Genetic steps to organ laterality in zebrafish.

All internal organs are asymmetric along the left-right axis. Here we report a genetic screen to discover mutations which perturb organ laterality. Our particular focus is upon whether, and how, organs are linked to each other as they achieve their laterally asymmetric positions. We generated mutations by ENU mutagenesis and examined F3 progeny using a cocktail of probes that reveal early primordia of heart, gut, liver and pancreas. From the 750 genomes examined, we isolated seven recessive mutations which affect the earliest left-right positioning of one or all of the organs. None of these mutations caused discernable defects elsewhere in the embryo at the stages examined. This is in contrast to those mutations we reported previously (Chen et al., 1997) which, along with left-right abnormalities, cause marked perturbation in gastrulation, body form or midline structures. We find that the mutations can be classified on the basis of whether they perturb relationships among organ laterality. In Class 1 mutations, none of the organs manifest any left-right asymmetry. The heart does not jog to the left and normally leftpredominant BMP4 in the early heart tube remains symmetric. The gut tends to remain midline. There frequently is a remarkable bilateral duplication of liver and pancreas. Embryos with Class 2 mutations have organotypic asymmetry but, in any given embryo, organ positions can be normal, reversed or randomized. Class 3 reveals a hitherto unsuspected gene that selectively affects laterality of heart. We find that visceral organ positions are predicted by the direction of the preceding cardiac jog. We interpret this as suggesting that normally there is linkage between cardiac and visceral organ laterality. Class 1 mutations, we suggest, effectively remove the global laterality signals, with the consequence that organ positions are effectively symmetrical. Embryos with Class 2 mutations do manifest linkage among organs, but it may be reversed, suggesting that the global signals may be present but incorrectly orientated in some of the embryos. That laterality decisions of organs may be independently perturbed, as in the Class 3 mutation, indicates that there are distinctive pathways for reception and organotypic interpretation of the global signals

Phase space analysis of velocity bunched beams

Peak current represents a key demand for new generation electron beam photoinjectors. Many beam applications, such as free electron laser, inverse Compton scattering, terahertz radiation generation, have efficiencies strongly dependent on the bunch length and current. A method of beam longitudinal compression (called velocity bunching) has been proposed some years ago, based on beam longitudinal phase space rotation in a rf field potential. The control of such rotation can lead to a compression factor in excess of 10, depending on the initial longitudinal emittance. Code simulations have shown the possibility to fully compensate the transverse emittance growth during rf compression, and this regime has been experimentally proven recently at SPARC. The key point is the control of transverse beam plasma oscillations, in order to freeze the emittance at its lowest value at the end of compression. Longitudinal and transverse phase space distortions have been observed during the experiments, leading to asymmetric current profiles and higher final projected emittances. In this paper we discuss in detail the results obtained at SPARC in the regime of velocity bunching, analyzing such nonlinearities and identifying the causes. The beam degradation is discussed, both for slice and projected parameters. Analytical tools are derived to experimentally quantify the effect of such distortions on the projected emittanc

Self-amplified spontaneous emission for a single pass free-electron laser

SPARC (acronym of "Sorgente Pulsata ed Amplificata di Radiazione Coerente", i.e. Pulsed and Amplified Source of Coherent Radiation) is a single pass free-electron laser designed to obtain high gain amplification at a radiation wavelength of 500 nm. Self-amplified spontaneous emission has been observed driving the amplifier with the high-brightness beam of the SPARC linac. We report measurements of energy, spectra, and exponential gain. Experimental results are compared with simulations from several numerical codes

High-order-harmonic generation and superradiance in a seeded free-electron laser

Higher order harmonic generation in a free-electron laser amplifier operating in the superradiant regime [R.\u2009H. Dicke, Phys. Rev. 93, 99 (1954).] has been observed. Superradiance has been induced by seeding a single-pass amplifier with the second harmonic of a Ti:sapphire laser, generated in a \u3b2-Barium borate crystal, at seed intensities comparable to the free-electron laser saturation intensity. Pulse energy and spectral distributions of the harmonics up to the 11th order have been measured and compared with simulations

The conceptual design of CLARA, a novel fel test facility for ultra-short pulse generation

CLARA will be a novel FEL test facility focussed on the generation of ultra-short photon pulses with extreme levels of stability and synchronisation. The principal aim is to experimentally demonstrate that sub-cooperation length pulse generation with FELs is viable, and to compare the various schemes being championed. The results will translate directly to existing and future X-ray FELs, enabling them to generate attosecond pulses, thereby extending their science capabilities. This paper gives an overview of the motivation for CLARA, describes the facility design (reported in detail in the recently published Conceptual Design Report [1]) and proposed operating modes and summarises the proposed areas of FEL research

The practical Pomeron for high energy proton collimation

We present a model which describes proton scattering data from ISR to Tevatron energies, and which can be applied to collimation in high energy accelerators, such as the LHC and FCC. Collimators remove beam halo particles, so that they do not impinge on vulnerable regions of the machine, such as the superconducting magnets and the experimental areas. In simulating the effect of the collimator jaws it is crucial to model the scattering of protons at small momentum transfer t, as these protons can subsequently survive several turns of the ring before being lost. At high energies these soft processes are well described by Pomeron exchange models. We study the behaviour of elastic and single-diffractive dissociation cross sections over a wide range of energy, and show that the model can be used as a global description of the wide variety of high energy elastic and diffractive data presently available. In particular it models low mass diffraction dissociation, where a rich resonance structure is present, and thus predicts the differential and integrated cross sections in the kinematical range appropriate to the LHC. We incorporate the physics of this model into the beam tracking code MERLIN and use it to simulate the resulting loss maps of the beam halo lost in the collimators in the LHC

High-gain harmonic-generation free-electron laser seeded by harmonics generated in gas

The injection of a seed in a free-electron laser (FEL) amplifier reduces the saturation length and improves the longitudinal coherence. A cascaded FEL, operating in the high-gain harmonic-generation regime, allows us to extend the beneficial effects of the seed to shorter wavelengths. We report on the first operation of a high-gain harmonic-generation free-electron laser, seeded with harmonics generated in gas. The third harmonics of a Ti:sapphire laser, generated in a gas cell, has been amplified and up-converted to its second harmonic (\u3bbrad=133\u2009\u2009nm) in a FEL cascaded configuration based on a variable number of modulators and radiators. We studied the transition between coherent harmonic generation and superradiant regime, optimizing the laser performances with respect to the number of modulators and radiators

HE-LHC: The High-Energy Large Hadron Collider – Future Circular Collider Conceptual Design Report Volume 4

In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries