Large-scale Bias and Efficient Generation of Initial Conditions for Non-Local Primordial Non-Gaussianity

We study the scale-dependence of halo bias in generic (non-local) primordial non-Gaussian (PNG) initial conditions of the type motivated by inflation, parametrized by an arbitrary quadratic kernel. We first show how to generate non-local PNG initial conditions with minimal overhead compared to local PNG models for a general class of primordial bispectra that can be written as linear combinations of separable templates. We run cosmological simulations for the local, and non-local equilateral and orthogonal models and present results on the scale-dependence of halo bias. We also derive a general formula for the Fourier-space bias using the peak-background split (PBS) in the context of the excursion set approach to halos and discuss the difference and similarities with the known corresponding result from local bias models. Our PBS bias formula generalizes previous results in the literature to include non-Markovian effects and non-universality of the mass function and are in better agreement with measurements in numerical simulations than previous results for a variety of halo masses, redshifts and halo definitions. We also derive for the first time quadratic bias results for arbitrary non-local PNG, and show that non-linear bias loops give small corrections at large-scales. The resulting well-behaved perturbation theory paves the way to constrain non-local PNG from measurements of the power spectrum and bispectrum in galaxy redshift surveys.Comment: 43 pages, 10 figures. v2: references added. 2LPT parallel code for generating non-local PNG initial conditions available at http://cosmo.nyu.edu/roman/2LP

Medicinal Chemistry approach, pharmacology and neuroprotective benefits of CB2R modulators in neurodegenerative diseases

In the last decades, cannabinoid receptor 2 (CB2R) has continued to receive attention as a key therapeutic target in neuroprotection. Indeed, several findings highlight the neuroprotective effects of CB2R through suppression of both neuronal excitability and reactive microglia. Additionally, CB2R seems to be a more promising target than cannabinoid receptor 1 (CB1R) thanks to the lack of central side effects, its lower expression levels in the central nervous system (CNS), and its inducibility, since its expression enhances quickly in the brain following pathological conditions. This review aims to provide a thorough overview of the main natural and synthetic selective CB2R modulators, their chemical classification and their potential therapeutic usefulness in neuroprotection, a crucial aspect for the treatment of neurodegenerative diseases

The clustering of the SDSS main galaxy sample - II. Mock galaxy catalogues and a measurement of the growth of structure from redshift space distortions at z=0.15

Citation: Howlett, C., Ross, A. J., Samushia, L., Percival, W. J., & Manera, M. (2015). The clustering of the SDSS main galaxy sample - II. Mock galaxy catalogues and a measurement of the growth of structure from redshift space distortions at z=0.15. Monthly Notices of the Royal Astronomical Society, 449(1), 848-866. doi:10.1093/mnras/stu2693We measure redshift space distortions in the two-point correlation function of a sample of 63 163 spectroscopically identified galaxies with z < 0.2, an epoch where there are currently only limited measurements, from the Sloan Digital Sky Survey Data Release 7 main galaxy sample (MGS). Our sample, which we denote MGS, covers 6813 deg(2) with an effective redshift z(eff) = 0.15 and is described in our companion paper (Paper I), which concentrates on baryon acoustic oscillation (BAO) measurements. In order to validate the fitting methods used in both papers, and derive errors, we create and analyse 1000 mock catalogues using a new algorithm called PICOLA to generate accurate dark matter fields. Haloes are then selected using a friends-of-friends algorithm, and populated with galaxies using a halo-occupation distribution fitted to the data. Using errors derived from these mocks, we fit a model to the monopole and quadrupole moments of the MGS correlation function. If we assume no Alcock-Paczynski (AP) effect (valid at z = 0.15 for any smooth model of the expansion history), we measure the amplitude of the velocity field, f sigma(8), at z = 0.15 to be 0.49(-0.14)(+0.15) . We also measure f sigma(8) including the AP effect. This latter measurement can be freely combined with recent cosmic microwave background results to constrain the growth index of fluctuations, gamma Assuming a background Lambda cold dark matter cosmology and combining with current BAO data, we find gamma = 0.64 +/- 0.09, which is consistent with the prediction of general relativity (gamma approximate to 0.55), though with a slight preference for higher gamma and hence models with weaker gravitational interactions

On virialization with dark energy

We review the inclusion of dark energy into the formalism of spherical collapse, and the virialization of a two-component system, made of matter and dark energy. We compare two approaches in previous studies. The first assumes that only the matter component virializes, e.g. as in the case of a classic cosmological constant. The second approach allows the full system to virialize as a whole. We show that the two approaches give fundamentally different results for the final state of the system. This might be a signature discriminating between the classic cosmological constant which cannot virialize and a dynamical dark energy mimicking a cosmological constant. This signature is independent of the measured value of the equation of state. An additional issue which we address is energy non-conservation of the system, which originates from the homogeneity assumption for the dark energy. We propose a way to take this energy loss into account.Comment: 15 pages, 5 figures. Accepted for publication in JCA

Allosteric modulators targeting cannabinoid cb1 and cb2 receptors: Implications for drug discovery

Allosteric modulators of cannabinoid receptors hold great therapeutic potential, as they do not possess intrinsic efficacy, but instead enhance or diminish the receptor's response of orthosteric ligands allowing for the tempering of cannabinoid receptor signaling without the desensitization, tolerance and dependence. Allosteric modulators of cannabinoid receptors have numerous advantages over the orthosteric ligands such as higher receptor type selectivity, probe dependence and biased signaling, so they have a great potential to separate the therapeutic benefits from side effects own of orthosteric ligands. This review aims to give an overview of the CB1 and CB2 receptor allosteric modulators highlighting the structure-activity relationship and pharmacological profile of each classes, and their future promise

Increased functional coupling of the left amygdala and medial prefrontal cortex during the perception of communicative point-light stimuli

Interpersonal predictive coding (IPPC) describes the behavioral phenomenon whereby seeing a communicative rather than an individual action helps to discern a masked second agent. As little is known, yet, about the neural correlates of IPPC, we conducted a functional magnetic resonance imaging study in a group of 27 healthy participants using point-light displays of moving agents embedded in distractors. We discovered that seeing communicative compared to individual actions was associated with higher activation of right superior frontal gyrus, whereas the reversed contrast elicited increased neural activation in an action observation network that was activated during all trials. Our findings, therefore, potentially indicate the formation of action predictions and a reduced demand for executive control in response to communicative actions. Further, in a regression analysis, we revealed that increased perceptual sensitivity was associated with a deactivation of the left amygdala during the perceptual task. A consecutive psychophysiological interaction analysis showed increased connectivity of the amygdala with medial prefrontal cortex in the context of communicative compared to individual actions. Thus, whereas increased amygdala signaling might interfere with task-relevant processes, increased co-activation of the amygdala and the medial prefrontal cortex in a communicative context might represent the integration of mentalizing computations

A Consistent Comparison of Bias Models using Observational Data

We investigate five different models for the dark matter halo bias, ie., the ratio of the fluctuations of mass tracers to those of the underlying mass, by comparing their cosmological evolution using optical QSO and galaxy bias data at different redshifts, consistently scaled to the WMAP7 cosmology. Under the assumption that each halo hosts one extragalactic mass tracer, we use a $\chi^2$ minimization procedure to determine the free parameters of the bias models as well as to statistically quantify their ability to represent the observational data. Using the Akaike information criterion we find that the model that represents best the observational data is the Basilakos & Plionis (2001; 2003) model with the tracer merger extension of Basilakos, Plionis & Ragone-Figueroa (2008) model. The only other statistically equivalent model, as indicated by the same criterion, is the Tinker et al. (2010) model. Finally, we find an average, over the different models, dark matter halo mass that hosts optical QSOs of: $M_h\simeq 2.7 (\pm 0.6) \times 10^{12} h^{-1} M_{\odot}$, while the corresponding value for optical galaxies is: $M_h\simeq 6.3 (\pm 2.1) \times 10^{11} h^{-1} M_{\odot}$.Comment: MNRAS in press, 12 pages, 6 color figures, 4 table

Perfluorooctanoic acid exposure assessment on common carp liver through image and ultrastructural investigation

Perfluorooctanoic acid (PFOA) poses particular concern as an emerging pollutant in both surface and ground waters. Fish, as a natural inhabitant of these waters and being highly representative of vertebrates, represents an ideal animal model to assess the toxic effects of PFOA. Hereby, liver microscopic texture was comparatively evaluated in individuals of common carp subchronically exposed to PFOA using grayscale differential box counting, a fractal analysis method. Furthermore, liver cytoplasmic glycogen areas and ultrastructure were also evaluated and compared to the image analysis findings. Redundancy Analysis was performed to assess, in summary, how much the variation of fractal dimension and lacunarity was explained by the concentration of PFOA in liver, the mass of liver and the number of proliferating cell nuclear antigen (PCNA)-immunoreactive nuclei. Treatment group ordination was better determined by fractal dimension than lacunarity. Interestingly, a significant complexity increase was associated with the modification of liver microscopic texture due to PFOA exposure. This complexity increase was related to “cloudy swelling”, possibly representing a primarily adaptive strategy against PFOA challenge, rather than a slight, reversible form of degeneration as traditionally proposed. The occurrence of endoplasmic reticulum stress, unfolded protein reaction and hormetic response was proposed and discussed

Survey on the management of Pompe disease in routine clinical practice in Spain

Antibodies; Diagnosis; Pompe diseaseAnticuerpos; Diagnóstico; Enfermedad de pompeAnticossos; Diagnòstic; Malaltia de pompeBackground Despite the availability of several clinical guidelines, not all health professionals use their recommendations to manage patients with Pompe disease, a rare genetic disorder involving high-impact therapy. Through several discussion meetings and a survey, the present study aimed to learn about the management of Pompe disease in routine clinical practice in Spain, to improve clinical care in a real-life situation. Results The survey was sent to 42 healthcare professionals who manage patients with Pompe disease in their clinical practice. Although most respondents followed the clinical guidelines, clinical practice differed from the expert recommendations in many cases. Approximately 7% did not request a genetic study to confirm the diagnosis before starting treatment, and 21% considered that only two dried blood spot determinations suffice to establish the diagnosis. About 76% requested anti-GAA antibodies when there is a suspicion of lack of treatment efficacy, though a significant percentage of respondents have never requested such antibodies. According to 31% of the respondents, significant impairment of motor function and/or respiratory insufficiency is a requirement for authorizing medication at their hospital. Up to 26% waited for improvements over the clinical follow-up to maintain treatment and withdrew it in the absence of improvement since they did not consider disease stabilization to be a satisfactory outcome. Conclusions The results highlight the lack of experience and/or knowledge of some professionals caring for patients with Pompe disease. It is necessary to develop and disseminate simple guidelines that help to apply the expert recommendations better or centralize patient follow-up in highly specialized centers.Sanofi has sponsored this project without participating in the article’s design, data analysis, or writing