Identifikation neuer Kandidatengene fuer suizidales Verhalten durch Microarrayversuche

Nach Angaben des statistischen Bundesamtes starben in Deutschland in den vergangenen Jahren durchschnittlich 11.000 Menschen durch Suizid. Suizidales Verhalten ist sehr komplex und wird sowohl durch Umwelteinflüsse als auch durch genetische Faktoren beeinflusst. Es wird dabei ein polygener Erbgang mit multiplen Suszeptibilitätsgenen angenommen, die jeweils nur einen kleinen Einfluss haben. Insgesamt ist bisher aber nur wenig zu den beteiligten Genen und neurobiologischen Mechanismen bekannt. Ziel der vorliegenden Arbeit war die Identifikation neuer Kandidatengene für suizidales Verhalten durch Microarrayversuche. Im Rahmen dieser Fragestellung wurde die Expression von mehr als 23.000 Transkripten in post mortem Hirngewebe aus dem orbitofrontalen Cortex von 11 Suizidenten und 10 Kontrollpersonen bestimmt. Bei einem Signifikanzniveau von α = 0,01 waren insgesamt 124 Gene in der Suizidgruppe differentiell exprimiert. Die Validierung der Ergebnisse mit Hilfe der quantitativen Real-Time-PCR konnte die Richtung der Expressionsänderung für 15 von 16 untersuchten Genen bestätigen. Die anschließende Klassifizierung der identifizierten Gene nach ihrer biologischen Funktion zeigte, daß verschiedene Gene Ontology Kategorien signifikant überrepräsentiert waren. Insgesamt geben die gefundenen Expressionsunterschiede erste Hinweise auf eine mögliche Bedeutung dieser Gene und biologischen Funktionskreise für die Entstehung suizidales Verhaltens

SiC Based Beam Monitoring System for Particle Rates from kHz to GHz

The extremely low dark current of silicon carbide (SiC) detectors, even after high-fluence irradiation, was utilized to develop a beam monitoring system for a wide range of particle rates, i.e., from the kHz to the GHz regime. The system is completely built from off-the-shelve components and is focused on compactness and simple deployment. Beam tests using a 50 um thick SiC detector reveal, that for low fluences, single particles can be detected and counted. For higher fluences, beam properties were extracted from beam cross sections using a silicon strip detector. Overall accurate results were achieved up to a particle rate of 109 particles per second

The role of hyperfine coupling in magnetic and quadrupolar ordering of Pr3Pd20Si6

We study the ternary clathrate Pr3Pd20Si6 in specific heat and AC-susceptibility measurements on a high-quality single crystal, distinguishing antiferromagnetic (AFM) and antiferroquadrupolar (AFQ) ordering on two sublattices of inequivalent Pr sites. The specific heat shows the direct involvement of nuclear spin degrees of freedom in the AFM ordering, which is well supported by our calculation of the hyperfine level scheme without adjustable parameters. Pr3Pd20Si6 is therefore one of the rare materials where the nuclear moments are involved in the formation of the magnetic ground state.Comment: 5 pages, 5 figure

Performance of neutron-irradiated 4H-Silicon Carbide diodes subjected to Alpha radiation

The unique electrical and material properties of 4H-silicon-carbide (4H-SiC) make it a promising candidate material for high rate particle detectors. In contrast to the ubiquitously used silicon (Si), 4H-SiC offers a higher carrier saturation velocity and larger breakdown voltage, enabling a high intrinsic time resolution and mitigating pile-up effects. Additionally, as radiation hardness requirements grow more demanding, wide-bandgap materials such as 4H-SiC could offer better performance. In this work, the detector performance of 50 micron thick 4H-SiC p-in-n planar pad sensors was investigated at room temperature, using an 241Am alpha source at reverse biases of up to 1100 V. Samples subjected to neutron irradiation with fluences of up to 1e16/cm^2 were included in the study in order to quantify the radiation hardness properties of 4H-SiC. The obtained results are compared to previously performed UV-TCT studies. Samples exhibit a drop in charge collection efficiency (CCE) with increasing irradiation fluence, partially compensated at high reverse bias voltages far above full depletion voltage. A plateau of the collected charges is observed in accordance with the depletion of the volume the alpha particles penetrate for an unirradiated reference detector. For the neutron-irradiated samples, such a plateau only becomes apparent at higher reverse bias. For the highest investigated fluence, CCE behaves almost linearly with increasing reverse bias. Compared to UV-TCT measurements, the reverse bias required to deplete a sensitive volume covering full energy deposition is lower, due to the small penetration depth of the alpha particles. At the highest reverse bias, the measured CCE values agree well with earlier UV-TCT studies, with discrepancies between 1% and 5%.Comment: 10 pages (8 without references), 6 figures, 1 table, to be published in the Proceedings Section of Journal of Instrumentation (JINST) as a proceeding of iWoRiD202

Magnetic properties of a spin-1/2 quadrumer chain

We study a novel S=1/2 cluster chain Hamiltonian which has recently been proposed in the context of the charge ordered low-temperature phase of alpha'-NaV2O5. We perform a detailed investigation of this model within a large range of parameters using perturbation theory and Lanczos diagonalization. Using model-specific local conservation laws and parameter-dependent mappings to various effective low-energy Hamiltonians we uncover a rich phase diagram and several regimes of gapful spin-excitations. We find that the overall features of recent neutron scattering data on alpha'-NaV2O5 can be fitted within this model, however using a set of parameters which seems unlikely.Comment: 9 pages REVTeX, 11 PostScript figures included using psfig.sty; final version to appear in Phys. Rev. B: New appendix, modified Figs. 1 & 10 and other small change

Randomized controlled phase 2 trial of hydroxychloroquine in childhood interstitial lung disease

Background No results of controlled trials are available for any of the few treatments offered to children with interstitial lung diseases (chILD). We evaluated hydroxychloroquine (HCQ) in a phase 2, prospective, multicentre, 1:1-randomized, double-blind, placebo-controlled, parallel-group/crossover trial. HCQ (START arm) or placebo were given for 4 weeks. Then all subjects received HCQ for another 4 weeks. In the STOP arm subjects already taking HCQ were randomized to 12 weeks of HCQ or placebo (= withdrawal of HCQ). Then all subjects stopped treatment and were observed for another 12 weeks. Results 26 subjects were included in the START arm, 9 in the STOP arm, of these four subjects participated in both arms. The primary endpoint, presence or absence of a response to treatment, assessed as oxygenation (calculated from a change in transcutaneous O 2 -saturation of ≥ 5%, respiratory rate ≥ 20% or level of respiratory support), did not differ between placebo and HCQ groups. Secondary endpoints including change of O 2 -saturation ≥ 3%, health related quality of life, pulmonary function and 6-min-walk-test distance, were not different between groups. Finally combining all placebo and all HCQ treatment periods did not identify significant treatment effects. Overall effect sizes were small. HCQ was well tolerated, adverse events were not different between placebo and HCQ. Conclusions Acknowledging important shortcomings of the study, including a small study population, the treatment duration, lack of outcomes like lung function testing below age of 6 years, the small effect size of HCQ treatment observed requires careful reassessments of prescriptions in everyday practice (EudraCT-Nr.: 2013-003714-40, www.clinicaltrialsregister.eu , registered 02.07.2013)

Randomized controlled phase 2 trial of hydroxychloroquine in childhood interstitial lung disease

Abstract Background No results of controlled trials are available for any of the few treatments offered to children with interstitial lung diseases (chILD). We evaluated hydroxychloroquine (HCQ) in a phase 2, prospective, multicentre, 1:1-randomized, double-blind, placebo-controlled, parallel-group/crossover trial. HCQ (START arm) or placebo were given for 4 weeks. Then all subjects received HCQ for another 4 weeks. In the STOP arm subjects already taking HCQ were randomized to 12 weeks of HCQ or placebo (= withdrawal of HCQ). Then all subjects stopped treatment and were observed for another 12 weeks. Results 26 subjects were included in the START arm, 9 in the STOP arm, of these four subjects participated in both arms. The primary endpoint, presence or absence of a response to treatment, assessed as oxygenation (calculated from a change in transcutaneous O2-saturation of ≥ 5%, respiratory rate ≥ 20% or level of respiratory support), did not differ between placebo and HCQ groups. Secondary endpoints including change of O2-saturation ≥ 3%, health related quality of life, pulmonary function and 6-min-walk-test distance, were not different between groups. Finally combining all placebo and all HCQ treatment periods did not identify significant treatment effects. Overall effect sizes were small. HCQ was well tolerated, adverse events were not different between placebo and HCQ. Conclusions Acknowledging important shortcomings of the study, including a small study population, the treatment duration, lack of outcomes like lung function testing below age of 6 years, the small effect size of HCQ treatment observed requires careful reassessments of prescriptions in everyday practice (EudraCT-Nr.: 2013-003714-40, www.clinicaltrialsregister.eu , registered 02.07.2013). Registration The study was registered on 2 July 2013 (Eudra-CT Number: 2013-003714-40), whereas the approval by BfArM was received 24.11.2014, followed by the approval by the lead EC of the University Hospital Munich on 20.01.2015. At clinicaltrials.gov the trial was additionally registered on November 8, 2015 (NCT02615938)

From antiferromagnetic and hidden order to Pauli paramagnetism in UM2Si2 compounds with 5f electron duality

Using inelastic X-ray scattering beyond the dipole limit and hard X-ray photoelectron spectroscopy we establish the dual nature of the U 5f electrons in UM2Si2 (M = Pd, Ni, Ru, Fe), regardless of their degree of delocalization. We have observed that the compounds have in common a local atomic-like state that is well described by the U 5f(2) configuration with the Gamma((1))(1) and Gamma(2) quasi-doublet symmetry. The amount of the U 5f(3) configuration, however, varies considerably across the UM2Si2 series, indicating an increase of U 5f itineracy in going from M = Pd to Ni to Ru and to the Fe compound. The identified electronic states explain the formation of the very large ordered magnetic moments in UPd2Si2 and UNi2Si2, the availability of orbital degrees of freedom needed for the hidden order in URu2Si2 to occur, as well as the appearance of Pauli paramagnetism in UFe2Si2. A unified and systematic picture of the UM2Si2 compounds may now be drawn, thereby providing suggestions for additional experiments to induce hidden order and/or superconductivity in U compounds with the tetragonal body-centered ThCr2Si2 structure