BCL11B regulates arterial stiffness and related target organ damage

RATIONALE: BCL11B (B-cell leukemia 11b) is a transcription factor known as an essential regulator of T lymphocytes and neuronal development during embryogenesis. A genome-wide association study showed that a gene desert region downstream of BCL11B, known to function as a BCL11B enhancer, harbors single nucleotide polymorphisms associated with increased arterial stiffness. However, a role for BCL11B in the adult cardiovascular system is unknown. OBJECTIVE: Based on these human findings, we sought to examine the relation between BCL11B and arterial function. METHODS AND RESULTS: Here we report that BCL11B is expressed in the vascular smooth muscle where it regulates vascular stiffness. RNA sequencing of aortas from wild-type and Bcl11b null mice (BSMKO) identified the cGMP (cyclic guanosine monophosphate)-cGMP-dependent protein kinase G (PKG) as the most significant differentially regulated signaling pathway in BSMKO compared with wild-type mice. BSMKO aortas showed decreased levels of PKG1, increased levels of Ca++-calmodulin-dependent serine/threonine phosphatase calcineurin (PP2B) and decreased levels of their common phosphorylation target, phosphorylated vasodilator-stimulated phosphoprotein (pVASPS239), a regulator of cytoskelatal actin rearrangements. Decreased pVASPS239 in BSMKO aortas was associated with increased actin polymerization (filamentous/globular actin ratio). Functionally, aortic force, stress, wall tension, and stiffness, measured ex vivo in organ baths, were increased in BSMKO aortas, and BSMKO mice had increased pulse wave velocity, the in vivo index of arterial stiffness. Despite having no effect on blood pressure or microalbuminuria, increased arterial stiffness in BSMKO mice was associated with increased incidence of cerebral microbleeds compared with age-matched wild-type littermates. CONCLUSIONS: We have identified vascular smooth muscle BCL11B as a crucial regulator of aortic smooth muscle function and a potential therapeutic target for vascular stiffness.R01 HL136311 - NHLBI NIH HHS; R01 AG053274 - NIA NIH HHS; R01 HL107385 - NHLBI NIH HHS; T32 HL007224 - NHLBI NIH HHS; P30 DK046200 - NIDDK NIH HHS; R01 HL105287 - NHLBI NIH HHS; R01 HL070100 - NHLBI NIH HHS; R01 HL126136 - NHLBI NIH HHS; R21 AG050599 - NIA NIH HHS; R01 HL080124 - NHLBI NIH HHS; R01 AI067846 - NIAID NIH HHSPublished versio

Growth of Long Range Forward-Backward Multiplicity Correlations with Centrality in Au+Au Collisions at sNN\sqrt{s_{NN}} = 200 GeV

Forward-backward multiplicity correlation strengths have been measured with the STAR detector for Au+Au and $\textit{p+p}$ collisions at $\sqrt{s_{NN}}$ = 200 GeV. Strong short and long range correlations (LRC) are seen in central Au+Au collisions. The magnitude of these correlations decrease with decreasing centrality until only short range correlations are observed in peripheral Au+Au collisions. Both the Dual Parton Model (DPM) and the Color Glass Condensate (CGC) predict the existence of the long range correlations. In the DPM the fluctuation in the number of elementary (parton) inelastic collisions produces the LRC. In the CGC longitudinal color flux tubes generate the LRC. The data is in qualitative agreement with the predictions from the DPM and indicates the presence of multiple parton interactions.Comment: 6 pages, 3 figures The abstract has been slightly modifie

Finite element simulation of nonlinear convective heat and mass transfer in a micropolar fluid-filled enclosure with Rayleigh number effects

A mathematical model is presented to study the double-diffusive convective heat and mass transfer of a micropolar biofluid in a rectangular enclosure, as a model of transport phenomena in a bioreactor. The vertical walls of the enclosure are maintained at constant but different temperatures and concentrations. The conservation equations for linear momentum, angular momentum, energy and species concentration are formulated subject to appropriate boundary conditions and solved using both finite element and finite difference numerical techniques. Results are shown to be in excellent agreement between these methods. Several special cases of the flow regime are discussed. The distributions for streamline, isotemperature, isoconcentration and (isomicrorotation) are presented graphically for different Lewis number, buoyancy parameter, micropolar vortex viscosity parameter, gyration viscosity parameter, Rayleigh number, Prandtl number and micro-inertia parameter. Micropolar material parameters are shown to considerably influence the flow regime. The flow model has important applications in hybrid aerobic bioreactor systems exploiting rheological suspensions e.g. fermentation

Earth: Atmospheric Evolution of a Habitable Planet

Our present-day atmosphere is often used as an analog for potentially habitable exoplanets, but Earth's atmosphere has changed dramatically throughout its 4.5 billion year history. For example, molecular oxygen is abundant in the atmosphere today but was absent on the early Earth. Meanwhile, the physical and chemical evolution of Earth's atmosphere has also resulted in major swings in surface temperature, at times resulting in extreme glaciation or warm greenhouse climates. Despite this dynamic and occasionally dramatic history, the Earth has been persistently habitable--and, in fact, inhabited--for roughly 4 billion years. Understanding Earth's momentous changes and its enduring habitability is essential as a guide to the diversity of habitable planetary environments that may exist beyond our solar system and for ultimately recognizing spectroscopic fingerprints of life elsewhere in the Universe. Here, we review long-term trends in the composition of Earth's atmosphere as it relates to both planetary habitability and inhabitation. We focus on gases that may serve as habitability markers (CO2, N2) or biosignatures (CH4, O2), especially as related to the redox evolution of the atmosphere and the coupled evolution of Earth's climate system. We emphasize that in the search for Earth-like planets we must be mindful that the example provided by the modern atmosphere merely represents a single snapshot of Earth's long-term evolution. In exploring the many former states of our own planet, we emphasize Earth's atmospheric evolution during the Archean, Proterozoic, and Phanerozoic eons, but we conclude with a brief discussion of potential atmospheric trajectories into the distant future, many millions to billions of years from now. All of these 'Alternative Earth' scenarios provide insight to the potential diversity of Earth-like, habitable, and inhabited worlds.Comment: 34 pages, 4 figures, 4 tables. Review chapter to appear in Handbook of Exoplanet

System size dependence of associated yields in hadron-triggered jets

We present results on the system size dependence of high transverse momentum di-hadron correlations at $\sqrt{s_{NN}}$ = 200 GeV as measured by STAR at RHIC. Measurements in d+Au, Cu+Cu and Au+Au collisions reveal similar jet-like correlation yields at small angular separation ($\Delta\phi\sim0$, $\Delta\eta\sim0$) for all systems and centralities. Previous measurements have shown that the away-side yield is suppressed in heavy-ion collisions. We present measurements of the away-side suppression as a function of transverse momentum and centrality in Cu+Cu and Au+Au collisions. The suppression is found to be similar in Cu+Cu and Au+Au collisions at a similar number of participants. The results are compared to theoretical calculations based on the parton quenching model and the modified fragmentation model. The observed differences between data and theory indicate that the correlated yields presented here will provide important constraints on medium density profile and energy loss model parameters.Comment: 12 pages, 5 figure

Unsupervised compositionality prediction of nominal compounds

Nominal compounds such as red wine and nut case display a continuum of compositionality, with varying contributions from the components of the compound to its semantics. This article proposes a framework for compound compositionality prediction using distributional semantic models, evaluating to what extent they capture idiomaticity compared to human judgments. For evaluation, we introduce data sets containing human judgments in three languages: English, French, and Portuguese. The results obtained reveal a high agreement between the models and human predictions, suggesting that they are able to incorporate information about idiomaticity. We also present an in-depth evaluation of various factors that can affect prediction, such as model and corpus parameters and compositionality operations. General crosslingual analyses reveal the impact of morphological variation and corpus size in the ability of the model to predict compositionality, and of a uniform combination of the components for best results

Beam-Energy and System-Size Dependence of Dynamical Net Charge Fluctuations

We present measurements of net charge fluctuations in $Au + Au$ collisions at $\sqrt{s_{NN}} =$ 19.6, 62.4, 130, and 200 GeV, $Cu + Cu$ collisions at $\sqrt{s_{NN}} =$ 62.4, 200 GeV, and $p + p$ collisions at $\sqrt{s} =$ 200 GeV using the dynamical net charge fluctuations measure $\nu_{+-{\rm,dyn}}$. We observe that the dynamical fluctuations are non-zero at all energies and exhibit a modest dependence on beam energy. A weak system size dependence is also observed. We examine the collision centrality dependence of the net charge fluctuations and find that dynamical net charge fluctuations violate $1/N_{ch}$ scaling, but display approximate $1/N_{part}$ scaling. We also study the azimuthal and rapidity dependence of the net charge correlation strength and observe strong dependence on the azimuthal angular range and pseudorapidity widths integrated to measure the correlation.Comment: 15 pages, 6 figures, STAR Collaboratio

Gamma Prime Precipitate Evolution During Aging of a Model Nickel-Based Superalloy

The microstructural stability of nickel-based superalloys is critical for maintaining alloy performance during service in gas turbine engines. In this study, the precipitate evolution in a model polycrystalline Ni-based superalloy during aging to 1000 hours has been studied via transmission electron microscopy, atom probe tomography and neutron diffraction. Variations in phase composition and precipitate morphology, size and volume fraction were observed during aging, whilst the constrained lattice misfit remained constant at approximately zero. The experimental composition of the γ matrix phase was consistent with thermodynamic equilibrium predictions, whilst significant differences were identified between the experimental and predicted results from the γʹ phase. These results have implications for the evolution of mechanical properties in service and their prediction using modeling methods.The authors wish to acknowledge Mrs. S. Rhodes, Dr. H.T. Pang, Dr. D.M. Collins, and Dr. O.M.D.M. Messé for their assistance with the experiments performed. Funding was provided by the EPSRC/Rolls-Royce Strategic Partnership under EP/M005607/1 and EP/H022309/1. The Oxford Atom Probe facility was funded by the EPSRC under EP/M022803/1. Neutron diffraction beam time was supported through the Canadian Neutron Beam Centre under Experiment number 1258

A Gaseous Argon-Based Near Detector to Enhance the Physics Capabilities of DUNE

This document presents the concept and physics case for a magnetized gaseous argon-based detector system (ND-GAr) for the Deep Underground Neutrino Experiment (DUNE) Near Detector. This detector system is required in order for DUNE to reach its full physics potential in the measurement of CP violation and in delivering precision measurements of oscillation parameters. In addition to its critical role in the long-baseline oscillation program, ND-GAr will extend the overall physics program of DUNE. The LBNF high-intensity proton beam will provide a large flux of neutrinos that is sampled by ND-GAr, enabling DUNE to discover new particles and search for new interactions and symmetries beyond those predicted in the Standard Model