Transient Thermal Analysis of Intense Proton Beam Loss on a Kicker Magnet Conductor Plate

The Super Proton Synchrotron SPS will be used as injector for the Large Hadron Collider LHC and needs adaptation to meet LHC requirements. The SPS injection kicker magnets MKP will undergo important modifications to comply with the requirements on magnetic field rise-time and ripple. The injection kicker presently installed has a return conductor of beryllium to minimise the risk of metal evaporation from its surface due to heating caused by beam impact. In the context of refurbishing the MKP to satisfy LHC requirements these conductors need replacement, preferably with a less delicate material. This article presents the transient thermal analysis of energy deposition caused by beam loss on the conductor plate. The expected time structure of the beam is taken into account. Simulations comparing different conductor materials have been performed, leading to the result that a significantly cheaper and fully inoffensive titanium alloy can satisfy the needs

Beam Loss Damage in a Wire Septum

The beams for the Large Hadron Collider LHC will be extracted from the Super Proton Synchrotron SPS in points LSS4 (Long Straight Section) and LSS6 in fast mode during a single turn. For this purpose a new fast extraction will be designed in LSS4. In LSS6 the existing slow extraction channel needs modification such that it can provide fast extracted beam for LHC, while continuing to provide the West Experimental Area with long spills. Both fast and slow extraction must be available from the same point, although in an interleaved mode. This imposes the retention of the thin electrostatic wire septum ZS actually in use. The present article focuses on the effect of total beam loss in the electrostatic septum as it could occur e.g. due to a kicker magnet failure during fast extraction in LSS6. Then the entire SPS beam of 4.13 10^13 protons would impinge on the septum wires. The damage caused by the resulting electromagnetic and hadronic particle showers is determined and the need to protect the ZS is evaluated.<BR

The RF Cycle of the PIMMS Medical Synchrotron

This paper presents the design of the RF cycle of the medical synchrotron of the PIMMS (Proton-Ion Medical Machine Study) hosted at CERN. The cycle comprises adiabatic trapping, acceleration and RF gymnastics, for either protons or fully stripped carbon ions. The injection energy is 20 MeV for protons and 7 MeV/u for carbon. Maximum extraction energies are 250 MeV for protons and 400 MeV/u for carbon ions. The cycle duration is less than 1 s, with a maximum magnetic field ramp below 3 T/s. The simulations show that the beam stays inside the aperture of the machine, and that, theoretically, there are no longitudinal losses. At the end of the cycle, the beam is ready for extraction with a Dp/p = 0.4 %. The peak RF voltage is 3 kV and the frequency ranges from 0.4 to 3 MHz

The RF Cycle of the PIMMS Synchrotron

This paper deals with the study of the rf cycle of the synchrotron of the Proton-Ion Medical Machine Study (PIMMS) hosted at CERN. The cycle comprises the adiabatic trapping, the acceleration and the rf gymnastics, both for protons and fully stripped carbon ions. The injection energy is 20 MeV for protons and 7 MeV/u for carbon. The maximum extraction energies are 250 MeV for protons and 400 MeV/u for carbon ions. The reserved time is less than 1 s, with a maximum magnetic field ramp of less than 3 T/s. The simulations show that the beam stays inside the aperture of the machine, and that there are no longitudinal losses. At the end of the cycle the beam is ready for extraction with a Dp/p of 0.4 %. The peak rf voltage is 3 kV and the frequency range is from 0.49 to 2.85 MHz

Tomographic Measurements of Longitudinal Phase Space Density

Tomography is now a very broad topic with a wealth of algorithms for the reconstruction of both qualitative and quantitative images. One of the simplest algorithms has been modified to take into accou nt the non-linearity of large-amplitude synchrotron motion. This permits the accurate reconstruction of longitudinal phase space density from one-dimensional bunch profile data. The method is a hybrid one which incorporates particle tracking, and considerable effort has been invested to optimize the computer code so that it may also be compiled to exploit parallel architectures efficiently. A selec tion of the results obtained at different CERN accelerators is presented. The starting-point in each case is simply a "mountain range" of digitized bunch profiles

Lessons from LIMK1 enzymology and their impact on inhibitor design

LIM domain kinase 1 (LIMK1) is a key regulator of actin dynamics. It is thereby a potential therapeutic target for the prevention of fragile X syndrome and amyotrophic lateral sclerosis. Herein, we use X-ray crystallography and activity assays to describe how LIMK1 accomplishes substrate specificity, to suggest a unique ‘rock-and-poke’ mechanism of catalysis and to explore the regulation of the kinase by activation loop phosphorylation. Based on these findings, a differential scanning fluorimetry assay and a RapidFire mass spectrometry activity assay were established, leading to the discovery and confirmation of a set of small-molecule LIMK1 inhibitors. Interestingly, several of the inhibitors were inactive towards the closely related isoform LIMK2. Finally, crystal structures of the LIMK1 kinase domain in complex with inhibitors (PF-477736 and staurosporine, respectively) are presented, providing insights into LIMK1 plasticity upon inhibitor binding

The New SPS Extraction Channel for LHC and CNGS

The Large Hadron Collider (LHC) and CERN Neutrino to Gran Sasso (CNGS) projects require the construction of a new fast-extraction system in the long straight section LSS4 of the Super Proton Synchrotron (SPS) at CERN. A conventional DC septum magnet will be used, in conjunction with the installation of horizontal and vertical extraction bumpers, main quadrupoles with enlarged apertures, extraction kicker magnets and additional hardware protection, instrumentation, controls and electronics. The extraction channel must be able to accept the bright LHC proton beam at 450 GeV/c, and also the high intensity, large emittance fixed target CNGS proton beam at the nominal 400 GeV/c extraction momentum. This paper describes the extraction channel to be installed in 2003, and shows how the requirements for both the LHC and CNGS project can be met

Eur J Human Genet

Heterozygous missense mutations in the serine-threonine kinase receptor BMPR1B result typically in brachydactyly type A2 (BDA2), whereas mutations in the corresponding ligand GDF5 cause brachydactyly type C (BDC). Mutations in the GDF inhibitor Noggin (NOG) or activating mutations in GDF5 cause proximal symphalangism (SYM1). Here, we describe a novel mutation in BMPR1B (R486Q) that is associated with either BDA2 or a BDC/SYM1-like phenotype. Functional investigations of the R486Q mutation were performed and compared with the previously reported BDA2-causing mutation R486W and WT BMPR1B. Overexpression of the mutant receptors in chicken micromass cultures resulted in a strong inhibition of chondrogenesis with the R486Q mutant, showing a stronger effect than the R486W mutant. To investigate the consequences of the BMPR1B mutations on the intracellular signal transduction, we used stably transfected C2C12 cells and measured the activity of SMAD-dependent and SMAD-independent pathways. SMAD activation after stimulation with GDF5 was suppressed in both mutants. Alkaline phosphatase induction showed an almost complete loss of activation by both mutants. Our data extend the previously known mutational and phenotypic spectrum associated with mutations in BMPR1B. Disturbances of NOG-GDF5-BMPR1B signaling cascade can result in similar clinical manifestations depending on the quantitative effect and mode of action of the specific mutations within the same functional pathway

High Blood Flow Into the Femur Indicates Elevated Aerobic Capacity in Synapsids Since the Synapsida-Sauropsida Split

Varanids are the only non-avian sauropsids that are known to approach the warm-blooded mammals in stamina. Furthermore, a much higher maximum metabolic rate (MMR) gives endotherms (including birds) higher stamina than crocodiles, turtles, and non-varanid lepidosaurs. This has led researchers to hypothesize that mammalian endothermy evolved as a second step after the acquisition of elevated MMR in non-mammalian therapsids from a plesiomorphic state of low metabolic rates. In recent amniotes, MMR correlates with the index of blood flow into the femur (Qi), which is calculated from femoral length and the cross-sectional area of the nutrient foramen. Thus, Qi may serve as an indicator of MMR range in extinct animals. Using the Qi proxy and phylogenetic eigenvector maps, here we show that elevated MMRs evolved near the base of Synapsida. Non-mammalian synapsids, including caseids, edaphosaurids, sphenacodontids, dicynodonts, gorgonopsids, and non-mammalian cynodonts, show Qi values in the range of recent endotherms and varanids, suggesting that raised MMRs either evolved in synapsids shortly after the Synapsida-Sauropsida split in the Mississippian or that the low MMR of lepidosaurs and turtles is apomorphic, as has been postulated for crocodiles.Peer Reviewe

Ontogeny of synaptophysin and synaptoporin in the central nervous system

The expression of the synaptic vesicle antigens synaptophysin (SY) and synaptoporin (SO) was studied in the rat striatum, which contains a nearly homogeneous population of GABAergic neurons. In situ hybridization revealed high levels of SY transcripts in the striatal anlage from embryonic day (E) 14 until birth. In contrast. SO hybridization signals were low, and no immunoreactive cell bodies were detected at these stages of development. At E 14, SY-immunoreactivity was restricted to perikarya. In later prenatal stages of development SY-immunoreactivity appeared in puncta (identified as terminals containing immunostained synaptic vesicles), fibers, thick fiber bundles and ‘patches’. In postnatal and adult animals, perikarya of striatal neurons exhibited immunoreaction for SO; ultrastructurally SO antigen was found in the Golgi apparatus and in multivesicular bodies. SO-positive boutons were rare in the striatum. In the neuropil, numerous presynaptic terminals positive for SY were observed. Our data indicate that the expression of synaptic vesicle proteins in GABAergic neurons of the striatum is developmentally regulated. Whereas SY is prevalent during embryonic development, SO is the major synaptic vesicle antigen expressed postnatally by striatal neurons which project to the globus pallidus and the substantia nigra. In contrast synapses of striatal afferents (predominantly from cortex, thalamus and substantia nigra) contain SY