A 3-D Track-Finding Processor for the CMS Level-1 Muon Trigger

We report on the design and test results of a prototype processor for the CMS Level-1 trigger that performs 3-D track reconstruction and measurement from data recorded by the cathode strip chambers of the endcap muon system. The tracking algorithms are written in C++ using a class library we developed that facilitates automatic conversion to Verilog. The code is synthesized into firmware for field-programmable gate-arrays from the Xilinx Virtex-II series. A second-generation prototype has been developed and is currently under test. It performs regional track-finding in a 60 degree azimuthal sector and accepts 3 GB/s of input data synchronously with the 40 MHz beam crossing frequency. The latency of the track-finding algorithms is expected to be 250 ns, including geometrical alignment correction of incoming track segments and a final momentum assignment based on the muon trajectory in the non-uniform magnetic field in the CMS endcaps.Comment: 7 pages, 5 figures, proceedings for the conference on Computing in High Energy and Nuclear Physics, March 24-28 2003, La Jolla, Californi

Pathology and advanced imaging – characterization of a congenital cardiac defect and complex hemodynamics in a pig: A case report

Domestic pigs are widely used in cardiovascular research as the porcine circulatory system bears a remarkable resemblance to that of humans. In order to reduce variability, only clinically healthy animals enter the study as their health status is assessed in entry examination. Like humans, pigs can also suffer from congenital heart disease, such as an atrial septal defect (ASD), which often remains undetected. Due to the malformation of the endocardial cushion during organ development, mitral valve defects (e.g., mitral clefts) are sometimes associated with ASDs, further contributing to hemodynamic instability. In this work, we report an incidental finding of a hemodynamically highly relevant ASD in the presence of incompetent mitral and tricuspid valves, in an asymptomatic, otherwise healthy juvenile pig. In-depth characterization of the cardiac blood flow by four-dimensional (4D) flow magnetic resonance imaging (MRI) revealed a prominent diastolic left-to-right and discrete systolic right-to-left shunt, resulting in a pulmonary-to-systemic flow ratio of 1.8. Severe mitral (15 mL/stroke) and tricuspid (22 mL/stroke) regurgitation further reduced cardiac output. Pathological examination confirmed the presence of an ostium primum ASD and found a serous cyst of lymphatic origin that was filled with clear fluid partially occluding the ASD. A large mitral cleft was identified as the most likely cause of severe regurgitation, and histology showed mild to moderate endocardiosis in the coaptation area of both atrio-ventricular valves. In summary, although not common, congenital heart defects could play a role as a cause of experimental variability or even intra-experimental mortality when working with apparently heathy, juvenile pigs

Regulation of neuroD2 expression in mouse brain

AbstractThe basic helix–loop–helix (bHLH) transcription factor, neuroD2, induces neuronal differentiation and promotes neuronal survival. Reduced levels of neuroD2 were previously shown to cause motor deficits, ataxia, and seizure propensity. Because neuroD2 levels may be critical for brain function, we studied the regulation of neuroD2 gene in cell culture and transgenic mouse models. In transgenic mice, a 10-kb fragment of the neuroD2 promoter fully recapitulated the endogenous neuroD2 staining pattern. A 1-kb fragment of the neuroD2 promoter drove reporter gene expression in most, but not all neuroD2-positive neuronal populations. Mutation of two critical E-boxes, E4 and E5 (E4 and E5 situated 149 and 305 bp upstream of the transcriptional start site) eliminated gene expression. NeuroD2 expression was diminished in mice lacking neurogenin1 demonstrating that neurogenin1 regulates neuroD2 during murine brain development. These studies demonstrate that neuroD2 expression is highly dependent on bHLH-responsive E-boxes in the proximal promoter region, that additional distal regulatory elements are important for neuroD2 expression in a subset of cortical neurons, and that neurogenin1 regulates neuroD2 expression during mouse brain development

Protistan community patterns within the brine and halocline of deep hypersaline anoxic basins in the eastern Mediterranean Sea

Author Posting. © The Author(s), 2008. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Extremophiles 13 (2009): 151-167, doi:10.1007/s00792-008-0206-2.Environmental factors restrict the distribution of microbial eukaryotes but the exact boundaries for eukaryotic life are not known. Here we examine protistan communities at the extremes of salinity and osmotic pressure, and report rich assemblages inhabiting Bannock and Discovery, two deep-sea superhaline anoxic basins in the Mediterranean. Using a rRNA-based approach, we detected 1538 protistan rRNA gene sequences from water samples with total salinity ranging from 39 g/kg to 280 g/Kg, and obtained evidence that this DNA was endogenous to the extreme habitats sampled. Statistical analyses indicate that the discovered phylotypes represent only a fraction of species actually inhabiting both the brine and the brine-seawater interface, with as much as 82% of the actual richness missed by our survey. Jaccard indices (e.g., for a comparison of community membership) suggest that the brine/interface protistan communities are unique to Bannock and Discovery basins, and share little (0.8-2.8%) in species composition with overlying waters with typical marine salinity and oxygen tension. The protistan communities from the basins’ brine and brine/seawater interface appear to be particularly enriched with dinoflagellates, ciliates and other alveolates, as well as fungi, and are conspicuously poor in stramenopiles. The uniqueness and diversity of brine and brine-interface protistan communities make them promising targets for protistan discovery.This study was supported by grant grant STO414/2-4 of the Deutsche Forschungsgemeinschaft, the EuroDEEP program of the European Science Foundation under 06-EuroDEEP-FP-004 MIDDLE project and NSF-grant MCB- 034834

Identification of PBX1 Target Genes in Cancer Cells by Global Mapping of PBX1 Binding Sites

PBX1 is a TALE homeodomain transcription factor involved in organogenesis and tumorigenesis. Although it has been shown that ovarian, breast, and melanoma cancer cells depend on PBX1 for cell growth and survival, the molecular mechanism of how PBX1 promotes tumorigenesis remains unclear. Here, we applied an integrated approach by overlapping PBX1 ChIP-chip targets with the PBX1-regulated transcriptome in ovarian cancer cells to identify genes whose transcription was directly regulated by PBX1. We further determined if PBX1 target genes identified in ovarian cancer cells were co-overexpressed with PBX1 in carcinoma tissues. By analyzing TCGA gene expression microarray datasets from ovarian serous carcinomas, we found co-upregulation of PBX1 and a significant number of its direct target genes. Among the PBX1 target genes, a homeodomain protein MEOX1 whose DNA binding motif was enriched in PBX1-immunoprecipicated DNA sequences was selected for functional analysis. We demonstrated that MEOX1 protein interacts with PBX1 protein and inhibition of MEOX1 yields a similar growth inhibitory phenotype as PBX1 suppression. Furthermore, ectopically expressed MEOX1 functionally rescued the PBX1-withdrawn effect, suggesting MEOX1 mediates the cellular growth signal of PBX1. These results demonstrate that MEOX1 is a critical target gene and cofactor of PBX1 in ovarian cancers

Evidence for isolated evolution of deep-sea ciliate communities through geological separation and environmental selection

© The Author(s), 2013. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in BMC Microbiology 13 (2013): 150, doi:10.1186/1471-2180-13-150.Deep hypersaline anoxic basins (DHABs) are isolated habitats at the bottom of the eastern Mediterranean Sea, which originate from the ancient dissolution of Messinian evaporites. The different basins have recruited their original biota from the same source, but their geological evolution eventually constituted sharp environmental barriers, restricting genetic exchange between the individual basins. Therefore, DHABs are unique model systems to assess the effect of geological events and environmental conditions on the evolution and diversification of protistan plankton. Here, we examine evidence for isolated evolution of unicellular eukaryote protistan plankton communities driven by geological separation and environmental selection. We specifically focused on ciliated protists as a major component of protistan DHAB plankton by pyrosequencing the hypervariable V4 fragment of the small subunit ribosomal RNA. Geospatial distributions and responses of marine ciliates to differential hydrochemistries suggest strong physical and chemical barriers to dispersal that influence the evolution of this plankton group. Ciliate communities in the brines of four investigated DHABs are distinctively different from ciliate communities in the interfaces (haloclines) immediately above the brines. While the interface ciliate communities from different sites are relatively similar to each other, the brine ciliate communities are significantly different between sites. We found no distance-decay relationship, and canonical correspondence analyses identified oxygen and sodium as most important hydrochemical parameters explaining the partitioning of diversity between interface and brine ciliate communities. However, none of the analyzed hydrochemical parameters explained the significant differences between brine ciliate communities in different basins. Our data indicate a frequent genetic exchange in the deep-sea water above the brines. The “isolated island character” of the different brines, that resulted from geological events and contemporary environmental conditions, create selective pressures driving evolutionary processes, and with time, lead to speciation and shape protistan community composition. We conclude that community assembly in DHABs is a mixture of isolated evolution (as evidenced by small changes in V4 primary structure in some taxa) and species sorting (as indicated by the regional absence/presence of individual taxon groups on high levels in taxonomic hierarchy).This work was funded by NSF grants OCE-0849578 and OCE- 1061774 to VE and support from Carl Zeiss fellowship to AS and from the Deutsche Forschungsgemeinschaft (grants STO414/3-2 and STO414/7-1) to TS

Search for B^0-> p p-bar, Lambda Lambda-bar and B^+ -> p Lambda-bar at Belle

We report on a new search for two-body baryonic decays of the B meson. Improved sensitivity compared to previous Belle results is obtained from 414 fb^-1 of data that corresponds to 449 million B B-bar pairs, which were taken on the Upsilon(4S) resonance and collected with the Belle detector at the KEKB e^+e^- collider. No significant signals are observed and we set the 90% confidence level upper limits: Br(B^0-> p pbar) Lambda Lambda-bar) p Lambda-bar) < 3.2X10^-7.Comment: 5 pages, 2 figures, submitted to PR

Measurements of exclusive B_s^0 decays at the Y(5S) resonance

Several exclusive $B_s^0$ decays are studied using a 1.86 fb-1 data sample collected at the Y(5S) resonance with the Belle detector at the KEKB asymmetric energy e^+ e^- collider. In the $B_s^0 \to D_s^- \pi^+$ decay mode we find 10 $B_s^0$ candidates and measure the corresponding branching fraction. Combining the B_s^0 -> D_s^{(*)-} \pi^+, B_s^0 -> D_s^{(*)-} \rho^+, B_s^0 -> J/\psi \phi and B_s^0 -> J/\psi \eta decay modes, a significant $B_s^0$ signal is observed. The ratio \sigma (e^+ e^- -> B_s^* \bar{B}_s^*) / \sigma (e^+ e^- -> B_s^{(*)} \bar{B}_s^{(*)}) = (93^{+7}_{-9} \pm 1)% is obtained at the Y(5S) energy, indicating that $B_s^0$ meson production proceeds predominantly through the creation of $B^*_s \bar{B}^*_s$ pairs. The $B_s^0$ and $B_s^*$ meson masses are measured to be M(B_s^0)=(5370 \pm 1 \pm 3)MeV/c^2 and M(B_s^*)=(5418 \pm 1 \pm 3)MeV/c^2. Upper limits on the B_s^0 -> \gamma \gamma, B_s^0 -> \phi \gamma, B_s^0 -> K^+ K^- and B_s^0 -> D_s^{(*)+} D_s^{(*)-} branching fractions are also reported.Comment: 9 pages, 5 figures, published in Phys. Rev. D76, 012002 (2007

Uncultivated Microbial Eukaryotic Diversity: A Method to Link ssu rRNA Gene Sequences with Morphology

Protists have traditionally been identified by cultivation and classified taxonomically based on their cellular morphologies and behavior. In the past decade, however, many novel protist taxa have been identified using cultivation independent ssu rRNA sequence surveys. New rRNA “phylotypes” from uncultivated eukaryotes have no connection to the wealth of prior morphological descriptions of protists. To link phylogenetically informative sequences with taxonomically informative morphological descriptions, we demonstrate several methods for combining whole cell rRNA-targeted fluorescent in situ hybridization (FISH) with cytoskeletal or organellar immunostaining. Either eukaryote or ciliate-specific ssu rRNA probes were combined with an anti-α-tubulin antibody or phalloidin, a common actin stain, to define cytoskeletal features of uncultivated protists in several environmental samples. The eukaryote ssu rRNA probe was also combined with Mitotracker® or a hydrogenosomal-specific anti-Hsp70 antibody to localize mitochondria and hydrogenosomes, respectively, in uncultivated protists from different environments. Using rRNA probes in combination with immunostaining, we linked ssu rRNA phylotypes with microtubule structure to describe flagellate and ciliate morphology in three diverse environments, and linked Naegleria spp. to their amoeboid morphology using actin staining in hay infusion samples. We also linked uncultivated ciliates to morphologically similar Colpoda-like ciliates using tubulin immunostaining with a ciliate-specific rRNA probe. Combining rRNA-targeted FISH with cytoskeletal immunostaining or stains targeting specific organelles provides a fast, efficient, high throughput method for linking genetic sequences with morphological features in uncultivated protists. When linked to phylotype, morphological descriptions of protists can both complement and vet the increasing number of sequences from uncultivated protists, including those of novel lineages, identified in diverse environments