Global sensitivity analysis of detailed chemical kinetic schemes for DME oxidation in premixed flames

Detailed chemical kinetic investigations on dimethylether oxidation in one-dimensional premixed flat flames were performed. Local and global sensitivities of the reaction rate constants within selected chemical kinetic schemes were studied using maximum flame temperature, and peak methane and formaldehyde concentrations as predictive target quantities. The global sensitivity analysis was based on the application of high dimensional model representations using quasi-random sampling. First- and second-order sensitivity indices of important reaction steps were determined for fuel rich (Φ = 1.49) and fuel lean (Φ = 0.67) conditions. Differences in the importance ranking for key reactions were found to exist between the selected schemes, highlighting the influence of differences in the key rate constants. Whilst the peak flame temperature was predicted with fairly low uncertainty by both schemes, significant uncertainties were identified in the prediction of the target minor species. Key reaction rates requiring better quantification in order to improve the prediction of methane and formaldehyde concentrations are identified

Two specific mutations are prevalent causes of recessive retinitis pigmentosa in North American patients of Jewish ancestry.

PURPOSE: Retinitis pigmentosa is a Mendelian disease with a very elevated genetic heterogeneity. Most mutations are responsible for less than 1% of cases, making molecular diagnosis a multigene screening procedure. In this study, we assessed whether direct testing of specific alleles could be a valuable screening approach in cases characterized by prevalent founder mutations. METHODS: We screened 275 North American patients with recessive/isolate retinitis pigmentosa for two mutations: an Alu insertion in the MAK gene and the p.Lys42Glu missense in the DHDDS gene. All patients were unrelated; 35 reported Jewish ancestry and the remainder reported mixed ethnicity. RESULTS: We identified the MAK and DHDDS mutations homozygously in only 2.1% and 0.8%, respectively, of patients of mixed ethnicity, but in 25.7% and 8.6%, respectively, of cases reporting Jewish ancestry. Haplotype analyses revealed that inheritance of the MAK mutation was attributable to a founder effect. CONCLUSION: In contrast to most mutations associated with retinitis pigmentosa-which are, in general, extremely rare-the two alleles investigated here cause disease in approximately one-third of North American patients reporting Jewish ancestry. Therefore, their screening constitutes an alternative procedure to large-scale tests for patients belonging to this ethnic group, especially in time-sensitive situations.Genet Med 17 4, 285-290

Detecting autozygosity through runs of homozygosity: A comparison of three autozygosity detection algorithms

<p>Abstract</p> <p>Background</p> <p>A central aim for studying runs of homozygosity (ROHs) in genome-wide SNP data is to detect the effects of autozygosity (stretches of the two homologous chromosomes within the same individual that are identical by descent) on phenotypes. However, it is unknown which current ROH detection program, and which set of parameters within a given program, is optimal for differentiating ROHs that are truly autozygous from ROHs that are homozygous at the marker level but vary at unmeasured variants between the markers.</p> <p>Method</p> <p>We simulated 120 Mb of sequence data in order to know the true state of autozygosity. We then extracted common variants from this sequence to mimic the properties of SNP platforms and performed ROH analyses using three popular ROH detection programs, PLINK, GERMLINE, and BEAGLE. We varied detection thresholds for each program (e.g., prior probabilities, lengths of ROHs) to understand their effects on detecting known autozygosity.</p> <p>Results</p> <p>Within the optimal thresholds for each program, PLINK outperformed GERMLINE and BEAGLE in detecting autozygosity from distant common ancestors. PLINK's sliding window algorithm worked best when using SNP data pruned for linkage disequilibrium (LD).</p> <p>Conclusion</p> <p>Our results provide both general and specific recommendations for maximizing autozygosity detection in genome-wide SNP data, and should apply equally well to research on whole-genome autozygosity burden or to research on whether specific autozygous regions are predictive using association mapping methods.</p

Characterization of megahertz X ray laser beams by multishot desorption imprints in PMMA

Proper diagnostics of intense free electron laser FEL X ray pulses is indisputably important for experimental data analysis as well as for the protection of beamline optical elements. New challenges for beam diagnostic methods are introduced by modern FEL facilities capable of delivering powerful pulses at megahertz MHz repetition rates. In this paper, we report the first characterization of a defocused MHz 13.5 nm beam generated by the free electron laser in Hamburg FLASH using the method of multi pulse desorption imprints in poly methyl methacrylate PMMA . The beam fluence profile is reconstructed in a novel and highly accurate way that takes into account the nonlinear response of material removal to total dose delivered by multiple pulses. The algorithm is applied to experimental data of single shot ablation imprints and multi shot desorption imprints at both low 10 Hz and high 1 MHz repetition rates. Reconstructed response functions show a great agreement with the theoretical desorption response function mode