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

Desempenho produtivo de ovinos mantidos em pastagens de capim Tifton 85 recebendo doses crescentes de concentrado.

O estudo foi conduzido com o objetivo de avaliar o desempenho produtivo de ovinos mantidos em pastagens irrigadas de Tifton 85 recebendo doses crescentes de suplemento concentrado. Foram utilizados 24 ovinos, machos, castrados, com peso médio inicial de 20 kg como animais testadores. As doses de concentrado avaliadas foram 0; 0,66; 1,33 e 2,0% de matéria seca de suplemento em relação ao peso corporal dos animais. O delineamento experimental foi o inteiramente casualizado com seis repetições por tratamento. Foram observados maiores (P<0,05) ganhos médios diários e ganhos de pesos totais para os animais que receberam 2% de concentrado. Os animais que não receberam suplementação apresentaram os menores (P<0,05) ganhos médios diários e ganhos de pesos totais. O aumento nas doses de concentrado para ovinos mantidos em pastagens de Tifton 85 melhorou o desempenho produtivo dos animais

Large scale structure and the generalised Chaplygin gas as dark energy

The growth of large scale structure is studied in a universe containing both cold dark matter (CDM) and generalized Chaplygin gas (GCg). GCg is assumed to contribute only to the background evolution of the universe while the CDM component collapses and forms structures. We present some new analytical as well as numerical results for linear and non-linear growth in such model. The model passes the standard cosmological distance test without the need of a cosmological constant (LCDM). But we find that the scenario is severely constrained by current observations of large scale structure. Any small deviations of the GCg parameters away from the standard Lambda dominated cosmology (LCDM) produces substantial suppression for the growth of structures.Comment: 6 pages, matches version accepted for publication in Phys.Rev.D (in press

PSNCBAM-1 analogs: Structural evolutions and allosteric properties at cannabinoid CB1 receptor

Allosteric modulation of the CB1Rs could represent an alternative strategy for the treatment of diseases in which these receptors are involved, without the undesirable effects associated with their orthosteric stimulation. PSNCBAM-1 is a reference diaryl urea derivative that positively affects the binding affinity of orthosteric ligands (PAM) and negatively affects the functional activity of orthosteric ligands (NAM) at CB1Rs. In this work we reported the design, synthesis and biological evaluation of three different series of compounds, derived from structural modifications of PSNCBAM-1 and its analogs reported in the recent literature. Almost all the new compounds increased the percentage of binding affinity of CP55940 at CB1Rs, showing a PAM profile. When tested alone in the [35S]GTPγS functional assay, only a few derivatives lacked detectable activity, so were tested in the same functional assay in the presence of CP55940. Among these, compounds 11 and 18 proved to be functional NAMs at CB1Rs, dampening the orthosteric agonist-induced receptor functionality by approximately 30%. The structural features presented in this work provide new CB1R-allosteric modulators (with a profile similar to the reference compound PSNCBAM-1) and an extension of the structure-activity relationships for this type of molecule at CB1Rs

Composição química da carne de cabritos Saanen arraçoados com diferentes proporções de concentrado e volumoso.

O objetivo do presente estudo foi avaliar a composição química da carne de cabritos da raça Saanen submetidos a quatro relações de concentrado e volumoso (C:V) (80:20; 60:40; 40:60 e 20:80% de C:V) na matéria seca de rações, tendo o capim Elefante in natura picado como volumoso base. Foram utilizados 28 caprinos, machos, distribuídos em quatro grupos, em baias coletivas, sendo que, cada baia continha sete animais. O delineamento experimental adotado foi o inteiramente casualizado com sete repetições por tratamento. As variáveis analisadas foram os teores de matéria seca, proteína bruta, extrato etéreo e cinzas. Foram observados maiores teores de matéria seca (P0,05) pelas doses de concentrado. Assim, o incremento na proporção de concentrado nas rações elevou os teores de matéria seca da carne caprina

Static Configurations of Dark Energy and Dark Matter

We study static configurations of dark matter coupled to a scalar field responsible for the dark energy of the Universe. The dark matter is modelled as a Fermi gas within the Thomas-Fermi approximation. The mass of the dark matter particles is a function of the scalar field. We analyze the profile of the dark matter halos in galaxies. In this case our framework is equivalent to the model of the isothermal sphere. In the presence of a scalar field, the velocity of a massive object orbiting the galaxy is not of the order of the typical velocity of the dark matter particles, as in the conventional picture. Instead, it is reduced by a factor that quantifies the dependence of the dark matter mass on the scalar field. This has implications for dark matter searches. We derive new solutions of the Einstein equations which describe compact objects composed of dark matter. Depending on the scale of the dark matter mass, the size of these objects can vary between microscopic scales and cosmological distances. We determine the mass to radius relation and discuss the similarities with conventional neutron stars and exotic astrophysical objects.Comment: 23 pages, 3 figures, minor additions to the tex

Cosmological Models and Latest Observational Data

In this note, we consider the observational constraints on some cosmological models by using the 307 Union type Ia supernovae (SNIa), the 32 calibrated Gamma-Ray Bursts (GRBs) at $z>1.4$, the updated shift parameter $R$ from WMAP 5-year data (WMAP5), and the distance parameter $A$ of the measurement of the baryon acoustic oscillation (BAO) peak in the distribution of SDSS luminous red galaxies with the updated scalar spectral index $n_s$ from WMAP5. The tighter constraints obtained here update the ones obtained previously in the literature.Comment: 10 pages, 5 figures, 1 table, revtex4; v2: discussions added, accepted by Eur. Phys. J. C; v3: published versio

20-ps resolution Clock Distribution Network for a fast-timing single photon detector

The time resolution of active pixel sensors whose timestamp mechanism is based on Time-to-Digital Converters is critically linked to the accuracy in the distribution of the master clock signal that latches the timestamp values across the detector. The Clock Distribution Network that delivers the master clock signal must compensate process-voltage-temperature variations to reduce static time errors (skew), and minimize the power supply bounce to prevent dynamic time errors (jitter). To achieve sub-100ps time resolution within pixel detectors and thus enable a step forward in multiple imaging applications, the network latencies must be adjusted in steps well below that value. Power consumption must be kept as low as possible. In this work, a self-regulated Clock Distribution Network that fulfills these requirements is presented for the FastICpix single photon detector ¿ aiming at a 65nm process. A 40 MHz master clock is distributed to 64x64 pixels over an area of 2.4x2.4 cm2 using digital Delay-Locked Loops, achieving clock leaf skew below 20 ps with a power consumption of 26 mW. Guidelines are provided to adapt the system to arbitrary chip area and pixel pitch values, yielding a versatile design with very fine time resolution

One simulation to fit them all - changing the background parameters of a cosmological N-body simulation

We demonstrate that the output of a cosmological N-body simulation can, to remarkable accuracy, be scaled to represent the growth of large-scale structure in a cosmology with parameters similar to but different from those originally assumed. Our algorithm involves three steps: a reassignment of length, mass and velocity units, a relabelling of the time axis, and a rescaling of the amplitudes of individual large-scale fluctuation modes. We test it using two matched pairs of simulations. Within each pair, one simulation assumes parameters consistent with analyses of the first-year WMAP data. The other has lower matter and baryon densities and a 15% lower fluctuation amplitude, consistent with analyses of the three-year WMAP data. The pairs differ by a factor of a thousand in mass resolution, enabling performance tests on both linear and nonlinear scales. Our scaling reproduces the mass power spectra of the target cosmology to better than 0.5% on large scales (k < 0.1 h/Mpc) both in real and in redshift space. In particular, the BAO features of the original cosmology are removed and are correctly replaced by those of the target cosmology. Errors are still below 3% for k < 1 h/Mpc. Power spectra of the dark halo distribution are even more precisely reproduced, with errors below 1% on all scales tested. A halo-by-halo comparison shows that centre-of-mass positions and velocities are reproduced to better than 90 kpc/h and 5%, respectively. Halo masses, concentrations and spins are also reproduced at about the 10% level, although with small biases. Halo assembly histories are accurately reproduced, leading to central galaxy magnitudes with errors of about 0.25 magnitudes and a bias of about 0.13 magnitudes for a representative semi-analytic model.Comment: 14 pages, 12 figures. Submitted to MNRA