The Influence of Density Distribution on the Stability of Beams

We examine the effect of various density distributions in four-dimensional phase space and their projections in real and velocity space on the stability of continuous beams in alternating-gradient transport lines using particle-following computer simulations. We discuss the susceptibility of three different distributions (Kapchinskii-Vladimirskii, bicylinder, and thermal) to third- and higher-order mode instabilities. These distributions are all uniform in real space, but their velocity distributions are different; they also react differently to structure resonances. Velocity distributions of high-current beams tend to evolve to a peaked Gaussian-like form. Is there a specific velocity distribution that is stable and, therefore, the preferred injection distribution for minimizing emittance growth. Forced smoothness or uniformity in real space is necessary for setting up particle simulations of high-current beams so that spurious charge-redistribution emittance growth can be avoided. Is forced smoothness also desirable in four dimensions for continuous beams and possibly in six dimensions for bunched beams. We consider these and related questions

Complementary split-ring resonator-coupled traveling wave accelerating structure

In this paper, we present theoretical and simulation-based analyses of a novel, normal-conducting, multiple-cell, traveling wave accelerating structure. Instead of the conventional circular apertures, we utilize asymmetric complementary split-ring resonators to couple pillbox cavities and bring the phase velocity below that of the speed of light in vacuo. We show that this architecture exhibits a low, negative, group velocity and that the 0 through π modes decrease in order of frequency—in contrast to conventional electrically coupled structures in which the 0 mode has the lowest frequency and the π mode the highest. We illustrate the efficacy of the proposed design via electromagnetic and particle simulation results for a four-cell structure operating around 1.9 GHz. Results are given for operation in the π, 2π/3, and π/3 modes. Our design achieves accelerating gradients of around 3.3  MV/m and a cavity voltage of 0.594 MV for an applied rf power of 82 kW (π mode). The accelerating gradients achieved are up to 3.3 times that of a conventional circular aperture-coupled design with the same phase velocity, rf excitation power, operating frequency, mode type, and number of cells

Obstacles on the way to the clinical visualisation of beta cells: looking for the Aeneas of molecular imaging to navigate between Scylla and Charybdis

For more than a decade, researchers have been trying to develop non-invasive imaging techniques for the in vivo measurement of viable pancreatic beta cells. However, in spite of intense research efforts, only one tracer for positron emission tomography (PET) imaging is currently under clinical evaluation. To many diabetologists it may remain unclear why the imaging world struggles to develop an effective method for non-invasive beta cell imaging (BCI), which could be useful for both research and clinical purposes. Here, we provide a concise overview of the obstacles and challenges encountered on the way to such BCI, in both native and transplanted islets. We discuss the major difficulties posed by the anatomical and cell biological features of pancreatic islets, as well as the chemical and physical limits of the main imaging modalities, with special focus on PET, SPECT and MRI. We conclude by indicating new avenues for future research in the field, based on several remarkable recent results

Lessons learned from additional research analyses of unsolved clinical exome cases

BACKGROUND: Given the rarity of most single-gene Mendelian disorders, concerted efforts of data exchange between clinical and scientific communities are critical to optimize molecular diagnosis and novel disease gene discovery. METHODS: We designed and implemented protocols for the study of cases for which a plausible molecular diagnosis was not achieved in a clinical genomics diagnostic laboratory (i.e. unsolved clinical exomes). Such cases were recruited to a research laboratory for further analyses, in order to potentially: (1) accelerate novel disease gene discovery; (2) increase the molecular diagnostic yield of whole exome sequencing (WES); and (3) gain insight into the genetic mechanisms of disease. Pilot project data included 74 families, consisting mostly of parent-offspring trios. Analyses performed on a research basis employed both WES from additional family members and complementary bioinformatics approaches and protocols. RESULTS: Analysis of all possible modes of Mendelian inheritance, focusing on both single nucleotide variants (SNV) and copy number variant (CNV) alleles, yielded a likely contributory variant in 36% (27/74) of cases. If one includes candidate genes with variants identified within a single family, a potential contributory variant was identified in a total of ~51% (38/74) of cases enrolled in this pilot study. The molecular diagnosis was achieved in 30/63 trios (47.6%). Besides this, the analysis workflow yielded evidence for pathogenic variants in disease-associated genes in 4/6 singleton cases (66.6%), 1/1 multiplex family involving three affected siblings, and 3/4 (75%) quartet families. Both the analytical pipeline and the collaborative efforts between the diagnostic and research laboratories provided insights that allowed recent disease gene discoveries (PURA, TANGO2, EMC1, GNB5, ATAD3A, and MIPEP) and increased the number of novel genes, defined in this study as genes identified in more than one family (DHX30 and EBF3). CONCLUSION: An efficient genomics pipeline in which clinical sequencing in a diagnostic laboratory is followed by the detailed reanalysis of unsolved cases in a research environment, supplemented with WES data from additional family members, and subject to adjuvant bioinformatics analyses including relaxed variant filtering parameters in informatics pipelines, can enhance the molecular diagnostic yield and provide mechanistic insights into Mendelian disorders. Implementing these approaches requires collaborative clinical molecular diagnostic and research efforts

Experimental investigation of random noise-induced beam degradation in high-intensity accelerators using a linear Paul trap

A random noise-induced beam degradation that could affect intense beam transport over long propagation distances has been experimentally investigated by making use of the transverse beam dynamics equivalence between an alternating-gradient focusing system and a linear Paul trap system. For the present study, machine imperfections in the quadrupole focusing lattice are considered, which are emulated by adding small random noise on the voltage waveform of the quadrupole electrodes in the Paul trap. It is observed that externally driven noise continuously increases the rms radius, transverse emittance, and nonthermal tail of the trapped charge bunch almost linearly with the duration of the noise. The combined effects of collective modes and colored noise are also investigated and compared with numerical simulationsclose3

Expert consensus document: Clinical and molecular diagnosis, screening and management of Beckwith-Wiedemann syndrome: an international consensus statement.

Beckwith-Wiedemann syndrome (BWS), a human genomic imprinting disorder, is characterized by phenotypic variability that might include overgrowth, macroglossia, abdominal wall defects, neonatal hypoglycaemia, lateralized overgrowth and predisposition to embryonal tumours. Delineation of the molecular defects within the imprinted 11p15.5 region can predict familial recurrence risks and the risk (and type) of embryonal tumour. Despite recent advances in knowledge, there is marked heterogeneity in clinical diagnostic criteria and care. As detailed in this Consensus Statement, an international consensus group agreed upon 72 recommendations for the clinical and molecular diagnosis and management of BWS, including comprehensive protocols for the molecular investigation, care and treatment of patients from the prenatal period to adulthood. The consensus recommendations apply to patients with Beckwith-Wiedemann spectrum (BWSp), covering classical BWS without a molecular diagnosis and BWS-related phenotypes with an 11p15.5 molecular anomaly. Although the consensus group recommends a tumour surveillance programme targeted by molecular subgroups, surveillance might differ according to the local health-care system (for example, in the United States), and the results of targeted and universal surveillance should be evaluated prospectively. International collaboration, including a prospective audit of the results of implementing these consensus recommendations, is required to expand the evidence base for the design of optimum care pathways

Correction: Expanding the clinical phenotype of individuals with a 3-bp in-frame deletion of the NF1 gene (c.2970_2972del): an update of genotype–phenotype correlation

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