Giving meaning to alternative methods to animal testing

The 3 rd edition of the advanced theoretical-training course \u201c Giving meaning to alternative methods to animal testing \u201d was held in Genoa on July 6-7, 2017. The theoretical modules included talks by specialists from companies engaged in the field of advanced in vitro technologies, who offered participants the possibility to try out their technologies in the training modules

Experimental evidence of intrabeam scattering in a free-electron laser driver

Abstract The effect of multiple small-angle Coulomb scattering, or intrabeam scattering (IBS) is routinely observed in electron storage rings over the typical damping time scale of milliseconds. So far, IBS has not been observed in single pass electron accelerators because charge density orders of magnitude higher than in storage rings would be needed. We show that such density is now available at high brightness electron linacs for free-electron lasers (FELs). We report measurements of the beam energy spread in the FERMI linac in the presence of the microbunching instability, which are consistent with a revisited IBS model for single pass systems. We also show that neglecting the hereby demonstrated effect of IBS in the parameter range typical of seeded VUV and soft x-ray FELs, results in too conservative a facility design, or failure to realise the accessible potential performance. As an example, an optimization of the FERMI parameters driven by an experimentally benchmarked model, opens the door to the extension of stable single spectral line emission to the water window (2.3–4.4 nm), with far-reaching implications for experiments in a variety of disciplines, ranging from physics and chemistry to biology and material sciences, and including nonlinear x-ray optics based on the four-wave-mixing approach.</jats:p

New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background

<p>Abstract</p> <p>Background</p> <p>Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS) have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis</p> <p>Results</p> <p>Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31%) and from 69.1 to 86.2% (average 76.6%) respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%). This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg158cys; hepatic lipase -480 C/T; endothelial nitric oxide synthase 690 C/T and glu298asp; vitamin K-dependent coagulation factor seven arg353glu, glycoprotein Ia/IIa 873 G/A and E-selectin ser128arg.</p> <p>Conclusion</p> <p>This study provides an alternative and reliable method to approach complex diseases. Indeed, the application of a novel artificial intelligence-based method offers a new insight into genetic markers of sporadic ALS pointing out the existence of a strong genetic background.</p

Polymorphisms in folate-metabolizing genes, chromosome damage, and risk of Down syndrome in Italian women: identification of key factors using artificial neural networks

<p>Abstract</p> <p>Background</p> <p>Studies in mothers of Down syndrome individuals (MDS) point to a role for polymorphisms in folate metabolic genes in increasing chromosome damage and maternal risk for a Down syndrome (DS) pregnancy, suggesting complex gene-gene interactions. This study aimed to analyze a dataset of genetic and cytogenetic data in an Italian group of MDS and mothers of healthy children (control mothers) to assess the predictive capacity of artificial neural networks assembled in TWIST system in distinguish consistently these two different conditions and to identify the variables expressing the maximal amount of relevant information to the condition of being mother of a DS child.</p> <p>The dataset consisted of the following variables: the frequency of chromosome damage in peripheral lymphocytes (BNMN frequency) and the genotype for 7 common polymorphisms in folate metabolic genes (<it>MTHFR </it>677C>T and 1298A>C, <it>MTRR </it>66A>G, <it>MTR </it>2756A>G, <it>RFC1 </it>80G>A and <it>TYMS </it>28bp repeats and 1494 6bp deletion). Data were analysed using TWIST system in combination with supervised artificial neural networks, and a semantic connectivity map.</p> <p>Results</p> <p>TWIST system selected 6 variables (BNMN frequency, <it>MTHFR </it>677TT, <it>RFC1 </it>80AA, <it>TYMS </it>1494 6bp +/+, <it>TYMS </it>28bp 3R/3R and <it>MTR </it>2756AA genotypes) that were subsequently used to discriminate between MDS and control mothers with 90% accuracy. The semantic connectivity map provided important information on the complex biological connections between the studied variables and the two conditions (being MDS or control mother).</p> <p>Conclusions</p> <p>Overall, the study suggests a link between polymorphisms in folate metabolic genes and DS risk in Italian women.</p

Microbunching instability characterization via temporally modulated laser pulses

High-brightness electron bunches, such as those generated and accelerated in free-electron lasers (FELs), can develop small-scale structure in the longitudinal phase space. This causes variations in the slice energy spread and current profile of the bunch which then undergo amplification, in an effect known as the microbunching instability. By imposing energy spread modulations on the bunch in the low-energy section of an accelerator, using an undulator and a modulated laser pulse in the centre of a dispersive chicane, it is possible tomanipulate the bunch longitudinal phase space. This allows for the control and study of the instability in unprecedented detail. We report measurements and analysis of such modulated electron bunches in the 2Dspectro-temporal domain at the FERMI FEL, for three different bunch compression schemes. We also perform corresponding simulations of these experiments and show that the codes are indeed able to reproduce the measurements across a wide spectral range. This detailed experimental verification of the ability of codes to capture the essential beam dynamics of the microbunching instability will benefit the design and performance of future FELs

Microbunching instability characterization via temporally modulated laser pulses

High-brightness electron bunches, such as those generated and accelerated in free-electron lasers (FELs), can develop small-scale structure in the longitudinal phase space. This causes variations in the slice energy spread and current profile of the bunch which then undergo amplification, in an effect known as the microbunching instability. By imposing energy spread modulations on the bunch in the low-energy section of an accelerator, using an undulator and a modulated laser pulse in the center of a dispersive chicane, it is possible to manipulate the bunch longitudinal phase space. This allows for the control and study of the instability in unprecedented detail. We report measurements and analysis of such modulated electron bunches in the 2D spectrotemporal domain at the Fermi FEL, for three different bunch compression schemes. We also perform corresponding simulations of these experiments and show that the codes are indeed able to reproduce the measurements across a wide spectral range. This detailed experimental verification of the ability of codes to capture the essential beam dynamics of the microbunching instability will benefit the design and performance of future FELs

Effective Theory Approach to the Spontaneous Breakdown of Lorentz Invariance

We generalize the coset construction of Callan, Coleman, Wess and Zumino to theories in which the Lorentz group is spontaneously broken down to one of its subgroups. This allows us to write down the most general low-energy effective Lagrangian in which Lorentz invariance is non-linearly realized, and to explore the consequences of broken Lorentz symmetry without having to make any assumptions about the mechanism that triggers the breaking. We carry out the construction both in flat space, in which the Lorentz group is a global spacetime symmetry, and in a generally covariant theory, in which the Lorentz group can be treated as a local internal symmetry. As an illustration of this formalism, we construct the most general effective field theory in which the rotation group remains unbroken, and show that the latter is just the Einstein-aether theory.Comment: 45 pages, no figures

A new method for measuring angle-resolved phases in photoemission

Quantum mechanically, photoionization can be fully described by the complex photoionization amplitudes that describe the transition between the ground state and the continuum state. Knowledge of the value of the phase of these amplitudes has been a central interest in photoionization studies and newly developing attosecond science, since the phase can reveal important information about phenomena such as electron correlation. We present a new attosecond-precision interferometric method of angle-resolved measurement for the phase of the photoionization amplitudes, using two phase-locked Extreme Ultraviolet pulses of frequency $\omega$ and $2\omega$, from a Free-Electron Laser. Phase differences $\Delta \tilde \eta$ between one- and two-photon ionization channels, averaged over multiple wave packets, are extracted for neon $2p$ electrons as a function of emission angle at photoelectron energies 7.9, 10.2, and 16.6 eV. $\Delta \tilde \eta$ is nearly constant for emission parallel to the electric vector but increases at 10.2 eV for emission perpendicular to the electric vector. We model our observations with both perturbation and \textit{ab initio} theory, and find excellent agreement. In the existing method for attosecond measurement, Reconstruction of Attosecond Beating By Interference of Two-photon Transitions (RABBITT), a phase difference between two-photon pathways involving absorption and emission of an infrared photon is extracted. Our method can be used for extraction of a phase difference between single-photon and two-photon pathways and provides a new tool for attosecond science, which is complementary to RABBITT