Signatures of Primordial Non-Gaussianity in the Large-Scale Structure of the Universe

We discuss how primordial (e.g. inflationary) non-Gaussianity in the cosmological perturbations is left imprinted in the Large-Scale Structure of the universe. Our findings show that the information on the primordial non-Gaussianity set on super-Hubble scales flows into Post-Newtonian terms, leaving an observable imprint in the Large-Scale Structure. Future high-precision measurements of the statistics of the dark matter density and peculiar velocity fields will allow to pin down the primordial non-Gaussianity, thus representing a tool complementary to studies of the Cosmic Microwave Background anisotropies.Comment: 8 pages, LaTeX file; Revised to match the final version accepted for publication on JCAP (some comments and one figure added

A New Gauge for Computing Effective Potentials in Spontaneously Broken Gauge Theories

A new class of renormalizable gauges is introduced that is particularly well suited to compute effective potentials in spontaneously broken gauge theories. It allows one to keep free gauge parameters when computing the effective potential from vacuum graphs or tadpoles without encountering mixed propagators of would-be-Goldstone bosons and longitudinal modes of the gauge field. As an illustrative example several quantities are computed within the Abelian Higgs model, which is renormalized at the two-loop level. The zero temperature effective potential in the new gauge is compared to that in $R_\xi$ gauge at the one-loop level and found to be not only easier to compute but also to have a more convenient analytical structure. To demonstrate renormalizability of the gauge for the non-Abelian case, the renormalization of an SU(2)-Higgs model with completely broken gauge group and of an SO(3)-Higgs model with an unbroken SO(2) subgroup is outlined and renormalization constants are given at the one-loop level.Comment: 24 pages, figures produced by LaTeX, plain LaTeX, THU-93/16. (Completely revised. Essential changes. New stuff added. To appear in Phys.Rev.D.

Intervening to improve health indicators among Australian farm families

The Sustainable Farm Families project (http://www.sustainablefarmfamilies.org.au/) was a 3-year demonstration and education project designed to influence farmer behavior with respect to family health and well-being among cropping and grazing farmers in Victoria, New South Wales, and South Australia, Australia. The project was conducted by the Western District Health Service, Hamilton, Australia, in partnership with farmers; Farm Management 500 (peer discussion group); the Victorian Farmers Federation; Royal Melbourne Institute of Technology; and Land Connect. During the 3 years of the project, 128 farmers&mdash;men (70) and women (58)&mdash;were enrolled. The project utilized a combination of small group workshops, individualized health action plans, and health education opportunities to encourage farm safety and health behavior changes and to elicit sustained improvements in the following health indicators: body mass index (BMI), total cholesterol, fasting blood glucose, and blood pressure. Mean changes in these health indicators were analyzed using repeated measures analysis of variance (ANOVA) and McNemar\u27s test compared the proportion of individuals with elevated indicators. Among participants with elevated values at baseline, the following average reductions were observed: BMI 0.44 kg/m2 (p = .0034), total cholesterol 48.7 mg/dl (p &lt; .0001), blood glucose 10.1 mg/dl (p = .0016), systolic blood pressure 12.5 mm Hg (p &lt; .0001), and diastolic blood pressure 5.0 mm Hg (p = .0007). The proportion of participants with elevated total cholesterol at baseline decreased after 24 months (p &lt; .001). Such findings suggest that proactive intervention by farmer associations, rural health services, and government agencies may be an effective vehicle for promoting voluntary farm safety and health behavior change while empowering farm families to achieve measurable reductions in important health risk factors. <br /

Perturbative nonequilibrium dynamics of phase transitions in an expanding universe

A complete set of Feynman rules is derived, which permits a perturbative description of the nonequilibrium dynamics of a symmetry-breaking phase transition in $\lambda\phi^4$ theory in an expanding universe. In contrast to a naive expansion in powers of the coupling constant, this approximation scheme provides for (a) a description of the nonequilibrium state in terms of its own finite-width quasiparticle excitations, thus correctly incorporating dissipative effects in low-order calculations, and (b) the emergence from a symmetric initial state of a final state exhibiting the properties of spontaneous symmetry breaking, while maintaining the constraint $\equiv 0$. Earlier work on dissipative perturbation theory and spontaneous symmetry breaking in Minkowski spacetime is reviewed. The central problem addressed is the construction of a perturbative approximation scheme which treats the initial symmetric state in terms of the field $\phi$, while the state that emerges at later times is treated in terms of a field $\zeta$, linearly related to $\phi^2$. The connection between early and late times involves an infinite sequence of composite propagators. Explicit one-loop calculations are given of the gap equations that determine quasiparticle masses and of the equation of motion for $$ and the renormalization of these equations is described. The perturbation series needed to describe the symmetric and broken-symmetry states are not equivalent, and this leads to ambiguities intrinsic to any perturbative approach. These ambiguities are discussed in detail and a systematic procedure for matching the two approximations is described.Comment: 22 pages, using RevTeX. 6 figures. Submitted to Physical Review

Analytic and Numerical Study of Preheating Dynamics

We analyze the phenomenon of preheating,i.e. explosive particle production due to parametric amplification of quantum fluctuations in the unbroken case, or spinodal instabilities in the broken phase, using the Minkowski space $O(N)$ vector model in the large $N$ limit to study the non-perturbative issues involved. We give analytic results for weak couplings and times short compared to the time at which the fluctuations become of the same order as the tree level,as well as numerical results including the full backreaction.In the case where the symmetry is unbroken, the analytic results agree spectacularly well with the numerical ones in their common domain of validity. In the broken symmetry case, slow roll initial conditions from the unstable minimum at the origin, give rise to a new and unexpected phenomenon: the dynamical relaxation of the vacuum energy.That is, particles are abundantly produced at the expense of the quantum vacuum energy while the zero mode comes back to almost its initial value.In both cases we obtain analytically and numerically the equation of state which turns to be written in terms of an effective polytropic index that interpolates between vacuum and radiation-like domination. We find that simplified analysis based on harmonic behavior of the zero mode, giving rise to a Mathieu equation forthe non-zero modes miss important physics. Furthermore, analysis that do not include the full backreaction do not conserve energy, resulting in unbound particle production. Our results do not support the recent claim of symmetry restoration by non-equilibrium fluctuations.Finally estimates of the reheating temperature are given,as well as a discussion of the inconsistency of a kinetic approach to thermalization when a non-perturbatively large number of particles is created.Comment: Latex file, 52 pages and 24 figures in .ps files. Minor changes. To appear in Physical Review D, 15 December 199

NEB mutations disrupt the super-relaxed state of myosin and remodel the muscle metabolic proteome in nemaline myopathy

Nemaline myopathy (NM) is one of the most common non-dystrophic genetic muscle disorders. NM is often associated with mutations in the NEB gene. Even though the exact NEB-NM pathophysiological mechanisms remain unclear, histological analyses of patients' muscle biopsies often reveal unexplained accumulation of glycogen and abnormally shaped mitochondria. Hence, the aim of the present study was to define the exact molecular and cellular cascade of events that would lead to potential changes in muscle energetics in NEB-NM. For that, we applied a wide range of biophysical and cell biology assays on skeletal muscle fibres from NM patients as well as untargeted proteomics analyses on isolated myofibres from a muscle-specific nebulin-deficient mouse model. Unexpectedly, we found that the myosin stabilizing conformational state, known as super-relaxed state, was significantly impaired, inducing an increase in the energy (ATP) consumption of resting muscle fibres from NEB-NM patients when compared with controls or with other forms of genetic/rare, acquired NM. This destabilization of the myosin super-relaxed state had dynamic consequences as we observed a remodeling of the metabolic proteome in muscle fibres from nebulin-deficient mice. Altogether, our findings explain some of the hitherto obscure hallmarks of NM, including the appearance of abnormal energy proteins and suggest potential beneficial effects of drugs targeting myosin activity/conformations for NEB-NM.Peer reviewe

Myosin ATPase inhibition fails to rescue the metabolically dysregulated proteome of nebulin-deficient muscle

Abstract: Nemaline myopathy (NM) is a genetic muscle disease, primarily caused by mutations in the NEB gene (NEB-NM) and with muscle myosin dysfunction as a major molecular pathogenic mechanism. Recently, we have observed that the myosin biochemical super-relaxed state was significantly impaired in NEB-NM, inducing an aberrant increase in ATP consumption and remodelling of the energy proteome in diseased muscle fibres. Because the small-molecule Mavacamten is known to promote the myosin super-relaxed state and reduce the ATP demand, we tested its potency in the context of NEB-NM. We first conducted in vitro experiments in isolated single myofibres from patients and found that Mavacamten successfully reversed the myosin ATP overconsumption. Following this, we assessed its short-term in vivo effects using the conditional nebulin knockout (cNeb KO) mouse model and subsequently performing global proteomics profiling in dissected soleus myofibres. After a 4 week treatment period, we observed a remodelling of a large number of proteins in both cNeb KO mice and their wild-type siblings. Nevertheless, these changes were not related to the energy proteome, indicating that short-term Mavacamten treatment is not sufficient to properly counterbalance the metabolically dysregulated proteome of cNeb KO mice. Taken together, our findings emphasize Mavacamten potency in vitro but challenge its short-term efficacy in vivo. (Figure presented.). Key points: No cure exists for nemaline myopathy, a type of genetic skeletal muscle disease mainly derived from mutations in genes encoding myofilament proteins. Applying Mavacamten, a small molecule directly targeting the myofilaments, to isolated membrane-permeabilized muscle fibres from human patients restored myosin energetic disturbances. Treating a mouse model of nemaline myopathy in vivo with Mavacamten for 4 weeks, remodelled the skeletal muscle fibre proteome without any noticeable effects on energetic proteins. Short-term Mavacamten treatment may not be sufficient to reverse the muscle phenotype in nemaline myopathy.Peer reviewe

Genome-wide Analyses Identify KIF5A as a Novel ALS Gene

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.Peer reviewe

Search for stop and higgsino production using diphoton Higgs boson decays

Results are presented of a search for a "natural" supersymmetry scenario with gauge mediated symmetry breaking. It is assumed that only the supersymmetric partners of the top-quark (stop) and the Higgs boson (higgsino) are accessible. Events are examined in which there are two photons forming a Higgs boson candidate, and at least two b-quark jets. In 19.7 inverse femtobarns of proton-proton collision data at sqrt(s) = 8 TeV, recorded in the CMS experiment, no evidence of a signal is found and lower limits at the 95% confidence level are set, excluding the stop mass below 360 to 410 GeV, depending on the higgsino mass