Nose cone mounted heat resistant antenna Patent

Nose cone mounted heat resistant antenna comprising plurality of adjacent layers of silica not introducing paths of high thermal conductivity through ablative shiel

Tabu Search for Frequency Assignment in Mobile Radio Networks

International audienc

Investigating the interaction between Organic Anion Transporter 1 and Ochratoxin A: an in silico structural study to depict early molecular events of substrate recruitment and the impact of single point mutations

Organic anion transporters (OATs) belong to a subgroup of the solute carrier 22 transporter family. OATs have a central role in xenobiotic disposition affecting the toxicokinetics of its substrates and inter-individual differences in their expression, activity and function impact both toxicokinetics and toxicodynamics. Amongst OATs, OAT1 (solute carrier family 22 member 6) is involved in the urinary excretion of many xenobiotics bringing substrates into renal proximal tubular cells which can then be secreted across the apical membrane into the tubule lumen. The mycotoxin ochratoxin A has been shown to have a high affinity for OAT1, which is an important renal transporter involved in its urinary excretion. Nowadays, molecular modeling techniques are widely applied to assess protein-ligand interactions and may provide a tool to depict the mechanistic of xenobiotic action be it toxicokinetics or toxicodynamics. This work provides a structured pipeline consisting of docking and molecular dynamic simulations to study OAT1-ligand interactions and the impact of OAT1 polymorphisms on such interactions. Such a computational structure-based analytical framework allowed to: i) model OAT1-substrate complex formation and depict the features correlating its sequence, structure and its capability to recruit substrates; and ii) investigate the impact of OAT1 missense mutations on substrate recruitment. Perspectives on applying such a structured pipeline to xenobiotic-metabolising enzymes are discussed

Editorial: EFSA calls for integrated and coordinated actions at EU and international levels to address global declines of pollinators

No abstract availabl

Investigating the interaction between organic anion transporter 1 and ochratoxin A: An in silico structural study to depict early molecular events of substrate recruitment and the impact of single point mutations

Organic anion transporters (OATs) belong to a subgroup of the solute carrier 22 transporter family. OATs have a central role in xenobiotic disposition affecting the toxicokinetics of its substrates and inter-individual differences in their expression, activity and function impact both toxicokinetics and toxicodynamics. Amongst OATs, OAT1 (solute carrier family 22 member 6) is involved in the urinary excretion of many xenobiotics bringing substrates into renal proximal tubular cells which can then be secreted across the apical membrane into the tubule lumen. The mycotoxin ochratoxin A has been shown to have a high affinity for OAT1, which is an important renal transporter involved in its urinary excretion. Nowadays, molecular modeling techniques are widely applied to assess protein-ligand interactions and may provide a tool to depict the mechanic of xenobiotic action be it toxicokinetics or toxicodynamics. This work provides a structured pipeline consisting of docking and molecular dynamic simulations to study OAT1-ligand interactions and the impact of OAT1 polymorphisms on such interactions. Such a computational structure-based analytical framework allowed to: i) model OAT1-substrate complex formation and depict the features correlating its sequence, structure and its capability to recruit substrates; and ii) investigate the impact of OAT1 missense mutations on substrate recruitment. Perspectives on applying such a structured pipeline to xenobiotic-metabolising enzymes are discussed

Integrating in silico models and read-across methods for predicting toxicity of chemicals: A step-wise strategy

Abstract In silico methods and models are increasingly used for predicting properties of chemicals for hazard identification and hazard characterisation in the absence of experimental toxicity data. Many in silico models are available and can be used individually or in an integrated fashion. Whilst such models offer major benefits to toxicologists, risk assessors and the global scientific community, the lack of a consistent framework for the integration of in silico results can lead to uncertainty and even contradictions across models and users, even for the same chemicals. In this context, a range of methods for integrating in silico results have been proposed on a statistical or case-specific basis. Read-across constitutes another strategy for deriving reference points or points of departure for hazard characterisation of untested chemicals, from the available experimental data for structurally-similar compounds, mostly using expert judgment. Recently a number of software systems have been developed to support experts in this task providing a formalised and structured procedure. Such a procedure could also facilitate further integration of the results generated from in silico models and read-across. This article discusses a framework on weight of evidence published by EFSA to identify the stepwise approach for systematic integration of results or values obtained from these "non-testing methods". Key criteria and best practices for selecting and evaluating individual in silico models are also described, together with the means to combining the results, taking into account any limitations, and identifying strategies that are likely to provide consistent results

High level indole signalling in Escherichia coli

Indole is a small signalling molecule, produced by many species of bacteria, including Escherichia coli. It is made by the enzyme tryptophanase, which converts tryptophan into indole, pyruvate and ammonia. Indole has diverse roles in E. coli, including regulation of biofilm formation, acid resistance and pathogenicity. In these cases, E. coli responds to a low, persistent level of indole (0.5-1 mM), similar to the concentration found in an E. coli culture supernatant in stationary phase (typically 0.3-0.8 mM). Recently, it has been shown that much higher concentrations of indole (3-5 mM) inhibit cell division by acting as an ionophore to dissipate the membrane potential. However the biological relevance of such high concentrations, and therefore these aspects of indole signalling, has been questioned. This work has investigated the role of indole signalling during entry into stationary phase, when indole production is quickly upregulated. The viability of non indole producing mutants was compared to wild-type indole producing cells. In the short term indole producers suffered a growth disadvantage, but in the long term they were significantly more viable than their indole non-producing counterparts. The addition of 1 mM indole to the indole non-producing culture failed to complement the phenotype. A hypothesis was developed that a high rate of indole production during stationary phase entry leads to a transient, high concentration of indole inside the cell. This regulates cell growth and division via the ionophore mechanism. The validity of this indole pulse signalling hypothesis was tested by measuring cellassociated indole. For a brief time during stationary phase entry cell-associated concentrations reached 60 mM. Cell-associated indole represents an average of indole in the cytoplasm and the cell membrane. It was shown that indole has an approximately 100-fold greater affinity for the cell membrane. 60 mM cell associated indole is equivalent to approximately 4 mM in the culture supernatant, suggesting that the indole ‘pulse’ is sufficient to inhibit growth and cell division on entry into stationary phase. The indole pulse was dependent on the stationary phase sigma factor, SigmaS, which increases tryptophanase expression on entry into stationary phase. This increased tryptophanase expression occurs immediately prior to increased indole production. The end of the pulse seems to correlate with the exhaustion of tryptophan in the growth medium

Generic physiologically based kinetic modelling for farm animals: Part I. Data collection of physiological parameters in swine, cattle and sheep

Abstract Physiologically based kinetic (PBK) models for farm animals are of growing interest in food and feed safety with key applications for regulated compounds including quantification of tissue concentrations, kinetic parameters and the setting of safe exposure levels on an internal dose basis. The development and application of these models requires data for physiological, anatomical and chemical specific parameters. Here, we present the results of a structured data collection of anatomical and physiological parameters in three key farm animal species (swine, cattle and sheep). We performed an extensive literature search and meta-analyses to quantify intra-species variability and associated uncertainty of the parameters. Parameters were collected for organ weights and blood flows in all available breeds from 110 scientific publications, of which 29, 48 and 33 for cattle, sheep, and swine, respectively. Organ weights were available in literature for all three species. Blood flow parameter values were available for all organs in sheep but were scarcer in swine and cattle. Furthermore, the parameter values showed a large intra-species variation. Overall, the parameter values and associated variability provide reference values which can be used as input for generic PBK models in these species

The design of an omnidirectional antenna system for the Apollo spacecraft

Omnidirectional radio antenna system design for Apollo command modul

Preventing the Interaction between Coronaviruses Spike Protein and Angiotensin I Converting Enzyme 2: An In Silico Mechanistic Case Study on Emodin as a Potential Model Compound

Emodin, a widespread natural anthraquinone, has many biological activities including health-protective and adverse effects. Amongst beneficial effects, potential antiviral activity against coronavirus responsible for the severe acute respiratory syndrome outbreak in 2002–2003 has been described associated with the inhibition of the host cells target receptors recognition by the viral Spike protein. However, the inhibition mechanisms have not been fully characterized, hindering the rational use of emodin as a model compound to develop more effective analogues. This work investigates emodin interaction with the Spike protein to provide a mechanistic explanation of such inhibition. A 3D molecular modeling approach consisting of docking simulations, pharmacophoric analysis and molecular dynamics was used. The plausible mechanism is described as an interaction of emodin at the protein–protein interface which destabilizes the viral protein-target receptor complex. This analysis has been extended to the Spike protein of the coronavirus responsible for the current pandemic hypothesizing emodin’s functional conservation. This solid knowledge-based foothold provides a possible mechanistic rationale of the antiviral activity of emodin as a future basis for the potential development of efficient antiviral cognate compounds. Data gaps and future work on emodin-related adverse effects in parallel to its antiviral pharmacology are explored