A Low Charge Demonstration of Electron Pulse Compression for the CLIC RF Power Source

The CLIC (Compact Linear Collider) RF power source is based on a new scheme of electron pulse compression and bunch frequency multiplication using injection by transverse RF deflectors into an isochronous ring. In this paper, we describe the modifications needed in the present LEP Pre-Injector (LPI) complex at CERN in order to perform a low-charge test of the scheme. The design of the injector (including the new thermionic gun), of the modified linac, of the matched injection line, and of the isochronous ring lattice, are presented. The results of preliminary isochronicity measurements made on the present installation are also discussed.Comment: 3 pages, 5 figures, submitted to the LINAC 2000 Conferenc

CLIC simulations from the start of the linac to the interaction point

Simulations for linear colliders are traditionally performed separately for the different sub-systems, like damping ring, bunch compressor, linac, and beam delivery. The beam properties are usually passed from one sub-system to the other via bunch charge, RMS transverse emittances, RMS bunch length, average energy and RMS energy spread. It is implicitly assumed that the detailed 6D correlations in the beam distribution are not relevant for the achievable luminosity. However, it has recently been shown that those correlations can have a strong effect on the beam-beam interaction. We present first results on CLIC simulations that integrate linac, beam delivery, and beam-beam interaction. These integrated simulations also allow a better simulation of time-dependent effects, like ground perturbations and interference between several beam-based feedbacks

The lattice of the CERN Large Hadron Collider

The lattice of the CERN Large Hadron Collider is designed with 23 regular cells per arc, each containing 6 tightly packed 14.2 m long dipoles. This allows to reach 7 TeV per beam with a dipole field of 8.4 Tesla. There are four experimental insertions, two of which are devoted to high luminosity experiments with ± 23 m of free space for the detector. The other two experimental insertions are combined with injection. The value of ß* at the interaction points is tunable from 6 m at injection to 0.5 m in collision. The energy deposition in the inner triplets is carefully reduced to sustain the nominal luminosity of 1034 cm-2s-1. Two insertions are devoted to collect the halo particles with large emittance and momentum spread surrounding the beam core: escaping rates of the protons are estimated to be less than 4·106 sec-1m-1. Finally, one insertion is used to extract the particles in the vertical direction with a minimized deflecting strength

PspF-binding domain PspA1-144 and the PspA·F complex: New insights into the coiled-coil-dependent regulation of AAA+ proteins.

Phage shock protein A (PspA) belongs to the highy conserved PspA/IM30 family and is a key component of the stress inducible Psp system in Escherichia coli. One of its central roles is the regulatory interaction with the transcriptional activator of this system, the σ54 enhancer binding protein PspF, a member of the AAA+ protein family. The PspA/F regulatory system has been intensively studied and serves as a paradigm for AAA+ enzyme regulation by trans-acting factors. However, the molecular mechanism of how exactly PspA controls the activity of PspF and hence σ54-dependent expression of the psp genes is still unclear. To approach this question, we identified the minimal PspF-interacting domain of PspA, solved its structure, determined its affinity to PspF and the dissociation kinetics, identified residues that are potentially important for PspF regulation and analyzed effects of their mutation on PspF in vivo and in vitro. Our data indicate that several characteristics of AAA+ regulation in the PspA·F complex resemble those of the AAA+ unfoldase ClpB, with both proteins being regulated by a structurally highly conserved coiled-coil domain. The convergent evolution of both regulatory domains points to a general mechanism to control AAA+ activity for divergent physiological tasks via coiled-coil domains

Modification of the association between paroxetine serum concentration and SERT-occupancy by ABCB1 (P-glycoprotein) polymorphisms in major depressive disorder

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) exert substantial variability in effectiveness in patients with major depressive disorder (MDD), with up to 50-60% not achieving adequate response. Elucidating pharmacokinetic factors that explain this variability is important to increase treatment effectiveness. OBJECTIVES: To examine potential modification of the relationship between paroxetine serum concentration (PSC) and serotonin transporter (SERT)-occupancy by single nucleotide polymorphisms (SNPs) of the ABCB1 gene, coding for the P-glycoprotein (P-gp) pump, in MDD patients. To investigate the relationship between ABCB1 SNPs and clinical response. METHODS: Patients had MDD and received paroxetine 20 mg/day. We measured PSC after 6 weeks. We quantified SERT-occupancy with SPECT imaging (n = 38) and measured 17-item Hamilton Depression Rating Scale (HDRS17)-scores at baseline and after 6 wee

Growth, polymorphism, and spatially controlled surface immobilization of biotinylated variants of IAPP(21-27) fibrils

FWN – Publicaties zonder aanstelling Universiteit Leide

Initial results from beam commissioning of the LHC beam dump system

Initial commissioning of the LHC beam dump system with beam took place in August and September 2008. The preparation, setting-up and the tests performed are described together with results of the extractions of beam into the dump lines. Analysis of the first detailed aperture measurements of the extraction channels and kicker performance derived from dilution sweep shapes are presented. The performance of the other equipment subsystems is summarised, in particular that of the dedicated dump system beam instrumentation

OPTICS FLEXIBILITY AND MATCHING AT LHC INJECTION

Abstract An excellent match between the SPS, the several kilometres long transfer lines and the LHC will be required to minimise emittance blow-up at injection. Several optics changes in the SPS and the LHC injection insertions had to be accommodated in the design phase. The new 3-phase collimation system in the transfer lines results in additional phase advance constraints. It will be important to maintain some tuning range for the LHC commissioning phase and to accommodate possible further optics changes. We analyse the requirements, the constraints, the current status and options to enhance the optics flexibility

Association of genetic variants of the histamine H1 and muscarinic M3 receptors with BMI and HbA1c values in patients on antipsychotic medication

Rationale: Antipsychotic affinity for the histamine H1 receptor and the muscarinic M3 receptor have been associated with the side effects weight gain, and development of diabetes, respectively. Objectives: We investigated polymorphisms of the histamine H1 (HRH1) and muscarinic acetylcholine receptor M3 (CHRM3) receptor genes for an association with body mass index (BMI) and glycated hemoglobin (HbA1c). Methods: We included 430 Caucasian patients with a non-affective psychotic disorder using antipsychotics for at least 3 months. Primary endpoints of the study were cross-sectionally measured BMI and HbA1c; secondary endpoints were obesity and hyperglycaemia. Two single-nucleotide polymorphisms (SNPs) in the HRH1 gene, rs346074 and rs346070, and one SNP in the CHRM3 gene, rs3738435, were genotyped. Our primary hypothesis in this study was an interaction between genotype on BMI and antipsychotic affinity for the H1 and M3 receptor. Results: A significant association of interaction between haplotype rs346074-rs346070 and BMI (p value 0.025) and obesity (p value 0.005) in patients using high-H1 affinity antipsychotics versus patients using low-H1 affinity antipsychotics was found. There was no association of CHRM3 gene variant rs3738435 with BMI, and we observed no association with HbA1c or hyperglycaemia in any of the variants. Conclusions: This study, for the first time, demonstrates a significant association between HRH1 variants and BMI in patients with a psychotic disorder using antipsychotics. In future, genotyping of HRH1 variants may help predicting weight gain in patients using antipsychotics

SUMOylation of Syntaxin1A regulates presynaptic endocytosis

Neurotransmitter release from the presynaptic terminal is under very precise spatial and temporal control. Following neurotransmitter release, synaptic vesicles are recycled by endocytosis and refilled with neurotransmitter. During the exocytosis event leading to release, SNARE proteins provide most of the mechanical force for membrane fusion. Here, we show one of these proteins, Syntaxin1A, is SUMOylated near its C-terminal transmembrane domain in an activity-dependent manner. Preventing SUMOylation of Syntaxin1A reduces its interaction with other SNARE proteins and disrupts the balance of synaptic vesicle endo/exocytosis, resulting in an increase in endocytosis. These results indicate that SUMOylation regulates the emerging role of Syntaxin1A in vesicle endocytosis, which in turn, modulates neurotransmitter release and synaptic function