Time series analysis of Coulomb collisions in a beam dynamics simulation

Abstract In this paper, a time series analysis of collisional effects in a numerical simulation of a coasting beam transverse dynamics is presented. The simulation performs a numerical integration of the Hamilton's equations of a two-dimensional system of particles, describing the transverse dynamics of the beam. Then, an analysis of the time series generated has been applied in order to describe the dynamics of the system by means of the mean field equations, with the addition of a stochastic process in order to model Coulomb collisions

Comparing different approaches for generating random numbers device-independently using a photon pair source

What is the most efficient way to generate random numbers device-independently using a photon pair source based on spontaneous parametric down conversion (SPDC)? We consider this question by comparing two implementations of a detection-loophole-free Bell test. In particular, we study in detail a scenario where a heralded single photon source (HSPS) is used to herald path-entangled states, i.e. entanglement between two spatial modes sharing a single photon and where non-locality is revealed using photon counting preceded by small displacement operations. We start by giving a theoretical description of such a measurement. We then show how to optimize the Bell-CHSH violation through a non-perturbative calculation, taking the main experimental imperfections into account. We finally bound the amount of randomness that can be extracted and compare it to the one obtained with the conventional scenario using photon pairs entangled e.g. in polarization and analyzed through photon counting. While the former requires higher overall detection efficiencies, it is far more efficient in terms of both the entropy per experimental run and the rate of random bit generation.Comment: 12 pages, 5 figure

Targeting a phospho-STAT3-miRNAs pathway improves vesicular hepatic steatosis in an in vitro and in vivo model

Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. Although genetic predisposition and epigenetic factors contribute to the development of NAFLD, our understanding of the molecular mechanism involved in the pathogenesis of the disease is still emerging. Here we investigated a possible role of a microRNAs-STAT3 pathway in the induction of hepatic steatosis. Differentiated HepaRG cells treated with the fatty acid sodium oleate (fatty dHepaRG) recapitulated features of liver vesicular steatosis and activated a cell-autonomous inflammatory response, inducing STAT3-Tyrosine-phosphorylation. With a genome-wide approach (Chromatin Immunoprecipitation Sequencing), many phospho-STAT3 binding sites were identified in fatty dHepaRG cells and several STAT3 and/or NAFLD-regulated microRNAs showed increased expression levels, including miR-21. Innovative CARS (Coherent Anti-Stokes Raman Scattering) microscopy revealed that chemical inhibition of STAT3 activity decreased lipid accumulation and deregulated STAT3-responsive microRNAs, including miR-21, in lipid overloaded dHepaRG cells. We were able to show in vivo that reducing phospho-STAT3-miR-21 levels in C57/BL6 mice liver, by long-term treatment with metformin, protected mice from aging-dependent hepatic vesicular steatosis. Our results identified a microRNAs-phosphoSTAT3 pathway involved in the development of hepatic steatosis, which may represent a molecular marker for both diagnosis and therapeutic targeting

Cyclooxygenase-2 inhibitors. 1,5-diarylpyrrol-3-acetic esters with enhanced inhibitory activity toward cyclooxygenase-2 and improved cyclooxygenase-2/cyclooxygenase-1 selectivity.

he important role of cyclooxygenase-2 (COX-2) in the pathogenesis of inflammation and side effect limitations of current COX-2 inhibitor drugs illustrates a need for the design of new compounds based on alternative structural templates. We previously reported a set of substituted 1,5-diarylpyrrole derivatives, along with their inhibitory activity toward COX enzymes. Several compounds proved to be highly selective COX-2 inhibitors and their affinity data were rationalized through docking simulations. In this paper, we describe the synthesis of new 1,5-diarylpyrrole derivatives that were assayed for their in vitro inhibitory effects toward COX isozymes. Among them, the ethyl-2-methyl-5-[4-(methylsulfonyl)phenyl]-1-[3-fluorophenyl]-1H-pyrrol-3- acetate (1d), which was the most potent and COX-2 selective compound, also showed a very interesting in vivo anti-inflammatory and analgesic activity, laying the foundations for developing new lead compounds that could be effective agents in the armamentarium for the management of inflammation and pain

Stacking Simulations for Compton Positron sources of Future Linear Colliders

The Compton positron source of a future linear collider must obtain the target bunch population by accumulating a large number of positron packets, arriving either in a number of bursts from a ‘Compton ring’, with intermediate damping of the scattering electron beam, or quasicontinually from a ‘Compton energy recovery linac’. We present simulation results for the longitudinal stacking of Compton positrons in the ILC damping ring (DR) and the CLIC pre-damping ring (PDR), discussing parameter optimization, stacking efficiency, possible further improvements, and outstanding questions

The ROK kinase N-acetylglucosamine kinase uses a sequential random enzyme mechanism with successive conformational changes upon each substrate binding.

This is the final version. Available on open access from Elsevier via the DOI in this record. N-acetyl-d-glucosamine (GlcNAc) is a major component of bacterial cell walls. Many organisms recycle GlcNAc from the cell wall or metabolize environmental GlcNAc. The first step in GlcNAc metabolism is phosphorylation to GlcNAc-6-phosphate. In bacteria, the ROK family kinase N-acetylglucosamine kinase (NagK) performs this activity. Although ROK kinases have been studied extensively, no ternary complex showing the two substrates has yet been observed. Here, we solved the structure of NagK from the human pathogen Plesiomonas shigelloides in complex with GlcNAc and the ATP analog AMP-PNP. Surprisingly, PsNagK showed distinct conformational changes associated with the binding of each substrate. Consistent with this, the enzyme showed a sequential random enzyme mechanism. This indicates that the enzyme acts as a coordinated unit responding to each interaction. Our molecular dynamics modeling of catalytic ion binding confirmed the location of the essential catalytic metal. Additionally, site-directed mutagenesis confirmed the catalytic base and that the metal-coordinating residue is essential. Together, this study provides the most comprehensive insight into the activity of a ROK kinase.Biotechnology and Biological Sciences Research Council (BBSRC)National Science FoundationUK Research and Innovatio