The aerodynamic design of an advanced rotor airfoil

An advanced rotor airfoil, designed utilizing supercritical airfoil technology and advanced design and analysis methodology is described. The airfoil was designed subject to stringent aerodynamic design criteria for improving the performance over the entire rotor operating regime. The design criteria are discussed. The design was accomplished using a physical plane, viscous, transonic inverse design procedure, and a constrained function minimization technique for optimizing the airfoil leading edge shape. The aerodynamic performance objectives of the airfoil are discussed

Martian meso/micro-scale winds and surface energy budget

Regional, diurnal and seasonal variations of surface temperature are particularly large on Mars. This is mostly due to the Martian surface remaining close to radiative equilibrium. Contrary to most terrestrial locations, contributions of sensible heat flux (i.e. conduction/convection exchanges between atmosphere and surface) to the surface energy budget [hereinafter SEB] are negligible on Mars owing to lowatmospheric density and heat capacity (e.g. Figure 2 in Savijärvi and Kauhanen, 2008). This radiative control of surface temperature is a key characteristic of the Martian environment and has crucial consequences on the the Martian geology, meteorology, exobiology, etc. In order to identify the impact of this Martian peculiarity to near-surface regional-to-local atmospheric circulations, we employ our recently-built Martian limited-area meteorological model (Spiga and Forget, 2009). We use horizontal resolutions adapted to the dynamical phenomena we aim to resolve: from several tens of kilometers to compute regional winds (mesoscale simulations) to several tens of meters to compute atmospheric boundary-layer winds (microscale or turbulent-resolving simulations, also called Large-Eddy Simulations, LES)

Aquaporin-4–binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2

Neuromyelitis optica (NMO)-immunoglobulin G (IgG) is a clinically validated serum biomarker that distinguishes relapsing central nervous system (CNS) inflammatory demyelinating disorders related to NMO from multiple sclerosis. This autoantibody targets astrocytic aquaporin-4 (AQP4) water channels. Clinical, radiological, and immunopathological data suggest that NMO-IgG might be pathogenic. Characteristic CNS lesions exhibit selective depletion of AQP4, with and without associated myelin loss; focal vasculocentric deposits of IgG, IgM, and complement; prominent edema; and inflammation. The effect of NMO-IgG on astrocytes has not been studied. In this study, we demonstrate that exposure to NMO patient serum and active complement compromises the membrane integrity of CNS-derived astrocytes. Without complement, astrocytic membranes remain intact, but AQP4 is endocytosed with concomitant loss of Na+-dependent glutamate transport and loss of the excitatory amino acid transporter 2 (EAAT2) . Our data suggest that EAAT2 and AQP4 exist in astrocytic membranes as a macromolecular complex. Transport-competent EAAT2 protein is up-regulated in differentiating astrocyte progenitors and in nonneural cells expressing AQP4 transgenically. Marked reduction of EAAT2 in AQP4-deficient regions of NMO patient spinal cord lesions supports our immunocytochemical and immunoprecipitation data. Thus, binding of NMO-IgG to astrocytic AQP4 initiates several potentially neuropathogenic mechanisms: complement activation, AQP4 and EAAT2 down-regulation, and disruption of glutamate homeostasis

Titin mutations in iPS cells define sarcomere insufficiency as a cause of dilated cardiomyopathy

Human mutations that truncate the massive sarcomere protein titin [TTN-truncating variants (TTNtvs)] are the most common genetic cause for dilated cardiomyopathy (DCM), a major cause of heart failure and premature death. Here we show that cardiac microtissues engineered from human induced pluripotent stem (iPS) cells are a powerful system for evaluating the pathogenicity of titin gene variants. We found that certain missense mutations, like TTNtvs, diminish contractile performance and are pathogenic. By combining functional analyses with RNA sequencing, we explain why truncations in the A-band domain of TTN cause DCM, whereas truncations in the I band are better tolerated. Finally, we demonstrate that mutant titin protein in iPS cell-derived cardiomyocytes results in sarcomere insufficiency, impaired responses to mechanical and {beta}-adrenergic stress, and attenuated growth factor and cell signaling activation. Our findings indicate that titin mutations cause DCM by disrupting critical linkages between sarcomerogenesis and adaptive remodeling

RNA signatures allow rapid identification of pathogens and antibiotic susceptibilities

With rising rates of drug-resistant infections, there is a need for diagnostic methods that rapidly can detect the presence of pathogens and reveal their susceptibility to antibiotics. Here we propose an approach to diagnosing the presence and drug-susceptibility of infectious diseases based on direct detection of RNA from clinical samples. We demonstrate that species-specific RNA signatures can be used to identify a broad spectrum of infectious agents, including bacteria, viruses, yeast, and parasites. Moreover, we show that the behavior of a small set of bacterial transcripts after a brief antibiotic pulse can rapidly differentiate drug-susceptible and -resistant organisms and that these measurements can be made directly from clinical materials. Thus, transcriptional signatures could form the basis of a uniform diagnostic platform applicable across a broad range of infectious agents

Branching Fractions of tau Leptons to Three Charged Hadrons

From electron-positron collision data collected with the CLEO detector operating at CESR near \sqrt{s}=10.6 GeV, improved measurements of the branching fractions for tau decays into three explicitly identified hadrons and a neutrino are presented as {\cal B}(\tau^-\to\pi^-\pi^+\pi^-\nu_\tau)=(9.13\pm0.05\pm0.46)%, {\cal B}(\tau^-\to K^-\pi^+\pi^-\nu_\tau)=(3.84\pm0.14\pm0.38)\times10^{-3}, {\cal B}(\tau^-\to K^-K^+\pi^-\nu_\tau)=(1.55\pm0.06\pm0.09)\times10^{-3}, and {\cal B}(\tau^-\to K^-K^+K^-\nu_\tau)<3.7\times10^{-5} at 90% C.L., where the uncertainties are statistical and systematic, respectively.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, to appear in Phys. Rev. Let

Study of the q^2-Dependence of B --> pi ell nu and B --> rho(omega)ell nu Decay and Extraction of |V_ub|

We report on determinations of |Vub| resulting from studies of the branching fraction and q^2 distributions in exclusive semileptonic B decays that proceed via the b->u transition. Our data set consists of the 9.7x10^6 BBbar meson pairs collected at the Y(4S) resonance with the CLEO II detector. We measure B(B0 -> pi- l+ nu) = (1.33 +- 0.18 +- 0.11 +- 0.01 +- 0.07)x10^{-4} and B(B0 -> rho- l+ nu) = (2.17 +- 0.34 +0.47/-0.54 +- 0.41 +- 0.01)x10^{-4}, where the errors are statistical, experimental systematic, systematic due to residual form-factor uncertainties in the signal, and systematic due to residual form-factor uncertainties in the cross-feed modes, respectively. We also find B(B+ -> eta l+ nu) = (0.84 +- 0.31 +- 0.16 +- 0.09)x10^{-4}, consistent with what is expected from the B -> pi l nu mode and quark model symmetries. We extract |Vub| using Light-Cone Sum Rules (LCSR) for 0<= q^2<16 GeV^2 and Lattice QCD (LQCD) for 16 GeV^2 <= q^2 < q^2_max. Combining both intervals yields |Vub| = (3.24 +- 0.22 +- 0.13 +0.55/-0.39 +- 0.09)x10^{-3}$ for pi l nu, and |Vub| = (3.00 +- 0.21 +0.29/-0.35 +0.49/-0.38 +-0.28)x10^{-3} for rho l nu, where the errors are statistical, experimental systematic, theoretical, and signal form-factor shape, respectively. Our combined value from both decay modes is |Vub| = (3.17 +- 0.17 +0.16/-0.17 +0.53/-0.39 +-0.03)x10^{-3}.Comment: 45 pages postscript, also available through http://w4.lns.cornell.edu/public/CLNS, submitted to PR

Sarcomere function activates a p53-dependent DNA damage response that promotes polyploidization and limits in vivo cell engraftment.

Human cardiac regeneration is limited by low cardiomyocyte replicative rates and progressive polyploidization by unclear mechanisms. To study this process, we engineer a human cardiomyocyte model to track replication and polyploidization using fluorescently tagged cyclin B1 and cardiac troponin T. Using time-lapse imaging, in vitro cardiomyocyte replication patterns recapitulate the progressive mononuclear polyploidization and replicative arrest observed in vivo. Single-cell transcriptomics and chromatin state analyses reveal that polyploidization is preceded by sarcomere assembly, enhanced oxidative metabolism, a DNA damage response, and p53 activation. CRISPR knockout screening reveals p53 as a driver of cell-cycle arrest and polyploidization. Inhibiting sarcomere function, or scavenging ROS, inhibits cell-cycle arrest and polyploidization. Finally, we show that cardiomyocyte engraftment in infarcted rat hearts is enhanced 4-fold by the increased proliferation of troponin-knockout cardiomyocytes. Thus, the sarcomere inhibits cell division through a DNA damage response that can be targeted to improve cardiomyocyte replacement strategies

Rate Measurement of D0→K+π−π0D^{0}\to K^{+}\pi^{-}\pi^{0} and Constraints on D0−D0‾D^{0} - \overline{D^{0}} Mixing

We present an observation and rate measurement of the decay D0 -> K+pi-pi0 produced in 9/fb of e+e- collisions near the Upsilon(4S) resonance. The signal is inconsistent with an upward fluctuation of the background by 4.9 standard deviations. We measured the rate of D0 -> K+pi-pi0 normalized to the rate of D0bar -> K+pi-pi0 to be 0.0043 +0.0011 -0.0010 (stat) +/- 0.0007 (syst). This decay can be produced by doubly-Cabibbo-suppressed decays or by the D0 evolving into a D0bar through mixing, followed by a Cabibbo-favored decay to K+pi-pi0. We also found the CP asymmetry A=(8 +25 -22)% to be consistent with zero.Comment: 10 pages postscript, also available through http://w4.lns.cornell.edu/public/CLN