Evolution of a beam dynamics model for the transport lines in a proton therapy facility

Despite the fact that the first-order beam dynamics models allow an approximated evaluation of the beam properties, their contribution is essential during the conceptual design of an accelerator or beamline. However, during the commissioning some of their limitations appear in the comparison against measurements. The extension of the linear model to higher order effects is, therefore, demanded. In this paper, the effects of particle-matter interaction have been included in the model of the transport lines in the proton therapy facility at the Paul Scherrer Institut (PSI) in Switzerland. To improve the performance of the facility, a more precise model was required and has been developed with the multi-particle open source beam dynamics code called OPAL (Object oriented Particle Accelerator Library). In OPAL, the Monte Carlo simulations of Coulomb scattering and energy loss are performed seamless with the particle tracking. Beside the linear optics, the influence of the passive elements (e.g. degrader, collimators, scattering foils and air gaps) on the beam emittance and energy spread can be analysed in the new model. This allows for a significantly improved precision in the prediction of beam transmission and beam properties. The accuracy of the OPAL model has been confirmed by numerous measurements.Comment: 17 pages, 19 figure

A Geometrical Method of Decoupling

The computation of tunes and matched beam distributions are essential steps in the analysis of circular accelerators. If certain symmetries - like midplane symmetrie - are present, then it is possible to treat the betatron motion in the horizontal, the vertical plane and (under certain circumstances) the longitudinal motion separately using the well-known Courant-Snyder theory, or to apply transformations that have been described previously as for instance the method of Teng and Edwards. In a preceeding paper it has been shown that this method requires a modification for the treatment of isochronous cyclotrons with non-negligible space charge forces. Unfortunately the modification was numerically not as stable as desired and it was still unclear, if the extension would work for all thinkable cases. Hence a systematic derivation of a more general treatment seemed advisable. In a second paper the author suggested the use of real Dirac matrices as basic tools to coupled linear optics and gave a straightforward recipe to decouple positive definite Hamiltonians with imaginary eigenvalues. In this article this method is generalized and simplified in order to formulate a straightforward method to decouple Hamiltonian matrices with eigenvalues on the real and the imaginary axis. It is shown that this algebraic decoupling is closely related to a geometric "decoupling" by the orthogonalization of the vectors $\vec E$, $\vec B$ and $\vec P$, that were introduced with the so-called "electromechanical equivalence". We present a structure-preserving block-diagonalization of symplectic or Hamiltonian matrices, respectively. When used iteratively, the decoupling algorithm can also be applied to n-dimensional systems and requires ${\cal O}(n^2)$ iterations to converge to a given precision.Comment: 13 pages, 1 figur

Synthetic Cell-Based Immunotherapies for Neurologic Diseases

The therapeutic success and widespread approval of genetically engineered T cells for a variety of hematologic malignancies spurred the development of synthetic cell-based immunotherapies for CNS lymphoma, primary brain tumors, and a growing spectrum of nononcologic disease conditions of the nervous system. Chimeric antigen receptor effector T cells bear the potential to deplete target cells with higher efficacy, better tissue penetration, and greater depth than antibody-based cell depletion therapies. In multiple sclerosis and other autoimmune disorders, engineered T-cell therapies are being designed and currently tested in clinical trials for their safety and efficacy to eliminate pathogenic B-lineage cells. Chimeric autoantibody receptor T cells expressing a disease-relevant autoantigen as cell surface domains are designed to selectively deplete autoreactive B cells. Alternative to cell depletion, synthetic antigen-specific regulatory T cells can be engineered to locally restrain inflammation, support immune tolerance, or efficiently deliver neuroprotective factors in brain diseases in which current therapeutic options are very limited. In this article, we illustrate prospects and bottlenecks for the clinical development and implementation of engineered cellular immunotherapies in neurologic diseases

Inhibition of glyoxylate conversion to oxalate in cultured human cells by the carbonyl-scavenging drug, aminoguanidine

Calcium oxalate is the most frequent cause of kidney stones, and is responsible for the damage to kidneys and other organs observed in inherited disorders of oxalate metabolism. Most oxalate produced in the body is derived from its metabolic precursor, glyoxylate. Thus, any means of scavenging glyoxylate to a non-toxic product, thereby diverting it away from oxalate synthesis, has considerable therapeutic implications. Here we show that aminoguanidine, a compound with a proven safety record and used for many years to prevent long-term complications of diabetes, binds glyoxylate covalently and reduces its conversion to oxalate by human liver- and lymphocyte-derived cell lines by >90%. We propose that scavenging glyoxylate with aminoguanidine or its congeners may provide a means of reducing oxalate production in vivo, and advocate the tissue culture system described here as a convenient means for testing such agents in vitro. A serendipitous finding to emerge from our study was the abiotic and strongly pH-dependent formation of oxalate from ascorbate, which has implications for the contribution of ascorbate to urine oxalate excretion

The roles of segmental and tandem gene duplication in the evolution of large gene families in Arabidopsis thaliana

BACKGROUND: Most genes in Arabidopsis thaliana are members of gene families. How do the members of gene families arise, and how are gene family copy numbers maintained? Some gene families may evolve primarily through tandem duplication and high rates of birth and death in clusters, and others through infrequent polyploidy or large-scale segmental duplications and subsequent losses. RESULTS: Our approach to understanding the mechanisms of gene family evolution was to construct phylogenies for 50 large gene families in Arabidopsis thaliana, identify large internal segmental duplications in Arabidopsis, map gene duplications onto the segmental duplications, and use this information to identify which nodes in each phylogeny arose due to segmental or tandem duplication. Examples of six gene families exemplifying characteristic modes are described. Distributions of gene family sizes and patterns of duplication by genomic distance are also described in order to characterize patterns of local duplication and copy number for large gene families. Both gene family size and duplication by distance closely follow power-law distributions. CONCLUSIONS: Combining information about genomic segmental duplications, gene family phylogenies, and gene positions provides a method to evaluate contributions of tandem duplication and segmental genome duplication in the generation and maintenance of gene families. These differences appear to correspond meaningfully to differences in functional roles of the members of the gene families

Making limb and nadir measurements comparable: A common volume study of PMC brightness observed by Odin OSIRIS and AIM CIPS

Combining limb and nadir satellite observations of Polar Mesospheric Clouds (PMCs) has long been recognized as problematic due to differences in observation geometry, scattering conditions, and retrieval approaches. This study offers a method of comparing PMC brightness observations from the nadir-viewing Aeronomy of Ice in the Mesosphere (AIM) Cloud Imaging and Particle Size (CIPS) instrument and the limb-viewing Odin Optical Spectrograph and InfraRed Imaging System (OSIRIS). OSIRIS and CIPS measurements are made comparable by defining a common volume for overlapping OSIRIS and CIPS observations for two northern hemisphere (NH) PMC seasons: NH08 and NH09. We define a scattering intensity quantity that is suitable for either nadir or limb observations and for different scattering conditions. A known CIPS bias is applied, differences in instrument sensitivity are analyzed and taken into account, and effects of cloud inhomogeneity and common volume definition on the comparison are discussed. Not accounting for instrument sensitivity differences or inhomogeneities in the PMC field, the mean relative difference in cloud brightness (CIPS - OSIRIS) is −102 ± 55%. The differences are largest for coincidences with very inhomogeneous clouds that are dominated by pixels that CIPS reports as non-cloud points. Removing these coincidences, the mean relative difference in cloud brightness reduces to −6 ± 14%. The correlation coefficient between the CIPS and OSIRIS measurements of PMC brightness variations in space and time is remarkably high, at 0.94. Overall, the comparison shows excellent agreement despite different retrieval approaches and observation geometries