically stretched for 16%, respectively. We determined cell number, cytotoxicity, and gene/protein expression of Vegf-a/VEGF-A (macrophage-mediated angiogenesis), Mmp-8/9 (extracellular matrix reorganization), and Cox-2/PG-E2, Il-6/IL-6, and Tnf-alpha/TNF-alpha (proinflammatory mediators) by RT-qPCR and ELISA. Compressive but not tensile strain resulted in a significant reduction in cell number after only 2 h. Mmp-8 and Mmp-9 expression was significantly enhanced within 24 h of compressive and in part tensile strain. Significantly increased Vegf-a/VEGF-A expression was detected within 4 h of pressure, but not during application of tensile strain. Expression of proinflammatory mediators Cox-2/PG-E2, Il-6/IL-6, and Tnf-alpha/TNF-alpha was significantly increased as early as 2-4 h after application of compressive or tensile strain. Our results indicate that macrophages respond early on to compressive and tensile strain occurring during OTM with an enhanced gene expression of proinflammatory cytokines, which could affect PDL fibroblasts, osteoblasts, and immune cells triggering or enhancing the biological mechanisms and osteoclastogenesis underlying OTM

Impact of salt and the osmoprotective transcription factor NFAT-5 on macrophages during mechanical strain

Myeloid cells regulate bone density in response to increased salt (NaCl) intake via the osmoprotective transcription factor, nuclear factor of activated T cells-5 (NFAT-5). Because orthodontic tooth movement (OTM) is a pseudoinflammatory immunological process, we investigated the influence of NaCl and NFAT-5 on the expression pattern of macrophages in a model of simulated OTM. RAW264.7 macrophages were exposed for 4 h to 2 ⁻²g cm compressive or 16% tensile or no mechanical strain (control), with or without the addition of 40 mM NaCl. We analyzed the expression of inflammatory genes and proteins [tumor necrosis factor (TNF), interleukin (IL)-6 and prostaglandin endoperoxide synthase-2 (Ptgs-2)/prostaglandin E2 (PG-E2)] by real-time-quantitative PCR and ELISA. To investigate the role of NFAT-5 in these responses, NFAT-5 was both constitutively expressed and silenced. Salt and compressive strain, but not tensile strain increased the expression of NFAT-5 and most tested inflammatory factors in macrophages. NaCl induced the expression of Ptgs-2/PG-E2 and TNF, whereas secretion of IL-6 was inhibited. Similarly, a constitutive expression of NFAT-5 reduced IL-6 expression, while increasing Ptgs-2/PG-E2 and TNF expression. Silencing of NFAT-5 upregulated IL-6 and reduced Ptgs-2/PG-E2 and TNF expression. Salt had an impact on the expression profile of macrophages as a reaction to compressive and tensile strain that occur during OTM. This was mediated via NFAT-5, which surprisingly also seems to play a regulatory role in mechanotransduction of compressive strain. Sodium accumulation in the periodontal ligament caused by dietary salt consumption might propagate local osteoclastogenesis via increased local inflammation and thus OTM velocity, but possibly also entail side effects such as dental root resorptions or periodontal bone loss

High susceptibility to fatty liver disease in two-pore channel 2-deficient mice

Endolysosomal organelles play a key role in trafficking, breakdown and receptor-mediated recycling of different macromolecules such as low-density lipoprotein (LDL)-cholesterol, epithelial growth factor (EGF) or transferrin. Here we examine the role of two-pore channel (TPC) 2, an endolysosomal cation channel, in these processes. Embryonic mouse fibroblasts and hepatocytes lacking TPC2 display a profound impairment of LDL-cholesterol and EGF/EGF-receptor trafficking. Mechanistically, both defects can be attributed to a dysfunction of the endolysosomal degradation pathway most likely on the level of late endosome to lysosome fusion. Importantly, endolysosomal acidification or lysosomal enzyme function are normal in TPC2-deficient cells. TPC2-deficient mice are highly susceptible to hepatic cholesterol overload and liver damage consistent with non-alcoholic fatty liver hepatitis. These findings indicate reduced metabolic reserve of hepatic cholesterol handling. Our results suggest that TPC2 plays a crucial role in trafficking in the endolysosomal degradation pathway and, thus, is potentially involved in the homoeostatic control of many macromolecules and cell metabolites

Characterization and petrologic interpretation of olivine-rich basalts at Gusev Crater, Mars

Rocks on the floor of Gusev crater are basalts of uniform composition and mineralogy. Olivine, the only mineral to have been identified or inferred from data by all instruments on the Spirit rover, is especially abundant in these rocks. These picritic basalts are similar in many respects to certain Martian meteorites (olivine-phyric shergottites). The olivine megacrysts in both have intermediate compositions, with modal abundances ranging up to 20–30%. Associated minerals in both include low-calcium and highcalcium pyroxenes, plagioclase of intermediate composition, iron-titanium-chromium oxides, and phosphate. These rocks also share minor element trends, reflected in their nickel-magnesium and chromium-magnesium ratios. Gusev basalts and shergottites appear to have formed from primitive magmas produced by melting an undepleted mantle at depth and erupted without significant fractionation. However, apparent differences between Gusev rocks and shergottites in their ages, plagioclase abundances, and volatile contents preclude direct correlation. Orbital determinations of global olivine distribution and compositions by thermal emission spectroscopy suggest that olivine-rich rocks may be widespread. Because weathering under acidic conditions preferentially attacks olivine and disguises such rocks beneath alteration rinds, picritic basalts formed from primitive magmas may even be a common component of the Martian crust formed during ancient and recent times.Additional co-authors: PR Christensen, BC Clark, JA Crisp, DJ DesMarais, T Economou, JD Farmer, W Farrand, A Ghosh, M Golombek, S Gorevan, R Greeley, VE Hamilton, JR Johnson, BL Joliff, G Klingelhöfer, AT Knudson, S McLennan, D Ming, JE Moersch, R Rieder, SW Ruff, PA de Souza Jr, SW Squyres, H Wnke, A Wang, A Yen, J Zipfe

HLA-DPA1*02:01~B1*01:01 is a risk haplotype for primary sclerosing cholangitis mediating activation of NKp44+ NK cells

Objective Primary sclerosing cholangitis (PSC) is characterised by bile duct strictures and progressive liver disease, eventually requiring liver transplantation. Although the pathogenesis of PSC remains incompletely understood, strong associations with HLA-class II haplotypes have been described. As specific HLA-DP molecules can bind the activating NK-cell receptor NKp44, we investigated the role of HLA-DP/NKp44-interactions in PSC. Design Liver tissue, intrahepatic and peripheral blood lymphocytes of individuals with PSC and control individuals were characterised using flow cytometry, immunohistochemical and immunofluorescence analyses. HLA-DPA1 and HLA-DPB1 imputation and association analyses were performed in 3408 individuals with PSC and 34 213 controls. NK cell activation on NKp44/HLA-DP interactions was assessed in vitro using plate-bound HLA-DP molecules and HLA-DPB wildtype versus knock-out human cholangiocyte organoids. Results NKp44+NK cells were enriched in livers, and intrahepatic bile ducts of individuals with PSC showed higher expression of HLA-DP. HLA-DP haplotype analysis revealed a highly elevated PSC risk for HLA-DPA1*02:01~B1*01:01 (OR 1.99, p=6.7×10-50). Primary NKp44+NK cells exhibited significantly higher degranulation in response to plate-bound HLA-DPA1*02:01-DPB1*01:01 compared with control HLA-DP molecules, which were inhibited by anti-NKp44-blocking. Human cholangiocyte organoids expressing HLA-DPA1*02:01-DPB1*01:01 after IFN-γ-exposure demonstrated significantly increased binding to NKp44-Fc constructs compared with unstimulated controls. Importantly, HLA-DPA1*02:01-DPB1*01:01-expressing organoids increased degranulation of NKp44+NK cells compared with HLA-DPB1-KO organoids. Conclusion Our studies identify a novel PSC risk haplotype HLA-DP A1*02:01~DPB1*01:01 and provide clinical and functional data implicating NKp44+NK cells that recognise HLA-DPA1*02:01-DPB1*01:01 expressed on cholangiocytes in PSC pathogenesis

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory

The Auger Engineering Radio Array (AERA) is part of the Pierre Auger Observatory and is used to detect the radio emission of cosmic-ray air showers. These observations are compared to the data of the surface detector stations of the Observatory, which provide well-calibrated information on the cosmic-ray energies and arrival directions. The response of the radio stations in the 30 to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of the incoming electric field. For the latter, the energy deposit per area is determined from the radio pulses at each observer position and is interpolated using a two-dimensional function that takes into account signal asymmetries due to interference between the geomagnetic and charge-excess emission components. The spatial integral over the signal distribution gives a direct measurement of the energy transferred from the primary cosmic ray into radio emission in the AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air shower arriving perpendicularly to the geomagnetic field. This radiation energy -- corrected for geometrical effects -- is used as a cosmic-ray energy estimator. Performing an absolute energy calibration against the surface-detector information, we observe that this radio-energy estimator scales quadratically with the cosmic-ray energy as expected for coherent emission. We find an energy resolution of the radio reconstruction of 22% for the data set and 17% for a high-quality subset containing only events with at least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO