Towards Quantitative Simulations of High Power Proton Cyclotrons

PSI operates a cyclotron based high intensity proton accelerator routinely at an average beam power of 1.3MW. With this power the facility is at the worldwide forefront of high intensity proton accelerators. The beam current is practically limited by losses at extraction and the resulting activation of accelerator components. Further intensity upgrades and new projects aiming at an even higher average beam power, are only possible if the relative losses can be lowered in proportion, thus keeping absolute losses at a constant level. Maintaining beam losses at levels allowing hands-on maintenance is a primary challenge in any high power proton machine design and operation. In consequence, predicting beam halo at these levels is a great challenge and will be addressed in this paper. High power hadron driver have being used in many disciplines of science and, a growing interest in the cyclotron technology for high power hadron drivers are being observed very recently. This report will briefly introduce OPAL, a tool for precise beam dynamics simulations including 3D space charge. One of OPAL's flavors (OPAL-cycl) is dedicated to high power cyclotron modeling and is explained in greater detail. We then explain how to obtain initial conditions for our PSI Ring cyclotron which still delivers the world record in beam power of 1.3 MW continuous wave (cw). Several crucial steps are explained necessary to be able to predict tails at the level of 3\sigma ... 4\sigma in the PSI Ring cyclotron. We compare our results at the extraction with measurements, obtained with a 1.18 MW cw production beam. Based on measurement data, we develop a simple linear model to predict beam sizes of the extracted beam as a function of intensities and confirm the model with simulations.Comment: Corrections and new figur

Исследования по разработке методики определения примеси таллия в кадмии особой чистоты методом АПН

Проводились исследования по разработке методики определения Tl в Cd особой чистоты. Изучалось влияние избытка Pb и Cd на определение Tl. Предложена методика определения Tl в кадмии особой чистоты. Чувствительность методики 0,000001%

Beam Dynamics in High Intensity Cyclotrons Including Neighboring Bunch Effects: Model, Implementation and Application

Space charge effects, being one of the most significant collective effects, play an important role in high intensity cyclotrons. However, for cyclotrons with small turn separation, other existing effects are of equal importance. Interactions of radially neighboring bunches are also present, but their combined effects has not yet been investigated in any great detail. In this paper, a new particle in cell based self-consistent numerical simulation model is presented for the first time. The model covers neighboring bunch effects and is implemented in the three-dimensional object-oriented parallel code OPAL-cycl, a flavor of the OPAL framework. We discuss this model together with its implementation and validation. Simulation results are presented from the PSI 590 MeV Ring Cyclotron in the context of the ongoing high intensity upgrade program, which aims to provide a beam power of 1.8 MW (CW) at the target destination

SLAMF Receptor Expression Identifies an Immune Signature That Characterizes Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology, linked to alterations in both the innate and the adaptive immune system. Due to the heterogeneity of the clinical presentation, the diagnosis of SLE remains complicated and is often made years after the first symptoms manifest, delaying treatment, and worsening the prognosis. Several studies have shown that signaling lymphocytic activation molecule family (SLAMF) receptors are aberrantly expressed and dysfunctional in SLE immune cells, contributing to the altered cellular function observed in these patients. The aim of this study was to determine whether altered co-/expression of SLAMF receptors on peripheral blood mononuclear cells (PBMC) identifies SLE characteristic cell populations. To this end, single cell mass cytometry and bioinformatic analysis were exploited to compare SLE patients to healthy and autoimmune diseases controls. First, the expression of each SLAMF receptor on all PBMC populations was investigated. We observed that SLAMF1+ B cells (referred to as SLEB1) were increased in SLE compared to controls. Furthermore, the frequency of SLAMF4+ monocytes and SLAMF4+ NK were inversely correlated with disease activity, whereas the frequency SLAMF1+ CD4+ TDEM cells were directly correlated with disease activity. Consensus clustering analysis identified two cell clusters that presented significantly increased frequency in SLE compared to controls: switch memory B cells expressing SLAMF1, SLAMF3, SLAMF5, SLAMF6 (referred to as SLESMB) and circulating T follicular helper cells expressing the same SLAMF receptors (referred to as SLEcTFH). Finally, the robustness of the identified cell populations as biomarkers for SLE was evaluated through ROC curve analysis. The combined measurement of SLEcTFH and SLEB1 or SLESMB cells identified SLE patients in 90% of cases. In conclusion, this study identified an immune signature for SLE based on the expression of SLAMF receptors on PBMC, further highlighting the involvement of SLAMF receptors in the pathogenesis of SLE

Loss of Extracellular Signal-Regulated Kinase 1/2 in the Retinal Pigment Epithelium Leads to RPE65 Decrease and Retinal Degeneration.

Recent work suggested that the activity of extracellular signal-regulated kinase 1/2 (ERK1/2) is increased in the retinal pigment epithelium (RPE) of age-related macular degeneration (ARMD) patients and therefore could be an attractive therapeutic target. Notably, ERK1/2 pathway inhibitors are used in cancer therapy, with severe and noncharacterized ocular side effects. To decipher the role of ERK1/2 in RPE cells, we conditionally disrupted the Erk1 and Erk2 genes in mouse RPE. The loss of ERK1/2 activity resulted in a significant decrease in the level of RPE65 expression, a decrease in ocular retinoid levels concomitant with low visual function, and a rapid disorganization of RPE cells, ultimately leading to retinal degeneration. Our results identify the ERK1/2 pathway as a direct regulator of the visual cycle and a critical component of the viability of RPE and photoreceptor cells. Moreover, our results caution about the need for a very fine adjustment of kinase inhibition in cancer or ARMD treatment in order to avoid ocular side effects

Extracellular matrix formation after transplantation of human embryonic stem cell-derived cardiomyocytes

Transplantation of human embryonic stem cell-derived cardiomyocytes (hESC-CM) for cardiac regeneration is hampered by the formation of fibrotic tissue around the grafts, preventing electrophysiological coupling. Investigating this process, we found that: (1) beating hESC-CM in vitro are embedded in collagens, laminin and fibronectin, which they bind via appropriate integrins; (2) after transplantation into the mouse heart, hESC-CM continue to secrete collagen IV, XVIII and fibronectin; (3) integrin expression on hESC-CM largely matches the matrix type they encounter or secrete in vivo; (4) co-transplantation of hESC-derived endothelial cells and/or cardiac progenitors with hESC-CM results in the formation of functional capillaries; and (5) transplanted hESC-CM survive and mature in vivo for at least 24 weeks. These results form the basis of future developments aiming to reduce the adverse fibrotic reaction that currently complicates cell-based therapies for cardiac disease, and to provide an additional clue towards successful engraftment of cardiomyocytes by co-transplanting endothelial cells

The caudal regeneration blastema is an accumulation of rapidly proliferating stem cells in the flatworm Macrostomum lignano

Background: Macrostomum lignano is a small free-living flatworm capable of regenerating all body parts posterior of the pharynx and anterior to the brain. We quantified the cellular composition of the caudal-most body region, the tail plate, and investigated regeneration of the tail plate in vivo and in semithin sections labeled with bromodeoxyuridine, a marker for stem cells (neoblasts) in S-phase. Results: The tail plate accomodates the male genital apparatus and consists of about 3,100 cells, about half of which are epidermal cells. A distinct regeneration blastema, characterized by a local accumulation of rapidly proliferating neoblasts and consisting of about 420 cells (excluding epidermal cells), was formed 24 hours after amputation. Differentiated cells in the blastema were observed two days after amputation (with about 920 blastema cells), while the male genital apparatus required four to five days for full differentiation. At all time points, mitoses were found within the blastema. At the place of organ differentiation, neoblasts did not replicate or divide. After three days, the blastema was made of about 1420 cells and gradually transformed into organ primordia, while the proliferation rate decreased. The cell number of the tail plate, including about 960 epidermal cells, was restored to 75% at this time point. Conclusion: Regeneration after artificial amputation of the tail plate of adult specimens of Macrostomum lignano involves wound healing and the formation of a regeneration blastema. Neoblasts undergo extensive proliferation within the blastema. Proliferation patterns of S-phase neoblasts indicate that neoblasts are either determined to follow a specific cell fate not before, but after going through S-phase, or that they can be redetermined after S-phase. In pulse-chase experiments, dispersed distribution of label suggests that S-phase labeled progenitor cells of the male genital apparatus undergo further proliferation before differentiation, in contrast to progenitor cells of epidermal cells. Mitotic activity and proliferation within the blastema is a feature of M. lignano shared with many other regenerating animals