Structural-Thermal-Optical-Performance (STOP) Model Development and Analysis of a Field-widened Michelson Interferometer

An integrated Structural-Thermal-Optical-Performance (STOP) model was developed for a field-widened Michelson interferometer which is being built and tested for the High Spectral Resolution Lidar (HSRL) project at NASA Langley Research Center (LaRC). The performance of the interferometer is highly sensitive to thermal expansion, changes in refractive index with temperature, temperature gradients, and deformation due to mounting stresses. Hand calculations can only predict system performance for uniform temperature changes, under the assumption that coefficient of thermal expansion (CTE) mismatch effects are negligible. An integrated STOP model was developed to investigate the effects of design modifications on the performance of the interferometer in detail, including CTE mismatch, and other three- dimensional effects. The model will be used to improve the design for a future spaceflight version of the interferometer. The STOP model was developed using the Comet SimApp'TM' Authoring Workspace which performs automated integration between Pro-Engineer, Thermal Desktop, MSC Nastran'TM', SigFit'TM', Code V'TM', and MATLAB. This is the first flight project for which LaRC has utilized Comet, and it allows a larger trade space to be studied in a shorter time than would be possible in a traditional STOP analysis. This paper describes the development of the STOP model, presents a comparison of STOP results for simple cases with hand calculations, and presents results of the correlation effort to bench-top testing of the interferometer. A trade study conducted with the STOP model which demonstrates a few simple design changes that can improve the performance seen in the lab is also presented

Identification and functional characterization of a novel mutation in the NKX2-1 gene: Comparison with the data in the literature

Background: NKX2-1 mutations have been described in several patients with primary congenital hypothyroidism, respiratory distress, and benign hereditary chorea, which are classical manifestations of the brain-thyroid-lung syndrome (BTLS). Methods: The NKX2-1 gene was sequenced in the members of a Brazilian family with clinical features of BTLS, and a novel monoallelic mutation was identified in the affected patients. We introduced the mutation in an expression vector for the functional characterization by transfection experiments using both thyroidal and lung-specific promoters. Results: The mutation is a deletion of a cytosine at position 834 (ref. sequence NM-003317) (c.493delC) that causes a frameshift with formation of an abnormal protein from amino acid 165 and a premature stop at position 196. The last amino acid of the nuclear localization signal, the whole homeodomain, and the carboxy-terminus of NKX2-1 are all missing in the mutant protein, which has a premature stop codon at position 196 (p.Arg165Glyfs*32). The p.Arg165Glyfs*32 mutant does not bind DNA, and it is unable to transactivate the thyroglobulin (Tg) and the surfactant protein-C (SP-C) promoters. Interestingly, a dose-dependent dominant negative effect of the p.Arg165Glyfs*32 was demonstrated only on the Tg promoter, but not on the SP-C promoter. This effect was also noticed when the mutation was tested in presence of PAX8 or cofactors that synergize with NKX2-1 (P300 and TAZ). The functional effect was also compared with the data present in the literature and demonstrated that, so far, it is very difficult to establish a specific correlation among NKX2-1 mutations, their functional consequence, and the clinical phenotype of affected patients, thus suggesting that the detailed mechanisms of transcriptional regulation still remain unclear. Conclusions: We describe a novel NKX2-1 mutation and demonstrate that haploinsufficiency may not be the only explanation for BTLS. Our results indicate that NKX2-1 activity is also finely regulated in a tissue-specific manner, and additional studies are required to better understand the complexities of genotype-phenotype correlations in the NKX2-1 deficiency syndrome. © Copyright 2013, Mary Ann Liebert, Inc. 2013