1,563 research outputs found
Aerospace applications of high temperature superconductivity
Space application of high temperature superconducting (HTS) materials may occur before most terrestrial applications because of the passive cooling possibilities in space and because of the economic feasibility of introducing an expensive new technology which has a significant system benefit in space. NASA Lewis Research Center has an ongoing program to develop space technology capitalizing on the potential benefit of HTS materials. The applications being pursued include space communications, power and propulsion systems, and magnetic bearings. In addition, NASA Lewis is pursuing materials research to improve the performance of HTS materials for space applications
Determining the Functional Significance of Mismatch Repair Gene Missense Variants Using Biochemical and Cellular Assays
With the discovery that the hereditary cancer susceptibility disease Lynch syndrome (LS) is caused by deleterious germline mutations in the DNA mismatch repair (MMR) genes nearly 20 years ago, genetic testing can now be used to diagnose this disorder in patients. A definitive diagnosis of LS can direct how clinicians manage the disease as well as prevent future cancers for the patient and their families. A challenge emerges, however, when a germline missense variant is identified in a MMR gene in a suspected LS patient. The significance of a single amino acid change in these large repair proteins is not immediately obvious resulting in them being designated variants of uncertain significance (VUS). One important strategy for resolving this uncertainty is to determine whether the variant results in a non-functional protein. The ability to reconstitute the MMR reaction in vitro has provided an important experimental tool for studying the functional consequences of VUS. However, beyond this repair assay, a number of other experimental methods have been developed that allow us to test the effect of a VUS on discrete biochemical steps or other aspects of MMR function. Here, we describe some of these assays along with the challenges of using such assays to determine the functional consequences of MMR VUS which, in turn, can provide valuable insight into their clinical significance. With increased gene sequencing in patients, the number of identified VUS has expanded dramatically exacerbating this problem for clinicians. However, basic science research laboratories around the world continue to expand our knowledge of the overall MMR molecular mechanism providing new opportunities to understand the functional significance, and therefore pathogenic significance, of VUS
High temperature superconducting thin film microwave circuits: Fabrication, characterization, and applications
Epitaxial YBa2Cu3O7 films were grown on several microwave substrates. Surface resistance and penetration depth measurements were performed to determine the quality of these films. Here the properties of these films on key microwave substrates are described. The fabrication and characterization of a microwave ring resonator circuit to determine transmission line losses are presented. Lower losses than those observed in gold resonator circuits were observed at temperatures lower than critical transition temperature. Based on these results, potential applications of microwave superconducting circuits such as filters, resonators, oscillators, phase shifters, and antenna elements in space communication systems are identified
Lynch Syndrome-associated Mutations in MSH2 Alter DNA Repair and Checkpoint Response Functions In Vivo
The DNA mismatch repair (MMR) pathway is essential in maintaining genomic stability through its role in DNA repair and the checkpoint response. Loss of DNA MMR underlies the hereditary cancer disease Lynch Syndrome (LS). Germline mutations in MSH2 account for approximately 40% of LS patients and of these, 18% are missense variants. One important clinical challenge has been discriminating between missense variants that are pathogenic and those that are not. Current analysis of missense mutations in MSH2 is performed using a combination of clinical, biochemical, and functional data; however, suitable cell culture models to test the various functions of the DNA MMR proteins are lacking. Here, we have generated human cell lines stably expressing a subset of MSH2 missense mutants and tested their effect on DNA repair and checkpoint response functions. We have expanded on previous biochemical and functional analyses performed in non-human systems to further understand defects conferred by this subset of single amino acid alterations. The functional characterization of MSH2 missense mutants combined with clinical and biochemical data is essential for appropriate patient management and genetic counseling decisions. ©2010 Wiley-Liss, Inc
Millimeter wave transmission studies of YBa2Cu3O7-delta thin films in the 26.5 to 40.0 GHz frequency range
Millimeter wave transmission measurements through YBa2Cu3O(7-delta) thin films on MgO, ZrO2 and LaAlO3 substrates, are reported. The films (approx. 1 micron) were deposited by sequential evaporation and laser ablation techniques. Transition temperatures T sub c, ranging from 89.7 K for the Laser Ablated film on LaAlO3 to approximately 72 K for the sequentially evaporated film on MgO, were obtained. The values of the real and imaginary parts of the complex conductivity, sigma 1 and sigma 2, are obtained from the transmission data, assuming a two fluid model. The BCS approach is used to calculate values for an effective energy gap from the obtained values of sigma sub 1. A range of gap values from 2 DELTA o/K sub B T sub c = 4.19 to 4.35 was obtained. The magnetic penetration depth is evaluated from the deduced values of sigma 2. These results are discussed together with the frequency dependence of the normalized transmission amplitude, P/P sub c, below and above T sub c
Evolution of a new testis-specific functional promoter within the highly conserved MAP2K7 gene of the mouse
Map2k7(synonymMkk7) is a conserved regulatory kinase gene and a central componentof the JNK signaling cascade with key functions during cellular differentiation. It showscomplex transcription patterns, and different transcript isoforms are known in the mouse(Mus musculus). We have previously identified a newly evolved testis-specific transcript fortheMap2k7gene in the subspeciesM. m. domesticus. Here, we identify the new promoterthat drives this transcript andfind that it codes for an open reading frame (ORF) of 50 aminoacids. The new promoter was gained in the stem lineage of closely related mouse speciesbut was secondarily lost in the subspeciesM. m. musculusandM. m. castaneus. A singlemutation can be correlated with its transcriptional activity inM. m. domesticus, and cellculture assays demonstrate the capability of this mutation to drive expression. A mouseknockout line in which the promoter region of the new transcript is deleted reveals afunctional contribution of the newly evolved promoter to sperm motility and the spermatidtranscriptome. Our data show that a new functional transcript (and possibly protein) canevolve within an otherwise highly conserved gene, supporting the notion of regulatorychanges contributing to the emergence of evolutionary novelties
Polarizable Force Fields for CO<sub>2</sub> and CH<sub>4</sub> Adsorption in M-MOF-74
(Graph Presented) The family of M-MOF-74, with M = Co, Cr, Cu, Fe, Mg, Mn, Ni, Ti, V, and Zn, provides opportunities for numerous energy related gas separation applications. The pore structure of M-MOF-74 exhibits a high internal surface area and an exceptionally large adsorption capacity. The chemical environment of the adsorbate molecule in M-MOF-74 can be tuned by exchanging the metal ion incorporated in the structure. To optimize materials for a given separation process, insights into how the choice of the metal ion affects the interaction strength with adsorbate molecules and how to model these interactions are essential. Here, we quantitatively highlight the importance of polarization by comparing the proposed polarizable force field to orbital interaction energies from DFT calculations. Adsorption isotherms and heats of adsorption are computed for CO2, CH4, and their mixtures in M-MOF-74 with all 10 metal ions. The results are compared to experimental data, and to previous simulation results using nonpolarizable force fields derived from quantum mechanics. To the best of our knowledge, the developed polarizable force field is the only one so far trying to cover such a large set of possible metal ions. For the majority of metal ions, our simulations are in good agreement with experiments, demonstrating the effectiveness of our polarizable potential and the transferability of the adopted approach.</p
- …