Development of an In Vivo RNAi Protocol to Investigate Gene Function in the Filarial Nematode, Brugia malayi

Our ability to control diseases caused by parasitic nematodes is constrained by a limited portfolio of effective drugs and a paucity of robust tools to investigate parasitic nematode biology. RNA interference (RNAi) is a reverse-genetics tool with great potential to identify novel drug targets and interrogate parasite gene function, but present RNAi protocols for parasitic nematodes, which remove the parasite from the host and execute RNAi in vitro, are unreliable and inconsistent. We have established an alternative in vivo RNAi protocol targeting the filarial nematode Brugia malayi as it develops in an intermediate host, the mosquito Aedes aegypti. Injection of worm-derived short interfering RNA (siRNA) and double stranded RNA (dsRNA) into parasitized mosquitoes elicits suppression of B. malayi target gene transcript abundance in a concentration-dependent fashion. The suppression of this gene, a cathepsin L-like cysteine protease (Bm-cpl-1) is specific and profound, both injection of siRNA and dsRNA reduce transcript abundance by 83%. In vivo Bm-cpl-1 suppression results in multiple aberrant phenotypes; worm motility is inhibited by up to 69% and parasites exhibit slow-moving, kinked and partial-paralysis postures. Bm-cpl-1 suppression also retards worm growth by 48%. Bm-cpl-1 suppression ultimately prevents parasite development within the mosquito and effectively abolishes transmission potential because parasites do not migrate to the head and proboscis. Finally, Bm-cpl-1 suppression decreases parasite burden and increases mosquito survival. This is the first demonstration of in vivo RNAi in animal parasitic nematodes and results indicate this protocol is more effective than existing in vitro RNAi methods. The potential of this new protocol to investigate parasitic nematode biology and to identify and validate novel anthelmintic drug targets is discussed

The expansion field: The value of H_0

Any calibration of the present value of the Hubble constant requires recession velocities and distances of galaxies. While the conversion of observed velocities into true recession velocities has only a small effect on the result, the derivation of unbiased distances which rest on a solid zero point and cover a useful range of about 4-30 Mpc is crucial. A list of 279 such galaxy distances within v<2000 km/s is given which are derived from the tip of the red-giant branch (TRGB), from Cepheids, and from supernovae of type Ia (SNe Ia). Their random errors are not more than 0.15 mag as shown by intercomparison. They trace a linear expansion field within narrow margins from v=250 to at least 2000 km/s. Additional 62 distant SNe Ia confirm the linearity to at least 20,000 km/s. The dispersion about the Hubble line is dominated by random peculiar velocities, amounting locally to <100 km/s but increasing outwards. Due to the linearity of the expansion field the Hubble constant H_0 can be found at any distance >4.5 Mpc. RR Lyr star-calibrated TRGB distances of 78 galaxies above this limit give H_0=63.0+/-1.6 at an effective distance of 6 Mpc. They compensate the effect of peculiar motions by their large number. Support for this result comes from 28 independently calibrated Cepheids that give H_0=63.4+/-1.7 at 15 Mpc. This agrees also with the large-scale value of H_0=61.2+/-0.5 from the distant, Cepheid-calibrated SNe Ia. A mean value of H_0=62.3+/-1.3 is adopted. Because the value depends on two independent zero points of the distance scale its systematic error is estimated to be 6%. Typical errors of H_0 come from the use of a universal, yet unjustified P-L relation of Cepheids, the neglect of selection bias in magnitude-limited samples, or they are inherent to the adopted models.Comment: 44 pages, 4 figures, 6 tables, accepted for publication in the Astronony and Astrophysics Review 15

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Search for flavor changing neutral currents in top quark decays in pp collisions at 7 TeV

The results of a search for flavor changing neutral currents in top quark decays t -> Zq in events with a topology compatible with the decay chain t (t) over bar -> Wb + Zq -> lvb + llq are presented. The search is performed with a data sample corresponding to an integrated luminosity of 5.0 fb(-1) of proton-proton collisions at a center-of-mass energy of 7 TeV, collected with the CMS detector at the LHC. The observed number of events agrees with the standard model prediction and no evidence for flavor changing neutral currents in top quark decays is found. A t -> Zq branching fraction greater than 0.21% is excluded at the 95% confidence level. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved

Search for supersymmetry in final states with missing transverse energy and 0, 1, 2, or >= 3 b-quark jets in 7 TeV pp collisions using the variable alpha(T)

A search for supersymmetry in final states with jets and missing transverse energy is performed in pp collisions at a centre-of-mass energy of root s = 7 TeV. The data sample corresponds to an integrated luminosity of 4.98 fb(-1) collected by the CMS experiment at the LHC. In this search, a dimensionless kinematic variable, alpha(T), is used as the main discriminator between events with genuine and misreconstructed missing transverse energy. The search is performed in a signal region that is binned in the scalar sum of the transverse energy of jets and the number of jets identified as originating from a bottom quark. No excess of events over the standard model expectation is found. Exclusion limits are set in the parameter space of the constrained minimal supersymmetric extension of the standard model, and also in simplified models, with a special emphasis on compressed spectra and third-generation scenarios

Measurement of the inelastic proton-proton cross section at root s=7 TeV

A measurement is presented of the inelastic proton-proton cross section at a centre-of-mass energy of root s = 7 TeV. Using the CMS detector at the LHC, the inelastic cross section is measured through two independent methods based on information from (i) forward calorimetry (for pseudorapidity 3 200 MeV/c. The measurements cover a large fraction of the inelastic cross section for particle production over about nine units of pseudorapidity and down to small transverse momenta. The results are compared with those of other experiments, and with models used to describe high-energy hadronic interactions. (C) 2013 CERN. Published by Elsevier B.V. All rights reserved

Search for long-lived particles in events with photons and missing energy in proton-proton collisions at root s=7 TeV

Results are presented from a search for long-lived neutralinos decaying into a photon and an invisible particle, a signature associated with gauge-mediated supersymmetry breaking in supersymmetric models. The analysis is based on a 4.9 fb(-1) sample of proton-proton collisions at root s = 7 TeV, collected with the CMS detector at the LHC. The missing transverse energy and the time of arrival of the photon at the electromagnetic calorimeter are used to search for an excess of events over the expected background. No significant excess is observed, and lower limits at the 95% confidence level are obtained on the mass of the lightest neutralino, m > 220 GeV (for c tau 6000 mm (for m < 150 GeV). (c) 2013 CERN. Published by Elsevier B.V. All rights reserved

Inclusive and differential measurements of the t(t)over-bar charge asymmetry in pp collisions at root s=8 TeV

The charge asymmetry is measured in proton–proton collisions at a centre-of-mass energy of . The data, collected with the CMS experiment at the LHC, correspond to an integrated luminosity of 19.7 fb−1. Selected events contain an electron or a muon and four or more jets, where at least one jet is identified as originating from b-quark hadronization. The inclusive charge asymmetry is found to be . In addition, differential charge asymmetries as a function of rapidity, transverse momentum, and invariant mass of the system are studied. For the first time at the LHC, the measurements are also performed in a reduced fiducial phase space of top quark pair production, with an integrated result of . All measurements are consistent within two standard deviations with zero asymmetry as well as with the predictions of the standard model