Feasibility study of an Integrated Program for Aerospace vehicle Design (IPAD) Volume 7: IPAD benefits and impact

The potential benefits, impact and spinoff of IPAD technology are described. The benefits are projected from a flowtime and labor cost analysis of the design process and a study of the flowtime and labor cost savings being experienced with existing integrated systems. Benefits in terms of designer productivity, company effectiveness, and IPAD as a national resource are developed. A description is given of the potential impact of information handling as an IPAD technology, upon task and organization structure and people who use IPAD. Spinoff of IPAD technology to nonaerospace industries is discussed. The results of a personal survey made of aerospace, nonaerospace, government and university sources are given

Feasibility study of an Integrated Program for Aerospace vehicle Design (IPAD). Volume 1B: Concise review

Reports on the design process, support of the design process, IPAD System design catalog of IPAD technical program elements, IPAD System development and operation, and IPAD benefits and impact are concisely reviewed. The approach used to define the design is described. Major activities performed during the product development cycle are identified. The computer system requirements necessary to support the design process are given as computational requirements of the host system, technical program elements and system features. The IPAD computer system design is presented as concepts, a functional description and an organizational diagram of its major components. The cost and schedules and a three phase plan for IPAD implementation are presented. The benefits and impact of IPAD technology are discussed

Feasibility study of an Integrated Program for Aerospace vehicle Design (IPAD). Volume 3: Support of the design process

The user requirements for computer support of the IPAD design process are identified. The user-system interface, language, equipment, and computational requirements are considered

Area deprivation across the life course and physical capability in mid-life: findings from the 1946 British Birth Cohort

Physical capability in later life is influenced by factors occurring across the life course, yet exposures to area conditions have only been examined cross-sectionally. Data from the National Survey of Health and Development, a longitudinal study of a 1946 British birth cohort, were used to estimate associations of area deprivation (defined as percentage of employed people working in partly skilled or unskilled occupations) at ages 4, 26, and 53 years (residential addresses linked to census data in 1950, 1972, and 1999) with 3 measures of physical capability at age 53 years: grip strength, standing balance, and chair-rise time. Cross-classified multilevel models with individuals nested within areas at the 3 ages showed that models assessing a single time point underestimate total area contributions to physical capability. For balance and chair-rise performance, associations with area deprivation in midlife were robust to adjustment for individual socioeconomic position and prior area deprivation (mean change for a 1-standard-deviation increase: balance, −7.4% (95% confidence interval (CI): −12.8, −2.8); chair rise, 2.1% (95% CI: −0.1, 4.3)). In addition, area deprivation in childhood was related to balance after adjustment for childhood socioeconomic position (−5.1%, 95% CI: −8.7, −1.6). Interventions aimed at reducing midlife disparities in physical capability should target the socioeconomic environment of individuals—for standing balance, as early as childhood

Feasibility study of an Integrated Program for Aerospace vehicle Design (IPAD). Volume 1A: Summary

IPAD was defined as a total system oriented to the product design process. This total system was designed to recognize the product design process, individuals and their design process tasks, and the computer-based IPAD System to aid product design. Principal elements of the IPAD System include the host computer and its interactive system software, new executive and data management software, and an open-ended IPAD library of technical programs to match the intended product design process. The basic goal of the IPAD total system is to increase the productivity of the product design organization. Increases in individual productivity were feasible through automation and computer support of routine information handling. Such proven automation can directly decrease cost and flowtime in the product design process

Dark states in the light-harvesting complex 2 revealed by two-dimensional electronic spectroscopy

Energy transfer and trapping in the light harvesting antennae of purple photosynthetic bacteria is an ultrafast process, which occurs with a quantum efficiency close to unity. However the mechanisms behind this process have not yet been fully understood. Recently it was proposed that low-lying energy dark states, such as charge transfer states and polaron pairs, play an important role in the dynamics and directionality of energy transfer. However, it is difficult to directly detect those states because of their small transition dipole moment and overlap with the B850/B870 exciton bands. Here we present a new experimental approach, which combines the selectivity of two-dimensional electronic spectroscopy with the availability of genetically modified light harvesting complexes, to reveal the presence of those dark states in both the genetically modified and the wild-type light harvesting 2 complexes of Rhodopseudomonas palustris. We suggest that Nature has used the unavoidable charge transfer processes that occur when LH pigments are concentrated to enhance and direct the flow of energy

Functional Conservation of the Glide/Gcm Regulatory Network Controlling Glia, Hemocyte, and Tendon Cell Differentiation in Drosophila.

High-throughput screens allow us to understand how transcription factors trigger developmental processes, including cell specification. A major challenge is identification of their binding sites because feedback loops and homeostatic interactions may mask the direct impact of those factors in transcriptome analyses. Moreover, this approach dissects the downstream signaling cascades and facilitates identification of conserved transcriptional programs. Here we show the results and the validation of a DNA adenine methyltransferase identification (DamID) genome-wide screen that identifies the direct targets of Glide/Gcm, a potent transcription factor that controls glia, hemocyte, and tendon cell differentiation in Drosophila. The screen identifies many genes that had not been previously associated with Glide/Gcm and highlights three major signaling pathways interacting with Glide/Gcm: Notch, Hedgehog, and JAK/STAT, which all involve feedback loops. Furthermore, the screen identifies effector molecules that are necessary for cell-cell interactions during late developmental processes and/or in ontogeny. Typically, immunoglobulin (Ig) domain-containing proteins control cell adhesion and axonal navigation. This shows that early and transiently expressed fate determinants not only control other transcription factors that, in turn, implement a specific developmental program but also directly affect late developmental events and cell function. Finally, while the mammalian genome contains two orthologous Gcm genes, their function has been demonstrated in vertebrate-specific tissues, placenta, and parathyroid glands, begging questions on the evolutionary conservation of the Gcm cascade in higher organisms. Here we provide the first evidence for the conservation of Gcm direct targets in humans. In sum, this work uncovers novel aspects of cell specification and sets the basis for further understanding of the role of conserved Gcm gene regulatory cascades.We thank the DHSB and the Bloomington Stock Center for reagents and flies as well as J. Veenstra (INCIA UMR 5287 CNRS, France) for the gift of the Anti-DH31 antibody and B. Altenhein (U Mainz, Germany) for fly strains. We thank K. Jamet for initial bioinformatics analyses. We thank C. Diebold, C. Delaporte, and IGBMC facilities for technical assistance. We thank the members of the lab for valuable input and comments on the manuscript. This work was supported by INSERM, CNRS, UDS, Hôpital de Strasbourg, ARC, INCA and ANR grants. A. Popkova and P. Cattenoz were funded by the FRM and by the ANR, respectively. A. Popkova also benefitted from a short Development traveling fellowship to visit the laboratory of A. Brand in Cambridge (UK). The IGBMC was also supported by a French state fund through the ANR labex. T.D.S and A.H.B were funded by Wellcome Trust Programme Grants 068055 and 092545 to A.H.B. A.H.B acknowledges core funding to the Gurdon Institute from the Wellcome Trust (092096) and CRUK (C6946/A14492).This is the final version of the article. It was first available from the American Genetics Society via http://dx.doi.org/10.1534/genetics.115.18215

The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons.

BACKGROUND: While developmental processes such as axon pathfinding and synapse formation have been characterized in detail, comparatively less is known of the intrinsic developmental mechanisms that regulate transcription of ion channel genes in embryonic neurons. Early decisions, including motoneuron axon targeting, are orchestrated by a cohort of transcription factors that act together in a combinatorial manner. These transcription factors include Even-skipped (Eve), islet and Lim3. The perdurance of these factors in late embryonic neurons is, however, indicative that they might also regulate additional aspects of neuron development, including the acquisition of electrical properties. RESULTS: To test the hypothesis that a combinatorial code transcription factor is also able to influence the acquisition of electrical properties in embryonic neurons we utilized the molecular genetics of Drosophila to manipulate the expression of Eve in identified motoneurons. We show that increasing expression of this transcription factor, in two Eve-positive motoneurons (aCC and RP2), is indeed sufficient to affect the electrical properties of these neurons in early first instar larvae. Specifically, we observed a decrease in both the fast K+ conductance (IKfast) and amplitude of quantal cholinergic synaptic input. We used charybdotoxin to pharmacologically separate the individual components of IKfast to show that increased Eve specifically down regulates the Slowpoke (a BK Ca2+-gated potassium channel), but not Shal, component of this current. Identification of target genes for Eve, using DNA adenine methyltransferase identification, revealed strong binding sites in slowpoke and nAcRalpha-96Aa (a nicotinic acetylcholine receptor subunit). Verification using real-time PCR shows that pan-neuronal expression of eve is sufficient to repress transcripts for both slo and nAcRalpha-96Aa. CONCLUSION: Taken together, our findings demonstrate, for the first time, that Eve is sufficient to regulate both voltage- and ligand-gated currents in motoneurons, extending its known repertoire of action beyond its already characterized role in axon guidance. Our data are also consistent with a common developmental program that utilizes a defined set of transcription factors to determine both morphological and functional neuronal properties

In-beam internal conversion electron spectroscopy with the SPICE detector

The SPectrometer for Internal Conversion Electrons (SPICE) has been commissioned for use in conjunction with the TIGRESS $\gamma$-ray spectrometer at TRIUMF's ISAC-II facility. SPICE features a permanent rare-earth magnetic lens to collect and direct internal conversion electrons emitted from nuclear reactions to a thick, highly segmented, lithium-drifted silicon detector. This arrangement, combined with TIGRESS, enables in-beam $\gamma$-ray and internal conversion electron spectroscopy to be performed with stable and radioactive ion beams. Technical aspects of the device, capabilities, and initial performance are presented