Constraints on the implementation of concurrent engineering with suppliers in civil and defence design communities: differentiating design ethos

A thesis submitted to the Luton Business School, University of Luton, in fulfilment ofthe requirements for the degree of Doctor of PhilosophySuccessful Concurrent Engineering (CE) with suppliers requires a pre-disposition on the part of the prime company and the supplier to work in this manner. This thesis explores the impact of design ethos on the implementation of Supplier-inLoop (SIL) CE between an Original Equipment Manufacturer (OEM) and a first tier supplier. Design ethos for the purpose of this thesis is described as 'a characteristic manner or approach to constraints on SIL displayed by personnel involved in the design of new products'. This research employs a mixed-method to understand SIL constraints across industry sectors. A design ethos framework is developed and a military design community is characterised in terms of anomalies to the existing literature. These anomalies are then tested through a questionnaire and then interpreted in terms of the design ethos framework. The results of this comparison show that some characteristics are common to both the civil and military design communities and some are not. A case is made that design ethos, in the context of SIL, is primarily determined by: suppliers' aptitude, skill level and contracts; problems with data I information exchange mechanisms; existing processes, relationships and management support; supplier history; technological view of the product; external influences on the process; existing design milestones; visibility of supplier capability; and, continuity of service in terms of skill and data security. The research concludes that the implementation of SIL is directly impacted by design ethos, and that for SIL to be a success in the military sector design ethos must be managed in line with business objectives. The contribution to knowledge that this thesis provides is the insight it offers into the human issues associated with implementing concurrent engineering with external suppliers, and the identification of sector-specific issues as well as those which will benefit from cross sectoral learning. It is of value to military and civil OEMs for purpose of change management, also to their suppliers in understanding the different needs of military and civil customers when working in a concurrent engmeenng manner

Three-Body Capture of Irregular Satellites: Application to Jupiter

We investigate a new theory of the origin of the irregular satellites of the giant planets: capture of one member of a ~100-km binary asteroid after tidal disruption. The energy loss from disruption is sufficient for capture, but it cannot deliver the bodies directly to the observed orbits of the irregular satellites. Instead, the long-lived capture orbits subsequently evolve inward due to interactions with a tenuous circumplanetary gas disk. We focus on the capture by Jupiter, which, due to its large mass, provides the most stringent test of our model. We investigate the possible fates of disrupted bodies, the differences between prograde and retrograde captures, and the effects of Callisto on captured objects. We make an impulse approximation and discuss how it allows us to generalize capture results from equal-mass binaries to binaries with arbitrary mass ratios. We find that at Jupiter, binaries offer an increase of a factor of ~10 in the capture rate of 100-km objects as compared to single bodies, for objects separated by tens of radii that approach the planet on relatively low-energy trajectories. These bodies are at risk of collision with Callisto, but may be preserved by gas drag if their pericenters are raised quickly enough. We conclude that our mechanism is as capable of producing large irregular satellites as previous suggestions, and it avoids several problems faced by alternative models.Comment: 39 pages, 12 figures, 1 table, submitted to Icaru

Three-Body Capture of Jupiter's Irregular Satellites and Resonant History of the Galilean Satellites

We examine the capture of small, irregular satellites, which, with their distant, eccentric, and inclined paths, must have originated in heliocentric orbits. We investigate a new theory: capture of one member of a pair of ∼100-km asteroids after tidal disruption. The energy loss from disruption is sufficient for capture, but it cannot deliver the bodies directly to the currently observed orbits. Instead, the long-lived capture orbits must evolve inward after capture, perhaps due to interactions with a tenuous circumplanetary gas disk. We find that at Jupiter, binaries offer an increase of a factor of ∼10 in the capture rate of 100-km objects as compared to single bodies, for objects separated by tens of radii that approach the planet on relatively low-energy trajectories. These bodies are at risk of collision with Callisto, but may be preserved by gas drag if their pericenters are raised quickly enough. We conclude that our mechanism is as capable of producing large irregular satellites as previous suggestions, and it avoids several problems faced by alternative models. To investigate possible source populations for these captured satellites, we simulated escaping asteroids from Jupiter's Trojan region and the outer main belt, calculating the Jacobi constant during close approaches and comparing with three-body capture statistics. We found that Trojans' high approach speeds make them unlikely source bodies, but asteroids from the outer main belt, especially those interior to Jupiter's 4:3 resonance, approach with low speeds that favor capture. Unlike irregular satellites, regular satellites formed with their planets. Gravitational resonances are important for these bodies, and we study the most famous of them. Io, Europa, and Ganymede are in the Laplace resonance, meaning that they have orbital periods in the ratio of 1:2:4. We focused our work on Io and Europa's orbital lock and modeled passage through the 2:1 resonances. We discovered cases where damping from satellite tides led to stable equilibria prior to capturing into the resonances. The mean-motion ratio at which this occurs matches that of Io and Europa. We conclude that the moons never captured into resonance, and that their resonant angles librate because of long-range resonant forcing

Observations of Extreme ICME Ram Pressure Compressing Mercury's Dayside Magnetosphere to the Surface

Mercury's magnetosphere is known to be affected by enhanced ram pressures and magnetic fields inside interplanetary coronal mass ejections (ICMEs). Here we report detailed observations of an ICME compressing Mercury's dayside magnetosphere to the surface. A fast CME launched from the Sun on November 29 2013 impacted first MESSENGER, which was orbiting Mercury, on November 30 and later STEREO-A near 1 AU on December 1. Following the ICME impact, MESSENGER remained in the solar wind as the spacecraft traveled inwards and northwards towards Mercury's surface until it reached and passed its closest approach to the planet (at 371 km altitude) without crossing into the magnetosphere. The magnetospheric crossing finally occurred 1 minute before reaching the planet's nightside at 400 km altitude and 84$^\circ$N latitude, indicating the lack of dayside magnetosphere on this orbit. In addition, the peak magnetic field measured by MESSENGER at this time was 40% above the values measured in the orbits just prior to and after the ICME, a consequence of the magnetospheric compression. Using both a proxy method at Mercury and measurements at STEREO-A, we show that the extremely high ram pressure associated with this ICME was more than high enough to collapse Mercury's weak magnetosphere. As a consequence, the ICME plasma likely interacted with Mercury's surface, evidenced by enhanced sodium ions in the exosphere. The collapse of Mercury's dayside magnetosphere has important implications for the habitability of close-in exoplanets around M dwarf stars, as such events may significantly contribute to planetary atmospheric loss in these systems

Assessing cellular efficacy of bromodomain inhibitors using fluorescence recovery after photobleaching

BACKGROUND: Acetylation of lysine residues in histone tails plays an important role in the regulation of gene transcription. Bromdomains are the readers of acetylated histone marks, and, consequently, bromodomain-containing proteins have a variety of chromatin-related functions. Moreover, they are increasingly being recognised as important mediators of a wide range of diseases. The first potent and selective bromodomain inhibitors are beginning to be described, but the diverse or unknown functions of bromodomain-containing proteins present challenges to systematically demonstrating cellular efficacy and selectivity for these inhibitors. Here we assess the viability of fluorescence recovery after photobleaching (FRAP) assays as a target agnostic method for the direct visualisation of an on-target effect of bromodomain inhibitors in living cells. RESULTS: Mutation of a conserved asparagine crucial for binding to acetylated lysines in the bromodomains of BRD3, BRD4 and TRIM24 all resulted in reduction of FRAP recovery times, indicating loss of or significantly reduced binding to acetylated chromatin, as did the addition of known inhibitors. Significant differences between wild type and bromodomain mutants for ATAD2, BAZ2A, BRD1, BRD7, GCN5L2, SMARCA2 and ZMYND11 required the addition of the histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) to amplify the binding contribution of the bromodomain. Under these conditions, known inhibitors decreased FRAP recovery times back to mutant control levels. Mutation of the bromodomain did not alter FRAP recovery times for full-length CREBBP, even in the presence of SAHA, indicating that other domains are primarily responsible for anchoring CREBBP to chromatin. However, FRAP assays with multimerised CREBBP bromodomains resulted in a good assay to assess the efficacy of bromodomain inhibitors to this target. The bromodomain and extraterminal protein inhibitor PFI-1 was inactive against other bromodomain targets, demonstrating the specificity of the method. CONCLUSIONS: Viable FRAP assays were established for 11 representative bromodomain-containing proteins that broadly cover the bromodomain phylogenetic tree. Addition of SAHA can overcome weak binding to chromatin, and the use of tandem bromodomain constructs can eliminate masking effects of other chromatin binding domains. Together, these results demonstrate that FRAP assays offer a potentially pan-bromodomain method for generating cell-based assays, allowing the testing of compounds with respect to cell permeability, on-target efficacy and selectivity

Sexual function in 16- to 21-year-olds in Britain

Purpose: Concern about young people's sexuality is focused on the need to prevent harmful outcomes such as sexually transmitted infections and unplanned pregnancy. Although the benefit of a broader perspective is recognized, data on other aspects of sexuality, particularly sexual function, are scant. We sought to address this gap by measuring the population prevalence of sexual function problems, help seeking, and avoidance of sex in young people. Methods: A cross-sectional stratified probability sample survey (Natsal-3) of 15,162 women and men in Britain (response rate: 57.7%), using computer-assisted self-interviews. Data come from 1875 (71.9%) sexually active, and 517 sexually inactive (18.7%), participants aged 16–21 years. Measures were single items from a validated measure of sexual function (the Natsal-SF). Results: Among sexually active 16- to 21-year-old participants, 9.1% of men and 13.4% of women reported a distressing sexual problem lasting 3 months or more in the last year. Most common among men was reaching a climax too quickly (4.5%), and among women was difficulty in reaching climax (6.3%). Just over a third (35.5%) of men and 42.3% of women reporting a problem had sought help, but rarely from professional sources. Among those who had not had sex in the last year, just >10% of young men and women said they had avoided sex because of sexual difficulties. Conclusions: Distressing sexual function problems are reported by a sizeable minority of sexually active young people. Education is required, and counseling should be available, to prevent lack of knowledge, anxiety, and shame progressing into lifelong sexual difficulties

Tracing oncogene-driven remodelling of the intestinal stem cell niche.

Interactions between tumour cells and the surrounding microenvironment contribute to tumour progression, metastasis and recurrence1-3. Although mosaic analyses in Drosophila have advanced our understanding of such interactions4,5, it has been difficult to engineer parallel approaches in vertebrates. Here we present an oncogene-associated, multicolour reporter mouse model-the Red2Onco system-that allows differential tracing of mutant and wild-type cells in the same tissue. By applying this system to the small intestine, we show that oncogene-expressing mutant crypts alter the cellular organization of neighbouring wild-type crypts, thereby driving accelerated clonal drift. Crypts that express oncogenic KRAS or PI3K secrete BMP ligands that suppress local stem cell activity, while changes in PDGFRloCD81+ stromal cells induced by crypts with oncogenic PI3K alter the WNT signalling environment. Together, these results show how oncogene-driven paracrine remodelling creates a niche environment that is detrimental to the maintenance of wild-type tissue, promoting field transformation dominated by oncogenic clones.Royal Societ

MESSENGER observations of induced magnetic fields in Mercury's core

Orbital data from the Magnetometer on the MErcury Surface, Space ENvironment, GEochemistry, and Ranging (MESSENGER) spacecraft allow investigation of magnetic fields induced at the top of Mercury's core by time‐varying magnetospheric fields. We used 15 Mercury years of observations of the magnetopause position as well as the magnetic field inside the magnetosphere to establish the presence and magnitude of an annual induction signal. Our results indicate an annual change in the internal axial dipole term, g10, of 7.5 to 9.5 nT. For negligible mantle conductivity, the average annual induction signal provides an estimate of Mercury's core radius to within ±90 km, independent of geodetic results. Larger induction signals during extreme events are expected but are challenging to identify because of reconnection‐driven erosion. Our results indicate that the magnetopause reaches the dayside planetary surface 1.5–4% of the time

Modular model for Mercury's magnetospheric magnetic field confined within the average observed magnetopause

Accurate knowledge of Mercury's magnetospheric magnetic field is required to understand the sources of the planet's internal field. We present the first model of Mercury's magnetospheric magnetic field confined within a magnetopause shape derived from Magnetometer observations by the MErcury Surface, Space ENvironment, GEochemistry, and Ranging spacecraft. The field of internal origin is approximated by a dipole of magnitude 190 nT RM 3, where RM is Mercury's radius, offset northward by 479 km along the spin axis. External field sources include currents flowing on the magnetopause boundary and in the cross‐tail current sheet. The cross‐tail current is described by a disk‐shaped current near the planet and a sheet current at larger (≳ 5 RM ) antisunward distances. The tail currents are constrained by minimizing the root‐mean‐square (RMS) residual between the model and the magnetic field observed within the magnetosphere. The magnetopause current contributions are derived by shielding the field of each module external to the magnetopause by minimizing the RMS normal component of the magnetic field at the magnetopause. The new model yields improvements over the previously developed paraboloid model in regions that are close to the magnetopause and the nightside magnetic equatorial plane. Magnetic field residuals remain that are distributed systematically over large areas and vary monotonically with magnetic activity. Further advances in empirical descriptions of Mercury's magnetospheric external field will need to account for the dependence of the tail and magnetopause currents on magnetic activity and additional sources within the magnetosphere associated with Birkeland currents and plasma distributions near the dayside magnetopause

Bird and bat predation services in tropical forests and agroforestry landscapes

Understanding distribution patterns and multitrophic interactions is critical for managing batâ and birdâ mediated ecosystem services such as the suppression of pest and nonâ pest arthropods. Despite the ecological and economic importance of bats and birds in tropical forests, agroforestry systems, and agricultural systems mixed with natural forest, a systematic review of their impact is still missing. A growing number of bird and bat exclosure experiments has improved our knowledge allowing new conclusions regarding their roles in food webs and associated ecosystem services. Here, we review the distribution patterns of insectivorous birds and bats, their local and landscape drivers, and their effects on trophic cascades in tropical ecosystems. We report that for birds but not bats community composition and relative importance of functional groups changes conspicuously from forests to habitats including both agricultural areas and forests, here termed â forestâ agriâ habitats, with reduced representation of insectivores in the latter. In contrast to previous theory regarding trophic cascade strength, we find that birds and bats reduce the density and biomass of arthropods in the tropics with effect sizes similar to those in temperate and boreal communities. The relative importance of birds versus bats in regulating pest abundances varies with season, geography and management. Birds and bats may even suppress tropical arthropod outbreaks, although positive effects on plant growth are not always reported. As both bats and birds are major agents of pest suppression, a better understanding of the local and landscape factors driving the variability of their impact is needed.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134094/1/brv12211_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134094/2/brv12211.pd