Fast chopper system for high intensity proton beams

In der vorliegenden Arbeit wird ein schnelles Choppersystem für einen hochintensiven niederenergetischen Protonenstrahl untersucht. Das Choppersystem wird in der Niedrigenergiesektion (LEBT) der Frankfurter Neutronenquelle FRANZ eingesetzt. Der Treiberstrahl hat dort eine Energie von 120 keV und eine Intensität von bis zu 200 mA Protonen. Gefordert ist die Erzeugung eines gepulsten Strahls mit einem 50 bis 100 ns langen Pulsplateau und einer Wiederholrate von 250 kHz. Nach der Diskussion verschiedener Chopperkonzepte wird der Einsatz eines Kickersystems vorgeschlagen. Magnetische und elektrische Kicker werden im Hinblick auf Geometrie, Ablenkfelder, Strahldynamik, Emittanzwachstum, Leistungsbedarf sowie Betrieb im Schwingungs- oder im Pulsmodus untersucht. Die Realisierung des Choppersystems wird mit Hilfe von numerischen Simulationen und Vorexperimenten geprüft. Ein eigens dazu entwickelter Particle-in-cell (PIC)-Code wird vorgestellt. Er erlaubt die Simulation von Vielteilchen-Prozessen in zeitabhängigen Kickerfeldern unter Berücksichtigung der Effekte der Sekundärelektronen. Die Vorexperimente für die Ansteuerung des Kickers werden präsentiert. Für den magnetischen Kicker wurde eine niederinduktive Testspule und für den elektrischen Kicker ein Transformator bestehend aus einem nanokristallinen Ringbandkern aufgebaut. Abschließend werden die beiden Systeme miteinander verglichen. Ein magnetischer Kicker ist auch bei hohen Strahlintensitäten weniger anfällig für Strahlverluste und kann ohne die Gefahr von Spannungsdurchschlägen betrieben werden. Bei den geforderten hohen Wiederholraten ist jedoch der Leistungsbedarf nicht annehmbar, so dass im Ausblick die Weiterentwicklung eines elektrischen Kickersystems vorgeschlagen wird.In the framework of this thesis a fast chopper system for a low energy high intensity proton beam was investigated. The chopper system will be installed in the Low Energy Beam Transport (LEBT) section of the Frankfurt Neutron Source facility (FRANZ), where the proton driver beam has an energy of 120 keV, with intensities up to 200 mA. The generation of a pulsed beam with a 50 to 100 ns flat top at a repetition rate of 250 kHz is required. After discussing different chopper concepts the use of a kicker system is proposed. Magnetic and electric kickers are characterized regarding geometry, deflecting fields, beam dynamics, emittance growth, power consumption and mode of operation i.e. pulsed or oscillatory. The design of the chopper system is studied using numerical simulations and pre-experiments. A Particle-in-cell (PIC) code developed for this purpose is presented. It allows the simulation of multi-particle scenarios in time-dependent kicker fields while considering the effects of secondary electrons. The pre-experiments for the driver of the kicker system are described. In the case of the magnetic kicker a low inductance test coil and in the case of the electric kicker a transformer consisting of a nanocrystalline tape wound core was constructed. Altogether, both systems are compared with each other. A magnetic kicker is less susceptible to beam losses and can be operated without risk of voltage breakdowns even at high beam intensities. But at the required high repetition rate the power consumption is not acceptable. Therefore the development of an electric kicker system is proposed

Detours increase local knowledge-Exploring the hidden benefits of self-control failure

Self-control enables people to override momentary thoughts, emotions, or impulses in order to pursue long-term goals. Good self-control is a predictor for health, success, and subjective well-being, as bad self-control is for the opposite. Therefore, the question arises why evolution has not endowed us with perfect self-control. In this article, we draw some attention to the hidden benefits of self-control failure and present a new experimental paradigm that captures both costs and benefits of self-control failure. In an experiment, participants worked on three consecutive tasks: 1) In a transcription task, we manipulated how much effortful self-control two groups of participants had to exert. 2) In a number-comparison task, participants of both groups were asked to compare numbers and ignore distracting neutral versus reward-related pictures. 3) After a pause for recreation, participants were confronted with an unannounced recognition task measuring whether they had incidentally encoded the distracting pictures during the previous number-comparison task. The results showed that participants who exerted a high amount of effortful self-control during the first task shifted their priorities and attention toward the distractors during the second self-control demanding task: The cost of self-control failure was reflected in worse performance in the number-comparison task. Moreover, the group which had exerted a high amount of self-control during the first task and showed self-control failure during the second task was better in the unannounced third task. The benefit of self-control failure during number comparison was reflected in better performance during the recognition task. However, costs and benefits were not specific for reward-related distractors but also occurred with neutral pictures. We propose that the hidden benefit of self-control failure lies in the exploration of distractors present during goal pursuit [...

Shedding light on the molecular and regulatory mechanisms of TLR4 signaling in endothelial cells under physiological and inflamed conditions

Toll-like receptor 4 (TLR4) are part of the innate immune system. They are capable of recognizing pathogen-associated molecular patterns (PAMPS) of microbes, and damage-associated molecular patterns (DAMPs) of damaged tissues. Activation of TLR4 initiates downstream signaling pathways that trigger the secretion of cytokines, type I interferons, and other pro-inflammatory mediators that are necessary for an immediate immune response. However, the systemic release of pro-inflammatory proteins is a powerful driver of acute and chronic inflammatory responses. Over the past decades, immense progress has been made in clarifying the molecular and regulatory mechanisms of TLR4 signaling in inflammation. However, the most common strategies used to study TLR4 signaling rely on genetic manipulation of the TLR4 or the treatment with agonists such as lipopolysaccharide (LPS) derived from the outer membrane of Gram-negative bacteria, which are often associated with the generation of irreversible phenotypes in the target cells or unintended cytotoxicity and signaling crosstalk due to off-target or pleiotropic effects. Here, optogenetics offers an alternative strategy to control and monitor cellular signaling in an unprecedented spatiotemporally precise, dose-dependent, and non-invasive manner. This review provides an overview of the structure, function and signaling pathways of the TLR4 and its fundamental role in endothelial cells under physiological and inflammatory conditions, as well as the advances in TLR4 modulation strategies

Gender specific expression of tumor suppressor PKCd versus oncogenic PKCn in renal cell carcinoma

Tumor incidence for renal cell carcinoma is two-fold higher in males than in females. Members of the protein kinase C (PKC) gene family have been shown to be relevant for carcinogenesis. However, little is known about a possible gender specific role of PKC in renal cell carcinoma (RCC). In this study, we quantified expression of eleven PKC-isoforms in clear cell RCCs (ccRCC) and in the corresponding normal renal tissue. A possible association of PKC-isoforms with gender of the patients was examined. Tissue specimens of 27 patients, 14 males and 13 females, with ccRCC and of the corresponding normal renal tissue were examined. Expression of PKC-isoforms were detected by Western blot analysis and quantified by computer-aided integration. In ccRCCs, as well as in the corresponding normal renal tissue, all PKC-isoforms except PKCy and 0 were detectable. Clear associations with gender of the patients were observed: (i) PKCd was reduced in tumor tissue of female patients (p = 0.023), but not of male patients (p = 0.198). (ii) A 3.6-fold enhanced expression of the oncogene PKC? was found in tumor tissue of female compared to male patients (p = 0.049). Gender specific differences in PKCd as well as PKCn expression suggest that different molecular mechanisms are relevant for carcinogenesis of ccRCC in male and female patients. This may become important for classification and treatment of ccRCC

An arbitrated quantum signature scheme

The general principle for a quantum signature scheme is proposed and investigated based on ideas from classical signature schemes and quantum cryptography. The suggested algorithm is implemented by a symmetrical quantum key cryptosystem and Greenberger-Horne-Zeilinger (GHZ) triplet states and relies on the availability of an arbitrator. We can guarantee the unconditional security of the algorithm, mostly due to the correlation of the GHZ triplet states and the use of quantum one-time pads.Comment: 10 pages, no figures. Phys. Rev. A 65, (In press

A new mechanism for mtDNA pathogenesis: impairment of post-transcriptional maturation leads to severe depletion of mitochondrial tRNA(Ser(UCN)) caused by T7512C and G7497A point mutations

We have studied the consequences of two homoplasmic, pathogenic point mutations (T7512C and G7497A) in the tRNA(Ser(UCN)) gene of mitochondrial (mt) DNA using osteosarcoma cybrids. We identified a severe reduction of tRNA(Ser(UCN)) to levels below 10% of controls for both mutations, resulting in a 40% reduction in mitochondrial protein synthesis rate and in a respiratory chain deficiency resembling that in the patients muscle. Aminoacylation was apparently unaffected. On non-denaturating northern blots we detected an altered electrophoretic mobility for G7497A containing tRNA molecules suggesting a structural impact of this mutation, which was confirmed by structural probing. By comparing in vitro transcribed molecules with native RNA in such gels, we also identified tRNA(Ser(UCN)) being present in two isoforms in vivo, probably corresponding to the nascent, unmodified transcripts co-migrating with the in vitro transcripts and a second, faster moving isoform corresponding to the mature tRNA. In cybrids containing either mutations the unmodified isoforms were severely reduced. We hypothesize that both mutations lead to an impairment of post-transcriptional modification processes, ultimately leading to a preponderance of degradation by nucleases over maturation by modifying enzymes, resulting in severely reduced tRNA(Ser(UCN)) steady state levels. We infer that an increased degradation rate, caused by disturbance of tRNA maturation and, in the case of the G7497A mutant, alteration of tRNA structure, is a new pathogenic mechanism of mt tRNA point mutations

Cardiorespiratory Fitness and Insulin Sensitivity in Overweight or Obese Subjects May Be Linked Through Intrahepatic Lipid Content

Objective: Low cardiorespiratory fitness predisposes to cardiovascular disease and type 2 diabetes mellitus in part independently of body weight. Given the close relationship between intrahepatic lipid content (IHL) and insulin sensitivity, we hypothesized that the direct relationship between fitness and insulin sensitivity may be explained by IHL. Research Design and Methods: We included 138 overweight to obese, otherwise healthy subjects (age: 43.6 +/- 8.9 yrs., body mass index: 33.8 +/- 4 kg/m(2)). Body composition was estimated by bio-impedance analyses. Abdominal fat distribution, intramyocellular, and intrahepatic lipid content were assessed by magnetic resonance spectroscopy and tomography. Incremental exercise testing was performed to estimate individual's cardiorespiratory fitness. Insulin sensitivity was determined during an oral glucose tolerance test. Results: For all subjects, cardiorespiratory fitness was related to insulin sensitivity (r=0.32, p<0.05), IHL (r=-0.27, p<0.05), visceral (r=-0.25, p<0.05) and total fat mass (r=-0.32, p<0.05), but not to intramyocellular lipids (r=-0.08, ns). Insulin sensitivity correlated significantly with all fat depots. In multivariate regression analyses, independent predictors of insulin sensitivity were IHL, visceral fat and fitness (r(2)=-0.43, p<0.01; r(2)=-0.34 and r(2)=0.29, p<0.05, respectively). However, the positive correlation between fitness and insulin sensitivity was abolished after adjustment for IHL (r=0.16, ns), whereas it remained significant when adjusted for visceral- or total body fat. Further, when subjects were grouped into high versus low IHL, insulin sensitivity was higher in those subjects with low IHL, irrespective of fitness levels. Conclusions: Our study suggests that the positive effect of increased cardiorespiratory fitness in overweight to obese subjects on insulin sensitivity may be mediated indirectly through IHL reduction

Advances in Production Management Systems: Issues, Trends, and Vision Towards 2030

Since its inception in 1978, the IFIP Working Group (WG) 5.7 on Advances in Production Management Systems (APMS) has played an active role in the fields of production and production management. The Working Group has focused on the conception, development, strategies, frameworks, architectures, processes, methods, and tools needed for the advancement of both fields. The associated standards created by the IFIP WG5.7 have always been impacted by the latest developments of scientific rigour, academic research, and industrial practices. The most recent of those developments involves the Fourth Industrial Revolution, which is having remarkable (r)evolutionary and disruptive changes in both the fields and the standards. These changes are triggered by the fusion of advanced operational and informational technologies, innovative operating and business models, as well as social and environmental pressures for more sustainable production systems. This chapter reviews past, current, and future issues and trends to establish a coherent vision and research agenda for the IFIP WG5.7 and its international community. The chapter covers a wide range of production aspects and resources required to design, engineer, and manage the next generation of sustainable and smart production systems.acceptedVersio

Energy deposition simulations for a damage experiment with superconducting sample coils

An experiment to study damage caused by the impact of 440 GeV/c protons on sample superconducting racetrack coils made from NbTi and Nb3Sn strands was recently carried out at CERN\u27s HiRadMat facility. This paper reports on the detailed Monte Carlo simulations performed with FLUKA and Geant4 to evaluate the energy deposition of the 440 GeV/c proton beam on the sample coils positioned in the experimental setup. using the measured beam parameters during the experiment. The measured hotspot temperatures and temperature gradients reached in the sample coils are presented and compared with the simulations. In addition, comparisons between the simulation results from FLUKA and Geant4 are discussed in detail