Alpha particle driven Alfv\'enic instabilities in ITER post-disruption plasmas

Fusion-born alpha particles in ITER disruption simulations are investigated as a possible drive of Alfv\'enic instabilities. The ability of these waves to expel runaway electron (RE) seed particles is explored in the pursuit of a passive, inherent RE mitigation scenario. The spatiotemporal evolution of the alpha particle distribution during the disruption is calculated using the linearized Fokker-Planck solver CODION coupled to a fluid disruption simulation. These simulations are done in the limit of no alpha particle transport during the thermal quench, which can be seen as a most pessimistic situation where there is also no RE seed transport. Under these assumptions, the radial anisotropy of the resulting alpha population provides free energy to drive Alfv\'enic modes during the quench phase of the disruption. We use the linear gyrokinetic magnetohydrodynamic code LIGKA to calculate the Alfv\'en spectrum and find that the equilibrium is capable of sustaining a wide range of modes. The self-consistent evolution of the mode amplitudes and the alpha distribution is calculated utilizing the wave-particle interaction tool HAGIS. Intermediate mode number ($n=7-15,~22-26$) Toroidal Alfv\'en Eigenmodes (TAEs) are shown to saturate at an amplitude of up to $\delta B /B \approx 0.1$\% in the spatial regimes crucial for RE seed formation. We find that the mode amplitudes are predicted to be sufficiently large to permit the possibility of significant radial transport of runaway electrons

An ab initio and DFT conformational analysis of unsubstituted and omega-substituted ethyl-benzene: (Ph-CH2-CH2-Z; Z = -H, -F, -NH3+, -CH3)

A series of compounds of Ph-CH2-CH2-Z, with substituents Z = -H, -F, -NH3+-, and -CH3, were subjected to conformational analysis. Conformational potential energy surfaces were generated and their minima were geometrically optimized at three levels of theory. The relative stabilities of the minima correlated with the electron withdrawing nature of the substituents (Z). (C) 2002 Elsevier Science B.V. All rights reserved

Initiative "Kommunales Know-How für Nahost"

INITIATIVE "KOMMUNALES KNOW-HOW FÜR NAHOST" Initiative "Kommunales Know-How für Nahost" / Arslan, Bülent (Rights reserved) ( -

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database. We observed substantial variation in mutation type and frequency by geographical region and race/ethnicity. In addition to known founder mutations, mutations of relatively high frequency were identified in specific racial/ethnic or geographic groups that may reflect founder mutations and which could be used in targeted (panel) first pass genotyping for specific populations. Knowledge of the population-specific mutational spectrum in BRCA1 and BRCA2 could inform efficient strategies for genetic testing and may justify a more broad-based oncogenetic testing in some populations

Evaluation of Sporicidal Disinfectants for the Disinfection of Personal Protective Equipment During Biological Hazards

A fast, effective, and safe disinfection of personal protective equipment (PPE) is vitally important for emergency forces involved in biological hazards. This study aimed to investigate a broad range of disinfectants to improve the established disinfection procedure. We analyzed the efficacy of chlorine-, peracetic acid–, and oxygen-based disinfectants against Bacillus spores on PPE. Therefore, spores of different Bacillus species were exposed to disinfectants on PPE material by using a standardized procedure covering the dried spores with disinfectants and applying mechanical distribution. Efficacy of disinfectants was quantified by determining the reduction factor (log10 levels) and number of viable spores left afterward. The chlorine-based granulate Hypochlorit CA G (2% chlorine) sufficiently inactivated Bacillus spores of risk groups 1 and 2, even with temperatures ranging from −20 to 35°C. Wofasteril® SC super (1.75% peracetic acid) achieved a reliable reduction of risk groups 1 and 2 and even fully virulent Bacillus spores by ≥5 log10 levels on PPE. With this, Hypochlorit-CA G and Wofasteril® SC super proved to be promising alternatives to the previously proven and widely used peracetic acid compound Wofasteril® (2% peracetic acid) for the disinfection of PPE when bacterial spores are known to be the contaminating agent. These results will help to improve the disinfection of PPE during biological hazards by providing new data on promising alternative compounds.Peer Reviewe

CD4⁺ T Cells Are as Protective as CD8⁺ T Cells against <i>Rickettsia typhi</i> Infection by Activating Macrophage Bactericidal Activity

<div><p><i>Rickettsia typhi</i> is an intracellular bacterium that causes endemic typhus, a febrile disease that can be fatal due to complications including pneumonia, hepatitis and meningoencephalitis, the latter being a regular outcome in T and B cell-deficient C57BL/6 RAG1^-/- mice upon <i>Rickettsia typhi</i> infection. Here, we show that CD4⁺ T_H1 cells that are generated in C57BL/6 mice upon <i>R</i>. <i>typhi</i> infection are as protective as cytotoxic CD8⁺ T cells. CD4⁺- as well as CD8⁺-deficient C57BL/6 survived the infection without showing symptoms of disease at any point in time. Moreover, adoptively transferred CD8⁺ and CD4⁺ immune T cells entered the CNS of C57BL/6 RAG1^-/- mice with advanced infection and both eradicated the bacteria. However, immune CD4⁺ T cells protected only approximately 60% of the animals from death. They induced the expression of iNOS in infiltrating macrophages as well as in resident microglia in the CNS which can contribute to bacterial killing but also accelerate pathology. <i>In vitro</i> immune CD4⁺ T cells inhibited bacterial growth in infected macrophages which was in part mediated by the release of IFNγ. Collectively, our data demonstrate that CD4⁺ T cells are as protective as CD8⁺ T cells against <i>R</i>. <i>typhi</i>, provided that CD4⁺ T_H1 effector cells are present in time to support bactericidal activity of phagocytes via the release of IFNγ and other factors. With regard to vaccination against TG <i>Rickettsiae</i>, our findings suggest that the induction of CD4⁺ T_H1 effector cells is sufficient for protection.</p></div

Adoptive transfer of either CD8⁺ or CD4⁺ T cells protects CB17 SCID mice from severe disease and death.

<p>CD4⁺ and CD8⁺ T cells were isolated from naïve BALB/c mice. 1×10⁶ T cells were adoptively transferred into CB17 SCID mice 1 day prior to infection with 1×10⁶ sfu <i>R</i>. <i>typhi</i> or treatment with PBS (Control). Spleen and blood of the animals were analyzed for the presence of T cells on day 7 post infection. The dot plots show example stainings of spleen cells for CD4 and CD8 from a CB17 SCID control mouse, a CD4⁺ T cell recipient (middle) and a CD8⁺ T cell recipient (right). The graphs show the statistical analysis of the spleen (left) and blood (right). The percentage (y-axis) of CD4⁺ and CD8⁺ T cells (x-axis) was determined for control mice (n = 5; white bars), CD4⁺ T cell recipients (n = 5; gray bars) and CD8⁺ T cell recipients (n = 5; black bars). On average CD4⁺ T cell recipients contained 10.1±2.6% CD4⁺ T cells while CD8⁺ T cells were virtually absent (0.9±0.1%). 2.8±0.2% CD8⁺ T cells were detected in CD8⁺ T cells while CD4⁺ T cells were absent (0.6±0.1%). The percentage of T cells in the blood was lower (3.0±0.8% CD4⁺ T cells in CD4⁺ T cell recipient and 1.2±0.3% CD8⁺ T cells in CD8⁺ recipients) (<b>A</b>). Weight change (n = 5 for control animals and n = 6 for T cell recipient groups), clinical score (n = 5 for control animals and n = 6 for T cell recipient groups), survival (n = 11 for each group) and serum GPT levels (n = 3–5 for each group) were assessed (y-axis) at indicated points in time (x-axis). Differences in the weight change between CD4⁺ and CD8⁺ T cell recipients were compared by Mann-Whitney U test at indicated points in time. Statistical analysis of GPT levels was performed by One-way ANOVA (Kruskal Wallis test followed by Dunn´s post) test. Asterisks indicate significant differences compared to day 0 (*<i>p</i><0.05, **<i>p</i><0.01). The survival graph shows combined results from 2 independent experiments. Statistical analysis was performed with Log-rank (Mantel-Cox) test. Asterisks indicate significant differences compared to control animals (**<i>p</i><0.01, ***<i>p</i><0.001) (<b>B</b>).</p

Immune CD4⁺ T cells induce NO release by <i>R</i>. <i>typhi</i>-infected macrophages <i>in vitro</i> and inhibit bacterial growth via IFNγ and TNFα.

<p>1×10⁶ bone-marrow-derived BALB/c macrophages were infected with 5 copies of <i>R</i>. <i>typhi</i> per cell one day prior to the addition of 2×10⁶ purified CD4⁺ T cells from either naïve or immune BALB/c mice (day 7 post infection). IFNγ and TNFα were neutralized by the addition of 10 μg/ml anti-IFNγ and/or anti-TNFα as indicated on the x-axis. Cytokines were quantified in the supernatants 72h after T cell addition by LEGENDplex assay. IFNγ (left, y-axis), TNFα (middle, y-axis), IL-22 (right, y-axis) and IL-2 (below, left) are shown. Other cytokines were not detectable (<b>A</b>). In addition, NO was detected 72h after T cell addition (<b>B</b>). Bacterial content in the cultures (y-axis) was assessed by <i>prsA</i>-specific qPCR 72h after T cell addition (<b>C</b>). 1×10⁶ bone-marrow-derived BALB/c macrophages were treated with recombinant IFNγ (1 U/ml) or TNFα (400 U/ml). NO was quantified in the cell culture supernatants after 72h (<b>D</b>). 1×10⁶ bone-marrow-derived BALB/c macrophages were infected with 5 copies of <i>R</i>. <i>typhi</i> per cell one day prior to the addition of recombinant IFNγ (1 U/ml) or TNFα (400 U/ml). The cytokines were neutralized by simultaneous addition of either anti-TNFα or anti-IFNγ (10 μg/ml each) as indicated on the x-axis. Bacterial content in the cultures (y-axis) was assessed by <i>prsA</i>-specific qPCR 72h after cytokine addition (<b>E</b>). Graphs show the mean±SEM of combined results from 2 independent experiments (n = 4 T cells from each group of mice (A-C) and n = 2 for the treatment with recombinant cytokines (D-E)). Statistical analysis was performed by One-way ANOVA (Kruskal-Wallis test followed by Dunn´s post test). Asterisks indicate significant differences (*<i>p</i><0.05, **<i>p</i><0.01).</p