Glucocorticoid Receptor Antagonist Mifepristone Does Not Alter Innate Anxiety-Like Behavior in Genetically-Selected Marchigian Sardinian (msP) Rats

Marchigian Sardinian alcohol-preferring (msP) rats serve as a unique model of heightened alcohol preference and anxiety disorders. Their innate enhanced stress and poor stress-coping strategies are driven by a genetic polymorphism of the corticotropin-releasing factor receptor 1 (CRF1) in brain areas involved in glucocorticoid signaling. The activation of glucocorticoid receptors (GRs) regulates the stress response, making GRs a candidate target to treat stress and anxiety. Here, we examined whether mifepristone, a GR antagonist known to reduce alcohol drinking in dependent rats, decreases innate symptoms of anxiety in msPs. Male and female msPs were compared to non-selected Wistar counterparts across three separate behavioral tests. We assessed anxiety-like behavior via the novelty-induced hypophagia (NIH) assay. Since sleep disturbances and hyperarousal are common features of stress-related disorders, we measured sleeping patterns using the comprehensive lab monitoring system (CLAMS) and stress sensitivity using acoustic startle measures. Rats received an acute administration of vehicle or mifepristone (60 mg/kg) 90 min prior to testing on NIH, acoustic startle response, and CLAMS. Our results revealed that both male and female msPs display greater anxiety-like behaviors as well as enhanced acoustic startle responses compared to Wistar counterparts. Male msPs also displayed reduced sleeping bout duration versus Wistars, and female msPs displayed greater acoustic startle responses versus male msPs. Importantly, the enhanced anxiety-like behavior and startle responses were not reduced by mifepristone. Together, these findings suggest that increased expression of stress-related behaviors in msPs are not solely mediated by acute activation of GRs.     

PlGF Immunological Impact during Pregnancy

During pregnancy, the mother’s immune system has to tolerate the persistence of paternal alloantigens without affecting the anti-infectious immune response. Consequently, several mechanisms aimed at preventing allograft rejection, occur during a pregnancy. In fact, the early stages of pregnancy are characterized by the correct balance between inflammation and immune tolerance, in which proinflammatory cytokines contribute to both the remodeling of tissues and to neo-angiogenesis, thus, favoring the correct embryo implantation. In addition to the creation of a microenvironment able to support both immunological privilege and angiogenesis, the trophoblast invades normal tissues by sharing the same behavior of invasive tumors. Next, the activation of an immunosuppressive phase, characterized by an increase in the number of regulatory T (Treg) cells prevents excessive inflammation and avoids fetal immuno-mediated rejection. When these changes do not occur or occur incompletely, early pregnancy failure follows. All these events are characterized by an increase in different growth factors and cytokines, among which one of the most important is the angiogenic growth factor, namely placental growth factor (PlGF). PlGF is initially isolated from the human placenta. It is upregulated during both pregnancy and inflammation. In this review, we summarize current knowledge on the immunomodulatory effects of PlGF during pregnancy, warranting that both innate and adaptive immune cells properly support the early events of implantation and placental development. Furthermore, we highlight how an alteration of the immune response, associated with PlGF imbalance, can induce a hypertensive state and lead to the pre-eclampsia (PE).     

Multitarget Compounds for Bipolar Disorder: From Rational Design to Preliminary Pharmacokinetic Evaluation

Due to the complex and multifactorial nature of bipolar disorder (BD), single-target drugs have traditionally provided limited relief with no disease-modifying effects. In line with the polypharmacology paradigm, we attempted to overcome these limitations by devising two series of multitarget-directed ligands endowed with both a partial agonist profile at dopamine receptor D3 (D3R) and inhibitory activity against glycogen synthase kinase 3 beta (GSK-3β). These are two structurally unrelated targets that play independent, yet connected, roles in cognition and mood regulation. Two compounds ( 7 and 10 ) emerged as promising D3R/GSK-3β multitarget-directed ligands with nanomolar activity at D3R and low-micromolar inhibition of GSK-3β, thereby confirming, albeit preliminarily, the feasibility of our strategy. Furthermore, 7 showed promising drug-like properties in stability and pharmacokinetic studies.     

Low frequency noise in 0.12 μm partially and fully depleted SOI technology

Low frequency noise characterization of 0.12 μm silicon-on-insulator (SOI) CMOS technology is for the first time performed for partially and fully depleted N-MOSFETs. Static performances of the experimental devices are first presented, then we address the drain current fluctuations in both linear and saturation regimes. Taking into consideration the usually admitted 1/f noise models in MOS devices and their applicability in our case, we point out an enhancement of the extracted trap densities for both architectures compared to previously obtained results in 0.25 μm SOI CMOS technology. As regards drain current spectral densities in saturation mode, we notice some peculiarities occurring for the Kink-related excess noise.     

Qualitative simulation of urea extraction during dialysis

The methodologies of qualitative reasoning are applied to the urea extraction process. The information obtained by quantitative simulation is compared with that acquired by qualitative analysis. It is found that qualitative simulation can specify the response of the dialysis system, as it is usually described in the literature, with no substantial variations. The possibility of using a qualitative approach to establish the characteristics of the system and to provide a general framework for more detailed quantitative analysis is investigated     

New experimental findings on hot carrier effects in sub-0.1 μmMOSFET's

The behaviors of the substrate current and the impact ionization rate are investigated for deep submicron devices in a wide temperature range. New important features are shown for the variations of the maximum substrate current as a function of applied biases and temperature. It is found that the gate voltage V_gmax, corresponding to the maximum impact ionization current conditions, is quasi-constant as a Function of the drain bias for sub-0.1 μm MOSFET's in the room temperature range. At low temperature, a substantial increase of V_gmax is observed when the drain voltage is reduced. It is also shown that, although a significant enhancement of hot carrier effects is observed by scaling down the devices, a strong reduction of the impact ionization rate is obtained for sub-0.1 μm MOSFET's operated at liquid nitrogen temperature in the low drain voltage range     

Elastic incoherent neutron scattering operating by varying instrumental energy resolution: principle, simulations, and experiments of the resolution elastic neutron scattering (RENS)

The main aim of this paper is to present the scientific case of the resolution elastic neutron scattering (RENS) method that is based on the collection of elastic neutron scattering intensity as a function of the instrumental energy resolution and that is able to extract information on the system dynamical properties from an elastic signal. In this framework, it is shown that in the measured elastic scattering law, as a function of the instrumental energy resolution, an inflection point occurs when the instrumental energy resolution intersects the system relaxation time, and in an equivalent way, a transition in the temperature behavior of the measured elastic scattering law occurs when the characteristic system relaxation time crosses the instrumental energy resolution time. With regard to the latter, an operative protocol to determine the system characteristic time by different elastic incoherent neutron scattering (EINS) thermal scans at different instrumental energy resolutions is also proposed. The proposed method, hence, is not primarily addressed to collect the measured elastic scattering intensity with a great accuracy, but rather relies on determining an inflection point in the measured elastic scattering law versus instrumental energy resolution. The RENS method is tested both numerically and experimentally. As far as numerical simulations are concerned, a simple model system for which the temperature behavior of the relaxation time follows an Arrhenius law, while its scattering law follows a Gaussian behavior, is considered. It is shown that the system relaxation time used as an input for the simulations coincides with the one obtained by the RENS approach. Regarding the experimental findings, due to the fact that a neutron scattering spectrometer working following the RENS method has not been constructed yet, different EINS experiments with different instrumental energy resolutions were carried out on a complex model system, i.e., dry and D(2)O hydrated lysozyme, in an extended temperature range. The resulting temperature behavior of the system relaxation time, obtained with RENS method, agrees very well with the one obtained in literature, for the same system, following the quasi-elastic neutron scattering (QENS) approach. The proposed scientific case puts into evidence the challenges of an RENS spectrometer working by varying the instrumental energy resolution; in particular, in comparison with QENS, the proposed RENS method requires a smaller amount of sample, which is an important point in dealing with biological and exotic systems; it is not affected by the use of model functions for fitting spectra as in QENS, but furnishes a direct access to relevant information.     

Whiteness Constraints in a Unified Variational Framework for Image Restoration

We propose a robust variational model for the restoration of images corrupted by blur and the general class of additive white noises. The key idea behind our proposal relies on a novel hard constraint imposed on the residual of the restoration, namely we characterize a residual whiteness set to which the restored image must belong. As the feasible set is unbounded, solution existence results for the proposed variational model are given. Moreover, based on theoretical derivations as well as on Monte Carlo simulations, we provide well-founded guidelines for setting the whiteness constraint limits. The solution of the non-trivial optimization problem, due to the non-smooth non-convex proposed model, is efficiently obtained by an alternating directions method of multipliers, which in particular reduces the solution to a sequence of convex optimization subproblems. Numerical results show the potentiality of the proposed model for restoring blurred images corrupted by several kinds of additive white noises.     

Viscous Taylor droplets in axisymmetric and planar tubes: from Bretherton’s theory to empirical models

The aim of this study is to derive accurate models for quantities characterizing the dynamics of droplets of non-vanishing viscosity in capillaries. In particular, we propose models for the uniform-film thickness separating the droplet from the tube walls, for the droplet front and rear curvatures and pressure jumps, and for the droplet velocity in a range of capillary numbers, Ca, from \(10^{-4}\) to 1 and inner-to-outer viscosity ratios, \(\lambda\), from 0, i.e. a bubble, to high-viscosity droplets. Theoretical asymptotic results obtained in the limit of small capillary number are combined with accurate numerical simulations at larger Ca. With these models at hand, we can compute the pressure drop induced by the droplet. The film thickness at low capillary numbers (\(Ca<10^{-3}\)) agrees well with Bretherton’s scaling for bubbles as long as \(\lambda <1\). For larger viscosity ratios, the film thickness increases monotonically, before saturating for \(\lambda>10^3\) to a value \(2^{2/3}\) times larger than the film thickness of a bubble. At larger capillary numbers, the film thickness follows the rational function proposed by Aussillous and Quéré (Phys Fluids 12(10):2367–2371, 2000) for bubbles, with a fitting coefficient which is viscosity-ratio dependent. This coefficient modifies the value to which the film thickness saturates at large capillary numbers. The velocity of the droplet is found to be strongly dependent on the capillary number and viscosity ratio. We also show that the normal viscous stresses at the front and rear caps of the droplets cannot be neglected when calculating the pressure drop for \(Ca>10^{-3}\).     

Surface Reconstruction,Oxidation Mechanism,and Stability of Cd3As2

Cadmium arsenide (Cd₃As₂) has recently attracted considerable interest for the presence of 3D massless Dirac fermions with ultrahigh mobility and magnetoresistance. However, its surface properties are currently largely unexplored both theoretically and experimentally, due to the very large unit cell and the challenging growth of single‐crystal samples, respectively. Here, by combining ab initio calculations with surface‐science spectroscopic experiments, the presence of a surface reconstruction is unveiled in centimeter‐scale (112)‐oriented Cd₃As₂ single‐crystal foils produced by the self‐selecting vapor growth. Outermost Cd atoms descend into the As‐sublayer with a subsequent self‐passivation of the dangling bonds with As atoms, forming the triangle lattice previously imaged by scanning tunneling microscopy. Moreover, the oxidation mechanism of this reconstructed surface, dominated by the formation of As? O? Cd bonds, is revealed. Interestingly, it is found that the band structure of the reconstructed surface of Cd₃As₂ is quite robust against surface oxidation. Both computational and experimental findings point to a successful exploitation in technology of Cd₃As₂ single crystals.