Resonant plasma excitation by single-cycle THz pulses

In this paper, an alternative perspective for the generation of millimetric high-gradient resonant plasma waves is discussed. This method is based on the plasma-wave excitation by energetic single-cycle THz pulses whose temporal length is comparable to the plasma wavelength. The excitation regime discussed in this paper is the quasi-nonlinear regime that can be achieved when the normalized vector potential of the driving THz pulse is on the order of unity. To investigate this regime and determine the strength of the excited electric elds, a Particle-In-Cell (PIC) code has been used. It has been found that by exploiting THz pulses with characteristics currently available in laboratory, longitudinal electron plasma waves with electric gradients up to hundreds MV/m can be obtained. The mm-size nature of the resonant plasma wave can be of great utility for an acceleration scheme in which high-brightness electron bunches are injected into the wave to undergo a strong acceleration. The long-size nature of the acceleration bucket with respect to the short length of the electron bunches can be handled in a more robust manner in comparison with the case when micrometric waves are employed

Noise Induced Phenomena in the Dynamics of Two Competing Species

Noise through its interaction with the nonlinearity of the living systems can give rise to counter-intuitive phenomena. In this paper we shortly review noise induced effects in different ecosystems, in which two populations compete for the same resources. We also present new results on spatial patterns of two populations, while modeling real distributions of anchovies and sardines. The transient dynamics of these ecosystems are analyzed through generalized Lotka-Volterra equations in the presence of multiplicative noise, which models the interaction between the species and the environment. We find noise induced phenomena such as quasi-deterministic oscillations, stochastic resonance, noise delayed extinction, and noise induced pattern formation. In addition, our theoretical results are validated with experimental findings. Specifically the results, obtained by a coupled map lattice model, well reproduce the spatial distributions of anchovies and sardines, observed in a marine ecosystem. Moreover, the experimental dynamical behavior of two competing bacterial populations in a meat product and the probability distribution at long times of one of them are well reproduced by a stochastic microbial predictive model.Comment: 23 pages, 8 figures; to be published in Math. Model. Nat. Phenom. (2016

\u3cem\u3eIn vivo\u3c/em\u3e Imaging of Human Cone Photoreceptor Inner Segments

Purpose. An often overlooked prerequisite to cone photoreceptor gene therapy development is residual photoreceptor structure that can be rescued. While advances in adaptive optics (AO) retinal imaging have recently enabled direct visualization of individual cone and rod photoreceptors in the living human retina, these techniques largely detect strongly directionally-backscattered (waveguided) light from normal intact photoreceptors. This represents a major limitation in using existing AO imaging to quantify structure of remnant cones in degenerating retina. Methods. Photoreceptor inner segment structure was assessed with a novel AO scanning light ophthalmoscopy (AOSLO) differential phase technique, that we termed nonconfocal split-detector, in two healthy subjects and four subjects with achromatopsia. Ex vivo preparations of five healthy donor eyes were analyzed for comparison of inner segment diameter to that measured in vivo with split-detector AOSLO. Results. Nonconfocal split-detector AOSLO reveals the photoreceptor inner segment with or without the presence of a waveguiding outer segment. The diameter of inner segments measured in vivo is in good agreement with histology. A substantial number of foveal and parafoveal cone photoreceptors with apparently intact inner segments were identified in patients with the inherited disease achromatopsia. Conclusions. The application of nonconfocal split-detector to emerging human gene therapy trials will improve the potential of therapeutic success, by identifying patients with sufficient retained photoreceptor structure to benefit the most from intervention. Additionally, split-detector imaging may be useful for studies of other retinal degenerations such as AMD, retinitis pigmentosa, and choroideremia where the outer segment is lost before the remainder of the photoreceptor cell

Evaluation of an in-capillary approach for performing quantitative cytochrome P450 activity studies

An automated in-capillary assay requiring very small quantities of reagents was developed for performing in vitro cytochrome P450 (CYP450) drug metabolism studies. The approach is based on the following: (i) hydrodynamic introduction of nanoliter volumes of substrate and enzyme solutions in the sandwich mode, within a capillary; (ii) mixing the reagents by diffusion across the interfaces between the injected solutions; (iii) collection of the capillary content at the end of the in-capillary assay; and (iv) off-line analysis of the incubation mixture by ultrahigh pressure liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). After optimizing the injection sequence of the reagents, the in-capillary approach was applied to the quantitative determination of the kinetics of drug metabolism reactions catalyzed by three CYP450 isozymes involved in human drug metabolism: CYP1A2, CYP2D6, and CYP3A4. It was demonstrated that this in-capillary method was able to provide similar kinetic parameters for CYP450 activity (e.g., Michaelis constants and turnover values) as the classical in vitro method, with a drastic reduction of reagent consumption. Injection setups used for in-capillary CYP450 assay

PREDICTORS OF DRINKING BEHAVIOUR AMONG ADOLESCENTS AND YOUNG ADULTS: A NEW PSYCHOSOCIAL CONTROL PERSPECTIVE

This find is registered at Portable Antiquities of the Netherlands with number PAN-0002525

The Glycolytic Pathway as a Target for Novel Onco-Immunology Therapies in Pancreatic Cancer

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal forms of human cancer, characterized by unrestrained progression, invasiveness and treatment resistance. To date, there are limited curative options, with surgical resection as the only effective strategy, hence the urgent need to discover novel therapies. A platform of onco-immunology targets is represented by molecules that play a role in the reprogrammed cellular metabolism as one hallmark of cancer. Due to the hypoxic tumor microenvironment (TME), PDA cells display an altered glucose metabolism—resulting in its increased uptake—and a higher glycolytic rate, which leads to lactate accumulation and them acting as fuel for cancer cells. The consequent acidification of the TME results in immunosuppression, which impairs the antitumor immunity. This review analyzes the genetic background and the emerging glycolytic enzymes that are involved in tumor progression, development and metastasis, and how this represents feasible therapeutic targets to counteract PDA. In particular, as the overexpressed or mutated glycolytic enzymes stimulate both humoral and cellular immune responses, we will discuss their possible exploitation as immunological targets in anti-PDA therapeutic strategies