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The Very High Efficiency Solar Cell (VHESC) program is developing integrated optical system–PV modules for portable applications that operate at greater than 50% efficiency. We are integrating the optical design with the solar cell design, and have entered previously unoccupied design space. Our approach is driven by proven quantitative models for the solar cell design, the optical design, and the integration of these designs. Optical systems efficiency with an optical efficiency of 93% and solar cell device results under ideal dichroic splitting optics summing to 42·7 ± 2·5% are described. Copyright © 2008 John Wiley & Sons, Ltd.

Background Circulating testosterone plays an important role in maintenance and growth of prostate cells. Luteinizing hormone (LH), secreted from the anterior pituitary, signals testicular Leydig cells to secrete testosterone. A genetic variant of the LH-β protein, LH-βV, exists in up to 40% of Caucasians and is more bioactive than the wild-type protein. We hypothesized that genetically determined variation in LH function might affect susceptibility to prostate cancer via altered testosterone secretion. Methods We determined the frequency of the LH-βV polymorphism (two linked polymorphisms: Trp8 Arg and Ile15 Thr) in familial prostate cancer patients (n = 446), in sporadic prostate cancer patients (n = 388), and in population-based controls without prostate cancer (n = 510) to assess the role of this polymorphism in susceptibility to prostate cancer. Results A higher frequency of this variant genotype (LH-βV: Arg8/Thr15) was observed in familial prostate cancer patients (18.6%) than in controls (13.7%), and after taking into account the correlation of the familial cases and adjusting for age and body mass index (BMI), there was a weak positive association between the variant LH-β genotype, and risk of familial prostate cancer (OR = 1.29; 95% CI 0.96–1.75). The sporadic case group was also slightly more likely to have a variant genotype (15.2%) compared to the controls (13.7%), and after adjustment for age and BMI, a similar association with this variant was found (OR = 1.33; 95% CI 0.86–02.07). Surgical cases showed a slightly stronger association for the variant LH-β genotype compared to non-surgical cases, but among the surgical cases there was little variability in risk across nodal status, stage, and tumor grade. Conclusions These data are consistent with the hypothesis that the LH-β variant is a weak risk factor for prostate cancer. Prostate 56: 30–36, 2003. © 2003 Wiley-Liss, Inc.

The RNASEL gene on chromosome 1q25 was recently identified as a candidate gene for hereditary prostate cancer (PC). To confirm these findings, we screened 326 patients from 163 families with familial PC for potential germline mutations, by use of conformation-sensitive gel electrophoresis, followed by direct sequence analysis. A total of six variants were identified, including one intronic and five exonic changes (three missense and two silent alterations). There were no unequivocal pathogenic changes. To further test for potential associations between genes and increased risk for disease, the three missense polymorphisms (Ile97Leu, Arg462Gln, and Glu541Asp) were genotyped in 438 patients with familial PC and in 510 population-based control subjects. Association testing revealed no significant differences between patients and control subjects for either the Leu97 variant (χ 2 trend test=1.42; P =.23) or the Asp541 variant (χ 2 =1.52; P =.22). However, significant differences were detected for the Arg462Gln genotypes (χ 2 =5.20; P =.02; odds ratio [OR] = 0.54; 95% confidence interval [CI] 0.32–0.91) when the genotype Gln/Gln was compared with Arg/Arg. In subset analyses, associations were also observed in the younger group (age at diagnosis ≤64 years) ( P =.0008; OR=0.29; 95% CI=0.13–0.66), in node-negative patients ( P =.01; OR=0.48; 95% CI 0.27–0.84), patients with stage T 1 /T 2 disease ( P =.008; OR=0.39; 95% CI 0.2–0.75), and patients with low-grade disease ( P =.01; OR=0.40; 95% CI 0.20–0.78). To evaluate whether this variant was also associated with sporadic PC, we genotyped an additional 499 patients with sporadic PC. Differences in frequency were not detected between patients with sporadic disease and control subjects. However, the same association was observed between patients with familial disease and patients with sporadic disease for the entire group (χ 2 =4.82; P =.03), as well as in the subset analyses. These results suggest that polymorphic changes within the RNASEL gene may be associated with increased risk of familial but not sporadic PC.

A comprehensive analysis of somatic and germline mutations related to DNA mismatch-repair (MMR) genes can clarify the prevalence and mechanism of inactivation in colorectal carcinoma (CRC). In the present study, 257 unselected patients referred for CRC resection were examined for evidence of defective DNA MMR. In particular, we sought to determine the frequency of hereditary defects in DNA MMR in this cohort of patients. MMR status was assessed by testing of tumors for the presence or absence of hMLH1, hMSH2, and hMSH6 protein expression and for microsatellite instability (MSI). Of the 257 patients, 51 (20%) had evidence of defective MMR, demonstrating high levels of MSI (MSI-H) and an absence of either hMLH1 (n=48) or hMSH2 (n=3). All three patients lacking hMSH2, as well as one patient lacking hMLH1, also demonstrated an absence of hMSH6. DNA sequence analysis of the 51 patients with defective MMR revealed seven germline mutations-four in hMLH1 (two truncating and two missense) and three in hMSH2 (all truncating). A detailed family history was available for 225 of the 257 patients. Of the seven patients with germline mutations, only three had family histories consistent with hereditary nonpolyposis colorectal cancer. Of the remaining patients who had tumors with defective MMR, eight had somatic mutations in hMLH1. In addition, hypermethylation of the hMLH1 gene promoter was present in 37 (88%) of the 42 hMLH1-negative cases available for study and in all MSI-H tumors that showed loss of hMLH1 expression but no detectable hMLH1 mutations. Our results suggest that, although defective DNA MMR occurs in approximately 20% of unselected patients presenting for CRC resection, hereditary CRC due to mutations in the MMR pathway account for only a small proportion of patients. Of the 257 patients, only 5 (1.9%) appear to have unequivocal evidence of hereditary defects in MMR. The epigenetic (nonhereditary) mechanism of hMLH1 promoter hypermethylation appears to be responsible for the majority of the remaining patients whose tumors are characterized by defective DNA MMR.

This paper examines the effects of pressure on the dynamics of prestiffened structures such as the Space Shuttle solid rocket booster and the advanced solid rocket motor. Differences of up to 45% between analytical and test results for the SRB pitch/roll mode frequency are shown to be a result of an extra stiffness term resulting from the applied pressure load. In the past, these effects have been modeled empirically based on test data. In this paper, these pressure stiffness terms are derived analytically for various types of line and area finite elements. These new elements have been implemented as dummy elements in COSMIC NASTRAN and can be easily added to any existing NASTRAN finite element model. The pressure stiffness elements are tested on some simple example problems and are used in existing SRB NASTRAN models to analytically match the quarter-scale SRB pitch/roll test frequencies with differences of less than 5%.

This paper discusses the theory for the dynamic analysis of simple rotationally symmetric structures showing how the problem can be reduced to the analysis of a single segment. The rotational transformation equations are derived and then inverted to obtain the decoupled harmonic equations of motion. Using inter-segment compatibility, the degrees of freedom are reduced to an independent set and the equations of motion are solved. Some special relationsheip between the harmonics and the modal displacements are derived including the relationship between the mode shapes for certain harmonics and the shape of the lateral displacements around the circumference of the structure. Examples including an analysis of the space shuttle main engine fuel turbopump third stage impeller are included.

The Integrated Technology Assessment Center (ITAC) has developed a flexible systems analysis framework to identify long-term technology needs, quantify payoffs for technology investments, and assess the progress of ASTP-sponsored technology programs in the hypersonics area. For this, ITAC has assembled an experienced team representing a broad sector of the aerospace community and developed a systematic assessment process complete with supporting tools. Concepts for transportation systems are selected based on relevance to the ASTP and integrated concept models (ICM) of these concepts are developed. Key technologies of interest are identified and projections are made of their characteristics with respect to their impacts on key aspects of the specific concepts of interest. Both the models and technology projections are then fed into the ITAC's probabilistic systems analysis framework in ModelCenter. This framework permits rapid sensitivity analysis, single point design assessment, and a full probabilistic assessment of each concept with respect to both embedded and enhancing technologies. Probabilistic outputs are weighed against metrics of interest to ASTP using a multivariate decision making process to provide inputs for technology prioritization within the ASTP. ITAC program is currently finishing the assessment of a two-stage-to-orbit (TSTO), rocket-based combined cycle (RBCC) concept and a TSTO turbine-based combined cycle (TBCC) concept developed by the team with inputs from NASA. A baseline all rocket TSTO concept is also being developed for comparison. Boeing has recently submitted a performance model for their Flexible Aerospace System Solution for Tomorrow (FASST) concept and the ISAT program will provide inputs for a single-stage-to-orbit (SSTO) TBCC based concept in the near-term. Both of these latter concepts will be analyzed within the ITAC framework over the summer. This paper provides a status update of the ITAC program.

Early implementation of structural dynamics finite element analyses for calculation of design loads is considered common design practice for high volume manufacturing industries such as automotive and aeronautical industries. However with the rarity of rocket engine development programs starts, these tools are relatively new to the design of rocket engines. In the NASA MC-1 engine program, the focus was to reduce the cost-to-weight ratio. The techniques for structural dynamics analysis practices, were tailored in this program to meet both production and structural design goals. Perturbation of rocket engine design parameters resulted in a number of MC-1 load cycles necessary to characterize the impact due to mass and stiffness changes. Evolution of loads and load extraction methodologies, parametric considerations and a discussion of load path sensitivities are important during the design and integration of a new engine system. During the final stages of development, it is important to verify the results of an engine system model to determine the validity of the results. During the final stages of the MC-1 program, hot-fire test results were obtained and compared to the structural design loads calculated by the engine system model. These comparisons are presented in this paper.

Microsatellite instability (MSI) is a genomic alteration observed in 15-30% of colorectal cancer (CRC). Two MSI phenotypes have been defined for CRC: MSI-H is characterized by MSI ator =30% of the examined loci and MSI-L by MSI at 1-30% of the loci. An absence of MSI at any examined loci has been defined as a microsatellite stable (MSS) phenotype. Current data suggest the majority of MSI tumors are the result of defective DNA mismatch repair (MMR). In this study, we have determined the alpha(1)-antitrypsin deficiency carrier (alpha(1)ATD-ht) status of 161 CRC patients whose MSI phenotype and protein expression states had previously been determined. Cases were selected to enrich a larger number of MSI-H cases. Among 51 CRC patients with MSI-H tumors, the alpha(1)ATD-ht rate was 21.6%; among 110 patients with MSI-L/MSS tumors, the rate was 9.1% (MSI-H vs MSI-L/MSS, P = 0.02); and among the 191 population-based controls the alpha(1)ATD-ht rate was 9.4% (MSI-H vs controls, P = 0.02). The estimated relative risk of having MSI-H CRC among alpha(1)ATD-ht was 3.1 after adjusting for age, gender, and smoking history. The risk of having MSI-H CRC among current and past smokers was 6.6 and 2.7, respectively. Patients who were alpha(1)ATD-ht and smoked had a 20-fold increased risk of developing an MSI-H CRC compared to nonsmokers who were homozygous normal at the alpha(1)ATD locus. Our findings suggest an etiologic link between alpha(1)ATD alleles and development of CRC with defective MMR, and a synergistic effect between smoking and alpha(1)ATD allele in the development of MSI-H CRC.

Early implementation of structural dynamics finite element analyses for calculation of design loads is considered common design practice for high volume manufacturing industries such as automotive and aeronautical industries. However, with the rarity of rocket engine development programs starts, these tools are relatively new to the design of rocket engines. In the new Fastrac engine program, the focus has been to reduce the cost to weight ratio; current structural dynamics analysis practices were tailored in order to meet both production and structural design goals. Perturbation of rocket engine design parameters resulted in a number of Fastrac load cycles necessary to characterize the impact due to mass and stiffness changes. Evolution of loads and load extraction methodologies, parametric considerations and a discussion of load path sensitivities are discussed.

We evaluated the usefulness of fluorescence in situ hybridization (FISH) using different-colored commercial RB1 and 13qter DNA probes to identify RB1 deletions in interphase nuclei of bone marrow from 24 patients with agnogenic myeloid metaplasia (AMM), 20 patients with multiple myeloma (MM), 21 patients with other hematologic malignancies, and 25 normal bone marrow transplant (BMT) donors. Based on the 25 normal BMT donors, the upper boundary for the normal percentage of nuclei with one RB1 signal was 6.5%. Based on eight specimens known to have a deletion of 13q14 by cytogenetic studies, the lower limit of abnormal for the percentage of nuclei with one RB1 signal was 12.5%. More than 12.5% of nuclei had a single RB1 signal in 7/24 (29%) patients with AMM and 3/20 (15%) patients with MM. None of the 21 patients with hematologic malignancies other than AMM or MM had more than 12.5% nuclei with loss of RB1. The results of this study suggest that FISH with RB1 probes is useful to detect loss of RB1 in interphase nuclei from patients with hematologic disorders who have chromosome abnormalities involving 13q14. Thus, FISH with probes for RB1 is efficacious to investigate the pathogenesis of RB1 in malignant neoplasms and is a useful adjunct to conventional cytogenetic studies in clinical practice when abnormalities of 13q14 are involved.

We have developed a three-color cytoplasmic immunoglobulin (clg) and fluorescence in situ hybridization (FISH) technique to detect plasma cell chromosomal aneuploidy in patients with multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), smoldering multiple myeloma (SMM), and amyloidosis (AL). Immunofluorescent-labeled antibodies to detect light chain expression and six directly labeled α-satellite chromosome specific enumeration probes (CEP) were used simultaneously to detect aneuploidy of the plasma cells. The six probes were specific for chromosomes 7, 9, 11, 15, 18, and X. The technique was tested in 12 consecutive patient samples (5 MM, 2 MGUS, 3 SMM, and 2 AL). Based on the a-satellite signals, we found trisomic clones for CEP 7 (4 of 12), CEP 11 (4 of 12), CEP X (1 of 12), CEP 9 (8 of 12), CEP 15 (7 of 12), and CEP 18 (5 of 12). Trisomic clones of at least one of the six chromosomes were present in 9 of 12 patients. We believe that this technique efficiently identifies monotypic plasma cells and permits simultaneous analysis of numeric chromosome anomalies by FISH in emerging neoplastic cells. We are in the process of applying this technique to a series of about 100 newly diagnosed monoclonal gammopathy patients.

Three children with deletions of the terminal portion of the long arm of chromosome 2 [del (2) (q37)] are described and their clinical findings compared to published cases of 2q terminal deletions. Common clinical findings include development delay, macrocephaly, frontal bossing, depressed nasal bridge and cardiac anomaly. Hypotonia and repetitive behavior are also seen during different times of development. The facial characteristics of children with 2q terminal deletions are not uniform, but development delay is a constant finding. Chromosomal analysis of such children using high resolution banding may uncover the diagnosis of a small chromosomal deletion.

We investigated the usefulness of fluorescent in situ hybridization with different-colored major breakpoint cluster region (Mbcr) and Abelson oncogene (abl) probes in clinical practice. In standard Ph chromosomes with a Mbcr breakpoint, these probes produced a fusion of Mbcr and abl signals that was visible in interphase and metaphase cells. The normal range for apparent Mbcr/abl fusion signals in interphase nuclei was established in bone marrow from 25 normal controls. We tested the probes on 35 bone marrow specimens from five normal subjects and 29 patients with various kinds of Ph chromosomes and chronic myelogenous leukemia or acute lymphocytic leukemia. This method produced Mbcr/abl fusion signals in patients with a standard Ph chromosome, simple or complex variants of Ph chromosomes, and "Ph-negative chronic myelogenous leukemia." In metaphase cells of patients with acute lymphocytic leukemia, this method established Ph chromosomes with minor bcr (mbcr) breakpoints. Fluorescent in situ hybridization is a relatively inexpensive and rapid method. When this method is used in conjunction with conventional chromosome analysis, the cytogeneticist can combine the power of complete karyotype studies and the resolution of molecular techniques for patients suspected of having a Ph chromosome.

This paper discusses the effect of pressure on the dynamics of pre-stiffened structures such as the Advanced Solid Rocket Motor (ASRM). Previous work in which the stiffness terms resulting from constant pressure were derived has been extended to enable modeling of nonconstant pressure applied over nonenclosed volumes. These conditions will result in nonsymmetric terms in the global stiffness matrix which will not cancel out. Three new pressure stiffness elements incorporating these nonsymmetric terms have been implemented as dummy elements in COSMIC NASTRAN and have been tested on various simple examples as well as an existing ASRM NASTRAN finite element model. The results indicate that for all load cases of practical interest to the ASRM program, the nonsymmetric terms have very little effect on the dynamic characteristics. In addition, the pressure stiffness elements developed in the previous work which assumed constant pressure gave virtually the same results as the new elements even for problems in which the pressures are not constant. The original elements appear to work well as long as the pressure gradient across any individual element is no larger than about 0.75 psi/inch. The new elements are therefore most useful for determining the conditions under which the original pressure stiffness elements can be used.

We describe a method for use of fluorescent-labeled whole chromosome-specific paint probes on GTL-banded metaphases to utilize the combined potential of these techniques for defining chromosome abnormalities. The efficacy of this method was tested on 6 cases involving different chromosome abnormalities and various tissues, including blood, amniotic fluid, skin fibroblasts, and bone marrow.

Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating β-catenin/TCF signalling