Anisotropic structure of homogeneous turbulence subjected to uniform rotation

Large-eddy simulation results are used to investigate the development of anisotropies and the possible transition towards a quasi two-dimensional state in rotating turbulence at high Reynolds number. The present study demonstrates the existence of two transitions that are identified by two Rossby numbers. The first transition marks the onset of anisotropic effects and corresponds to a macro Rossby number Ro(sup L) (based on a longitudinal integral length scale) near unity. A second transition can be defined in terms of a lower bound of micro-Rossby number Ro(sup w) also near unity (defined in this work as the ratio of the rms fluctuating vorticity to background vorticity) and corresponds to a continued development of anisotropy but with an increasing emergence of those indicators based on the pure two-dimensional component of the flow, e.g., integral length scales measured along the rotation axis. Investigation of the vorticity structure shows that the second transition is also characterized by an increasing tendency for alignment between the fluctuating vorticity vector and the basic angular velocity vector with a preference for corotative vorticity

Signatures of two-dimensionalisation of 3D turbulence in presence of rotation

A reason has been given for the inverse energy cascade in the two-dimensionalised rapidly rotating 3D incompressible turbulence. For such system, literature shows a possibility of the exponent of wavenumber in the energy spectrum's relation to lie between -2 and -3. We argue the existence of a more strict range of -2 to -7/3 for the exponent in the case of rapidly rotating turbulence which is in accordance with the recent experiments. Also, a rigorous derivation for the two point third order structure function has been provided helping one to argue that even with slow rotation one gets, though dominated, a spectrum with the exponent -2.87, thereby hinting at the initiation of the two-dimensionalisation effect with rotation.Comment: An extended and typos-corrected version of the earlier submissio

The decay of Batchelor and Saffman rotating turbulence

The decay rate of isotropic and homogeneous turbulence is known to be affected by the large-scale spectrum of the initial perturbations, associated with at least two cannonical self-preserving solutions of the von K\'arm\'an-Howarth equation: the so-called Batchelor and Saffman spectra. The effect of long-range correlations in the decay of anisotropic flows is less clear, and recently it has been proposed that the decay rate of rotating turbulence may be independent of the large-scale spectrum of the initial perturbations. We analyze numerical simulations of freely decaying rotating turbulence with initial energy spectra $\sim k^4$ (Batchelor turbulence) and $\sim k^2$ (Saffman turbulence) and show that, while a self-similar decay cannot be identified for the total energy, the decay is indeed affected by long-range correlations. The decay of two-dimensional and three-dimensional modes follows distinct power laws in each case, which are consistent with predictions derived from the anisotropic von K\'arm\'an-Howarth equation, and with conservation of anisotropic integral quantities by the flow evolution

Scaling and energy transfer in rotating turbulence

The inertial-range properties of quasi-stationary hydrodynamic turbulence under solid-body rotation are studied via high-resolution direct numerical simulations. For strong rotation the nonlinear energy cascade exhibits depletion and a pronounced anisotropy with the energy flux proceeding mainly perpendicularly to the rotation axis. This corresponds to a transition towards a quasi-two-dimensional flow similar to a linear Taylor-Proudman state. In contrast to the energy spectrum along the rotation axis which does not scale self-similarly, the perpendicular spectrum displays an inertial range with $k^{-2}_\perp$-behavior. A new phenomenology gives a rationale for the observations. The scaling exponents $\zeta_p$ of structure functions up to order $p=8$ measured perpendicular to the rotation axis indicate reduced intermittency with increasing rotation rate. The proposed phenomenology is consistent with the inferred asymptotic non-intermittent behavior $\zeta_p=p/2$.Comment: to be published in Europhysics Letters (www.epletters.net), minor changes to match version in prin

A scaling theory of 3D spinodal turbulence

A new scaling theory for spinodal decomposition in the inertial hydrodynamic regime is presented. The scaling involves three relevant length scales, the domain size, the Taylor microscale and the Kolmogorov dissipation scale. This allows for the presence of an inertial "energy cascade", familiar from theories of turbulence, and improves on earlier scaling treatments based on a single length: these, it is shown, cannot be reconciled with energy conservation. The new theory reconciles the t^{2/3} scaling of the domain size, predicted by simple scaling, with the physical expectation of a saturating Reynolds number at late times.Comment: 5 pages, no figures, revised version submitted to Phys Rev E Rapp Comm. Minor changes and clarification

On two-dimensionalization of three-dimensional turbulence in shell models

Applying a modified version of the Gledzer-Ohkitani-Yamada (GOY) shell model, the signatures of so-called two-dimensionalization effect of three-dimensional incompressible, homogeneous, isotropic fully developed unforced turbulence have been studied and reproduced. Within the framework of shell models we have obtained the following results: (i) progressive steepening of the energy spectrum with increased strength of the rotation, and, (ii) depletion in the energy flux of the forward forward cascade, sometimes leading to an inverse cascade. The presence of extended self-similarity and self-similar PDFs for longitudinal velocity differences are also presented for the rotating 3D turbulence case

AMPK activation protects from neuronal dysfunction and vulnerability across nematode, cellular and mouse models of Huntington's disease.

The adenosine monophosphate activated kinase protein (AMPK) is an evolutionary-conserved protein important for cell survival and organismal longevity through the modulation of energy homeostasis. Several studies suggested that AMPK activation may improve energy metabolism and protein clearance in the brains of patients with vascular injury or neurodegenerative disease. However, in Huntington's disease (HD), AMPK may be activated in the striatum of HD mice at a late, post-symptomatic phase of the disease, and high-dose regiments of the AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide may worsen neuropathological and behavioural phenotypes. Here, we revisited the role of AMPK in HD using models that recapitulate the early features of the disease, including Caenorhabditis elegans neuron dysfunction before cell death and mouse striatal cell vulnerability. Genetic and pharmacological manipulation of aak-2/AMPKα shows that AMPK activation protects C. elegans neurons from the dysfunction induced by human exon-1 huntingtin (Htt) expression, in a daf-16/forkhead box O-dependent manner. Similarly, AMPK activation using genetic manipulation and low-dose metformin treatment protects mouse striatal cells expressing full-length mutant Htt (mHtt), counteracting their vulnerability to stress, with reduction of soluble mHtt levels by metformin and compensation of cytotoxicity by AMPKα1. Furthermore, AMPK protection is active in the mouse brain as delivery of gain-of-function AMPK-γ1 to mouse striata slows down the neurodegenerative effects of mHtt. Collectively, these data highlight the importance of considering the dynamic of HD for assessing the therapeutic potential of stress-response targets in the disease. We postulate that AMPK activation is a compensatory response and valid approach for protecting dysfunctional and vulnerable neurons in HD

Preclinical Evaluation of a Lentiviral Vector for Huntingtin Silencing.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder resulting from a polyglutamine expansion in the huntingtin (HTT) protein. There is currently no cure for this disease, but recent studies suggest that RNAi to downregulate the expression of both normal and mutant HTT is a promising therapeutic approach. We previously developed a small hairpin RNA (shRNA), vectorized in an HIV-1-derived lentiviral vector (LV), that reduced pathology in an HD rodent model. Here, we modified this vector for preclinical development by using a tat-independent third-generation LV (pCCL) backbone and removing the original reporter genes. We demonstrate that this novel vector efficiently downregulated HTT expression in vitro in striatal neurons derived from induced pluripotent stem cells (iPSCs) of HD patients. It reduced two major pathological HD hallmarks while triggering a minimal inflammatory response, up to 6 weeks after injection, when administered by stereotaxic surgery in the striatum of an in vivo rodent HD model. Further assessment of this shRNA vector in vitro showed proper processing by the endogenous silencing machinery, and we analyzed gene expression changes to identify potential off-targets. These preclinical data suggest that this new shRNA vector fulfills primary biosafety and efficiency requirements for further development in the clinic as a cure for HD

Trials

BACKGROUND: An international workshop on population health intervention research (PHIR) was organized to foster exchanges between experts from different disciplines and different fields. AIMS: This paper aims to summarize the discussions around one of the issues addressed: the place or role of pilot studies in PHIR. Pilot studies are well-established in biomedical research, but the situation is more ambiguous for PHIR, in which a pilot study could refer to different purposes. METHODS: The workshop included formal presentations of participants and moderated discussions. An oral synthesis was carried out by a rapporteur to validate by expert consensus the key points of the discussion and the recommendations. All discussions have been recorded and fully transcribed. DISCUSSION: PHIR generally addresses complex interventions. Thus, numerous tasks may be required to inform the intervention and test different aspects of its design and implementation. While in clinical research the pilot study mainly concerns the preparation of the trial, in PHIR the pilot study focuses on the preparation of both the intervention and the trial. In particular, pilot studies in PHIR could be used for viability evaluation and theory development. RECOMMENDATIONS FROM THE WORKSHOP PARTICIPANTS: The following recommendations were generated by consensus from the workshop discussions: i) terms need to be clarified for PHIR; ii) reporting and publication should be standardized and transparency should be promoted; iii) the objectives and research questions should drive the methods used and be clearly stated; iv) a pilot study is generally needed for complex intervention evaluation and for research-designed programs; and v) for field-designed programs, it is important to integrate evaluability assessments as pilot studies . CONCLUSION: Pilot studies play an important role in intervention development and evaluation. In particular, they contribute to a better understanding of the mechanisms of intervention and the conditions of its applicability and transferability. Pilot studies could therefore facilitate evidence-based decisions about design and conduct of main studies aimed to generate evidence to inform public health policy