Design of the 7 MeV/u, 217 MHz Injector Linac for the Proposed Ion Beam Facility for Cancer Therapy at the Clinic in Heidelberg

A dedicated clinical synchrotron facility for cancer therapy using energetic proton and ion beams (C, He and O) has been designed at GSI for the Radiologische Universitaetsklinik at Heidelberg, Germany. The design of the injector linac is presented. Suitable ion sources are discussed and results of ion source test measurements are reported. The LEBT allows for switching between two ion sources. A short RFQ accelerates the ions from 8 keV/u to 400 keV/u. It is followed by a very compact beam matching section and a 3.8 m long IH-type drift tube linac for the acceleration to 7 MeV/u. Both rf structures are designed for a resonance frequency of 216.816 MHz and for ion mass-to-charge ratios up to A/q = 3 (12C4+, (H_3)+, 3He+, 16O6+).Comment: Contribution to the LINAC2000 Proceedings, Paper ID: MOD1

Auswirkungen der Landwirtschaft auf physikalische und chemische Funktionen Europäischer Torfböden

Torfböden bieten zahlreiche Funktionen: sie bilden den weltweit größten terrestrischen Kohlenstoffspeicher, stellen wichtige Nährstofffilter dar und erhöhen hydrologische Pufferkapazitäten. Torfböden sind in Mittel- und Nordeuropa zum überwiegenden Teil landwirtschaftlich genutzt. Kultivierung führt zu extremen Mineralisierungsraten der organischen Substanz und hohen THG-Emissionen. Die Anfälligigkeit für Bodensackung, Boden- und Wasserqualitätsverschlechterung und folglich Ernteausfall steigt. Das Ziel dieser Studie ist es, Auswirkungen des Agrarmanagements auf Funktionen von Torfböden in Europa zu analysieren. In Deutschland, den Niederlanden, Dänemark, Estland, Finnland und Schweden wurden standardisierte Bodenkartierungen, bodenphysikalische und -chemische Analysen, Grundwassermonitoring und Betriebsdatenerhebungen durchgeführt. Die Ergebnisse belegen einen starken Einfluss der bisherigen Bewirtschaftung auf die Funktionen von Torfböden in Europa. Torfböden unter intensiver Ackernutzung bieten im Vergleich zu extensiver und intensiver Grünlandnutzung die niedrigste Tragfähigkeit in den oberen 10 cm, welche eine erfolgreiche landwirtschaftliche Praxis auf Torfböden stark einschränkt. Der Unterschied lässt sich allein durch Wurzelstabilisierung erklären, da die Bodenverdichtung in den oberen 25cm unter Ackernutzung am höchsten ist. Hieraus folgt eine starke Verringerung der nutzbaren Feldkapazität und der gesättigten hydraulischen Leitfähigkeit, wodurch sich hydrologische Probleme wie Staunässe und Trockenstress, die häufig auf kultivierten Torfböden vorkommen, weiter intensivieren. Bodenkohlenstoffvorräte sinken deutlich mit steigender Nutzungsintensität und sind im Vergleich auf extensivem Grünland am höchsten. Dies wird bestätigt durch den Zersetzungsgrad, der hier am niedrigsten ist. Die Ergebnisse deuten auf eine starke Auswirkung des Managements auf Bodenkohlenstoffverluste und Torfkonservierung auf europäischer Ebene hin

PKS 0537-441: extended [O II] emission and a binary QSO?

We present high-resolution imaging and low-resolution spectroscopy of the BL Lac object PKS 0537-441 (z = 0.893) and its environment. The observations were designed to clarify, whether the properties of PKS 0537-441 are affected by gravitational microlensing, or whether PKS 0537-441 and its environment act as a lensing system itself. Our observations show that neither case seems to be likely. We did not find a galaxy along the line-of-sight to the BL Lac as claimed previously, our spectroscopy shows that none of the four closest companion galaxies is at high redshift. Two of the four nearby companion galaxies to PKS 0537-441 are within 200 km/s of the systemic velocity of the BL Lac (z = 0.892 and 0.895, respectively). The third companion galaxy is at higher redshift (z = 0.947). The fourth companion galaxy shows evidence of Mg II absorption redwards of its systemic velocity and is perhaps a mini low ionization BAL QSO at z = 0.885. If the latter can be confirmed, PKS 0537-441 is the first BL Lacertae object being a member of a binary Quasar. We also detected extended [O II] emission in the off-nuclear spectrum of PKS 05371-441, which is most likely due to photoionization from the active nucleus. Alternatively, the extended [O II] emission is due to jet-cloud interaction with the counterjet of PKS 0537-441. Our clustering analysis indicates that PKS 0537-441 is located in a cluster environment as rich as Abell type 0-1. This is supported by the detection of four galaxies in the field with similar redshifts as the BL Lac (Delta z < 0.002). We found serendipitously even more galaxies at somewhat higher redshifts (z = 0.9-1). Thus, PKS0537-441 might be located in front of a galaxy cluster at somewhat higher redshift or even be part of a large-scale structure with an extension towards the BL Lac.Comment: 13 pages, 9 figures, accepted for publication in A&

Successful bone marrow transplantation in a patient with DNA ligase IV deficiency and bone marrow failure

BACKGROUND: DNA Ligase IV deficiency syndrome is a rare autosomal recessive disorder caused by hypomorphic mutations in the DNA ligase IV gene (LIG4). The clinical phenotype shows overlap with a number of other rare syndromes, including Seckel syndrome, Nijmegen breakage syndrome, and Fanconi anemia. Thus the clinical diagnosis is often delayed and established by exclusion. METHODS: We describe a patient with pre- and postnatal growth retardation and dysmorphic facial features in whom the diagnoses of Seckel-, Dubowitz-, and Nijmegen breakage syndrome were variably considered. Cellular radiosensitivity in the absence of clinical manifestations of Ataxia telangiectasia lead to the diagnosis of DNA ligase IV (LIG4) deficiency syndrome, confirmed by compound heterozygous mutations in the LIG4 gene. At age 11, after a six year history of progressive bone marrow failure and increasing transfusion dependency the patient was treated with matched sibling donor hematopoetic stem cell transplantation (HSCT) using a fludarabine-based conditioning regimen without irradiation. RESULTS: The post-transplantation course was uneventful with rapid engraftment leading to complete and stable chimerism. Now at age 16, the patient has gained weight and is in good clinical condition. CONCLUSION: HSCT using mild conditioning without irradiation qualifies as treatment of choice in LIG4-deficient patients who have a matched sibling donor

Constant light enhances synchrony among circadian clock cells and promotes behavioral rhythms in VPAC(2)-signaling deficient mice

Individual neurons in the suprachiasmatic nuclei (SCN) contain an intracellular molecular clock and use intercellular signaling to synchronize their timekeeping activities so that the SCN can coordinate brain physiology and behavior. The neuropeptide vasoactive intestinal polypeptide (VIP) and its VPAC2 receptor form a key component of intercellular signaling systems in the SCN and critically control cellular coupling. Targeted mutations in either the intracellular clock or intercellular neuropeptide signaling mechanisms, such as VIP-VPAC2 signaling, can lead to desynchronization of SCN neuronal clocks and loss of behavioral rhythms. An important goal in chronobiology is to develop interventions to correct deficiencies in circadian timekeeping. Here we show that extended exposure to constant light promotes synchrony among SCN clock cells and the expression of ~24 h rhythms in behavior in mice in which intercellular signaling is disrupted through loss of VIP-VPAC2 signaling. This study highlights the importance of SCN synchrony for the expression of rhythms in behavior and reveals how non-invasive manipulations in the external environment can be used to overcome neurochemical communication deficits in this important brain system

Complex networks for climate model evaluation with application to statistical versus dynamical modeling of South American climate

Acknowledgments: This paper was developed within the scope of the IRTG 1740/TRP 2011/50151-0, funded by the DFG/FAPESP. Furthermore, this work has been financially supported by the Leibniz Society (project ECONS), and the Stordalen Foundation (JFD). For certain calculations, the software packages pyunicorn (Donges et al. 2013a) and igraph (Csa´rdi and Nepusz 2006) were used. The authors would like to thank Manoel F. Cardoso, Niklas Boers, and the reviewers for helpful comments on the manuscript. Open Access: This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Peer reviewedPostprin

A LOV Protein Modulates the Physiological Attributes of Xanthomonas axonopodis pv. citri Relevant for Host Plant Colonization

Recent studies have demonstrated that an appropriate light environment is required for the establishment of efficient vegetal resistance responses in several plant-pathogen interactions. The photoreceptors implicated in such responses are mainly those belonging to the phytochrome family. Data obtained from bacterial genome sequences revealed the presence of photosensory proteins of the BLUF (Blue Light sensing Using FAD), LOV (Light, Oxygen, Voltage) and phytochrome families with no known functions. Xanthomonas axonopodis pv. citri is a Gram-negative bacterium responsible for citrus canker. The in silico analysis of the X. axonopodis pv. citri genome sequence revealed the presence of a gene encoding a putative LOV photoreceptor, in addition to two genes encoding BLUF proteins. This suggests that blue light sensing could play a role in X. axonopodis pv. citri physiology. We obtained the recombinant Xac-LOV protein by expression in Escherichia coli and performed a spectroscopic analysis of the purified protein, which demonstrated that it has a canonical LOV photochemistry. We also constructed a mutant strain of X. axonopodis pv. citri lacking the LOV protein and found that the loss of this protein altered bacterial motility, exopolysaccharide production and biofilm formation. Moreover, we observed that the adhesion of the mutant strain to abiotic and biotic surfaces was significantly diminished compared to the wild-type. Finally, inoculation of orange (Citrus sinensis) leaves with the mutant strain of X. axonopodis pv. citri resulted in marked differences in the development of symptoms in plant tissues relative to the wild-type, suggesting a role for the Xac-LOV protein in the pathogenic process. Altogether, these results suggest the novel involvement of a photosensory system in the regulation of physiological attributes of a phytopathogenic bacterium. A functional blue light receptor in Xanthomonas spp. has been described for the first time, showing an important role in virulence during citrus canker disease

Neuropeptide Signaling Differentially Affects Phase Maintenance and Rhythm Generation in SCN and Extra-SCN Circadian Oscillators

Circadian rhythms in physiology and behavior are coordinated by the brain's dominant circadian pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. Vasoactive intestinal polypeptide (VIP) and its receptor, VPAC2, play important roles in the functioning of the SCN pacemaker. Mice lacking VPAC2 receptors (Vipr2−/−) express disrupted behavioral and metabolic rhythms and show altered SCN neuronal activity and clock gene expression. Within the brain, the SCN is not the only site containing endogenous circadian oscillators, nor is it the only site of VPAC2 receptor expression; both VPAC2 receptors and rhythmic clock gene/protein expression have been noted in the arcuate (Arc) and dorsomedial (DMH) nuclei of the mediobasal hypothalamus, and in the pituitary gland. The functional role of VPAC2 receptors in rhythm generation and maintenance in these tissues is, however, unknown. We used wild type (WT) and Vipr2−/− mice expressing a luciferase reporter (PER2::LUC) to investigate whether circadian rhythms in the clock gene protein PER2 in these extra-SCN tissues were compromised by the absence of the VPAC2 receptor. Vipr2−/− SCN cultures expressed significantly lower amplitude PER2::LUC oscillations than WT SCN. Surprisingly, in Vipr2−/− Arc/ME/PT complex (Arc, median eminence and pars tuberalis), DMH and pituitary, the period, amplitude and rate of damping of rhythms were not significantly different to WT. Intriguingly, while we found WT SCN and Arc/ME/PT tissues to maintain a consistent circadian phase when cultured, the phase of corresponding Vipr2−/− cultures was reset by cull/culture procedure. These data demonstrate that while the main rhythm parameters of extra-SCN circadian oscillations are maintained in Vipr2−/− mice, the ability of these oscillators to resist phase shifts is compromised. These deficiencies may contribute towards the aberrant behavior and metabolism associated with Vipr2−/− animals. Further, our data indicate a link between circadian rhythm strength and the ability of tissues to resist circadian phase resetting