A Stratified Redox Model for the Ediacaran Ocean

The Ediacaran Period (635 to 542 million years ago) was a time of fundamental environmental and evolutionary change, culminating in the first appearance of macroscopic animals. Here, we present a detailed spatial and temporal record of Ediacaran ocean chemistry for the Doushantuo Formation in the Nanhua Basin, South China. We find evidence for a metastable zone of euxinic (anoxic and sulfidic) waters impinging on the continental shelf and sandwiched within ferruginous [Fe(II)-enriched] deep waters. A stratified ocean with coeval oxic, sulfidic, and ferruginous zones, favored by overall low oceanic sulfate concentrations, was maintained dynamically throughout the Ediacaran Period. Our model reconciles seemingly conflicting geochemical redox conditions proposed previously for Ediacaran deep oceans and helps to explain the patchy temporal record of early metazoan fossils

Trees over Infinite Structures and Path Logics with Synchronization

We provide decidability and undecidability results on the model-checking problem for infinite tree structures. These tree structures are built from sequences of elements of infinite relational structures. More precisely, we deal with the tree iteration of a relational structure M in the sense of Shelah-Stupp. In contrast to classical results where model-checking is shown decidable for MSO-logic, we show decidability of the tree model-checking problem for logics that allow only path quantifiers and chain quantifiers (where chains are subsets of paths), as they appear in branching time logics; however, at the same time the tree is enriched by the equal-level relation (which holds between vertices u, v if they are on the same tree level). We separate cleanly the tree logic from the logic used for expressing properties of the underlying structure M. We illustrate the scope of the decidability results by showing that two slight extensions of the framework lead to undecidability. In particular, this applies to the (stronger) tree iteration in the sense of Muchnik-Walukiewicz.Comment: In Proceedings INFINITY 2011, arXiv:1111.267

A chemical genetic approach reveals distinct EphB signaling mechanisms during brain development.

EphB receptor tyrosine kinases control multiple steps in nervous system development. However, it remains unclear whether EphBs regulate these different developmental processes directly or indirectly. In addition, given that EphBs signal through multiple mechanisms, it has been challenging to define which signaling functions of EphBs regulate particular developmental events. To address these issues, we engineered triple knock-in mice in which the kinase activity of three neuronally expressed EphBs can be rapidly, reversibly and specifically blocked. We found that the tyrosine kinase activity of EphBs was required for axon guidance in vivo. In contrast, EphB-mediated synaptogenesis occurred normally when the kinase activity of EphBs was inhibited, suggesting that EphBs mediate synapse development by an EphB tyrosine kinase-independent mechanism. Taken together, our data indicate that EphBs control axon guidance and synaptogenesis by distinct mechanisms and provide a new mouse model for dissecting EphB function in development and disease

SETD3 is an actin histidine methyltransferase that prevents primary dystocia.

For more than 50 years, the methylation of mammalian actin at histidine 73 has been known to occur1. Despite the pervasiveness of His73 methylation, which we find is conserved in several model animals and plants, its function remains unclear and the enzyme that generates this modification is unknown. Here we identify SET domain protein 3 (SETD3) as the physiological actin His73 methyltransferase. Structural studies reveal that an extensive network of interactions clamps the actin peptide onto the surface of SETD3 to orient His73 correctly within the catalytic pocket and to facilitate methyl transfer. His73 methylation reduces the nucleotide-exchange rate on actin monomers and modestly accelerates the assembly of actin filaments. Mice that lack SETD3 show complete loss of actin His73 methylation in several tissues, and quantitative proteomics analysis shows that actin His73 methylation is the only detectable physiological substrate of SETD3. SETD3-deficient female mice have severely decreased litter sizes owing to primary maternal dystocia that is refractory to ecbolic induction agents. Furthermore, depletion of SETD3 impairs signal-induced contraction in primary human uterine smooth muscle cells. Together, our results identify a mammalian histidine methyltransferase and uncover a pivotal role for SETD3 and actin His73 methylation in the regulation of smooth muscle contractility. Our data also support the broader hypothesis that protein histidine methylation acts as a common regulatory mechanism

A Chemical Genetic Approach Reveals Distinct Mechanisms of EphB Signaling During Brain Development

EphB receptor tyrosine kinases control multiple steps in nervous system development. However, it remains unclear whether EphBs regulate these different developmental processes directly or indirectly. In addition, as EphBs signal through multiple mechanisms, it has been challenging to define which signaling functions of EphBs regulate particular developmental events. To address these issues, we engineered triple knockin mice in which the kinase activity of three neuronally expressed EphBs can be rapidly, reversibly, and specifically blocked. Using these mice we demonstrate that the tyrosine kinase activity of EphBs is required for axon guidance in vivo. By contrast, EphB-mediated synaptogenesis occurs normally when the kinase activity of EphBs is inhibited suggesting that EphBs mediate synapse development by an EphB tyrosine kinase-independent mechanism. Taken together, these experiments reveal that EphBs control axon guidance and synaptogenesis by distinct mechanisms, and provide a new mouse model for dissecting EphB function in development and disease

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

Status of Muon Collider Research and Development and Future Plans

The status of the research on muon colliders is discussed and plans are outlined for future theoretical and experimental studies. Besides continued work on the parameters of a 3-4 and 0.5 TeV center-of-mass (CoM) energy collider, many studies are now concentrating on a machine near 0.1 TeV (CoM) that could be a factory for the s-channel production of Higgs particles. We discuss the research on the various components in such muon colliders, starting from the proton accelerator needed to generate pions from a heavy-Z target and proceeding through the phase rotation and decay ($\pi \to \mu \nu_{\mu}$) channel, muon cooling, acceleration, storage in a collider ring and the collider detector. We also present theoretical and experimental R & D plans for the next several years that should lead to a better understanding of the design and feasibility issues for all of the components. This report is an update of the progress on the R & D since the Feasibility Study of Muon Colliders presented at the Snowmass'96 Workshop [R. B. Palmer, A. Sessler and A. Tollestrup, Proceedings of the 1996 DPF/DPB Summer Study on High-Energy Physics (Stanford Linear Accelerator Center, Menlo Park, CA, 1997)].Comment: 95 pages, 75 figures. Submitted to Physical Review Special Topics, Accelerators and Beam

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Fine-mapping of lipid regions in global populations discovers ethnic-specific signals and refines previously identified lipid loci

Genome-wide association studies have identified over 150 loci associated with lipid traits, however, no large-scale studies exist for Hispanics and other minority populations. Additionally, the genetic architecture of lipid-influencing loci remains largely unknown. We performed one of the most racially/ethnically diverse fine-mapping genetic studies of HDL-C, LDL-C, and triglycerides to-date using SNPs on the MetaboChip array on 54,119 individuals: 21,304 African Americans, 19,829 Hispanic Americans, 12,456 Asians, and 530 American Indians. The majority of signals found in these groups generalize to European Americans. While we uncovered signals unique to racial/ethnic populations, we also observed systematically consistent lipid associations across these groups. In African Americans, we identified three novel signals associated with HDL-C (LPL, APOA5, LCAT) and two associated with LDL-C (ABCG8, DHODH). In addition, using this population, we refined the location for 16 out of the 58 known MetaboChip lipid loci. These results can guide tailored screening efforts, reveal population-specific responses to lipid-lowering medications, and aid in the development of new targeted drug therapies

Rubber Clay Nanocomposites

The use of nanofillers allows the development of nanocomposites with improved properties and novel applications. The technological goal is possible due to the new compounding method that allows a particle dispersion in the nanometer scale increasing the specific surface area.Fil: Cova Sánchez, Mariajose. Instituto Nacional de Tecnología Industrial. Instituto Nacional de Tecnología Industrial - Caucho; Argentina. Universidad Nacional de San Martín. Instituto de Investigación e Ingeniería Ambiental. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación e Ingeniería Ambiental; ArgentinaFil: Bacigalupe, Alejandro. Universidad Nacional de San Martín. Instituto de Investigación e Ingeniería Ambiental. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigación e Ingeniería Ambiental; Argentina. Instituto Nacional de Tecnología Industrial. Instituto Nacional de Tecnología Industrial - Caucho; ArgentinaFil: Escobar, Mariano Martin. Instituto Nacional de Tecnología Industrial. Instituto Nacional de Tecnología Industrial - Caucho; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mansilla, Marcela Angela. Instituto Nacional de Tecnología Industrial. Instituto Nacional de Tecnología Industrial - Caucho; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin