Space Applications Industrial Laser System (SAILS)

A program is underway to develop a YAG laser based materials processing workstation to fly in the cargo bay of the Space Shuttle. This workstation, called Space Applications Industrial Laser System (SAILS), will be capable of cutting and welding steel, aluminum, and Inconel alloys of the type planned for use in constructing the Space Station Freedom. As well as demonstrating the ability of a YAG laser to perform remote (fiber-optic delivered) repair and fabrication operations in space, fundamental data will be collected on these interactions for comparison with terrestrial data and models. The flight system, scheduled to fly in 1996, will be constructed as three modules using standard Get-Away-Special (GAS) canisters. The first module holds the laser head and cooling system, while the second contains a high peak power electrical supply. The third module houses the materials processing workstation and the command and data acquisition subsystems. The laser head and workstation cansisters are linked by a fiber-optic cable to transmit the laser light. The team assembled to carry out this project includes Lumonics Industrial Products (laser), Tennessee Technological University (structural analysis and fabrication), Auburn University Center for Space Power (electrical engineering), University of Waterloo (low-g laser process consulting), and CSTAR/UTSI (data acquisition, control, software, integration, experiment design). This report describes the SAILS program and highlights recent activities undertaken at CSTAR

Effect of P-glycoprotein on flavopiridol sensitivity

Flavopiridol is the first potent inhibitor of cyclin-dependent kinases (CDKs) to enter clinical trials. Little is known about mechanisms of resistance to this agent. In order to determine whether P-glycoprotein (Pgp) might play a role in flavopiridol resistance, we examined flavopiridol sensitivity in a pair of Chinese hamster ovary cell lines differing with respect to level of Pgp expression. The IC 50 s of flavopiridol in parental AuxB1 (lower Pgp) and colchicine-selected CHRC5 (higher Pgp) cells were 90.2 ± 6.6 nM and 117 ± 2.3 nM, respectively (P< 0.01), suggesting that Pgp might have a modest effect on flavopiridol action. Consistent with this hypothesis, pretreatment with either quinidine or verapamil (inhibitors of Pgp-mediated transport) sensitized CHRC5 cells to the antiproliferative effects of flavopiridol. Because of concern that colony forming assays might not accurately reflect cytotoxicity, we also examined flavopiridol-treated cells by trypan blue staining and flow cytometry. These assays confirmed that flavopiridol was less toxic to cells expressing higher levels of Pgp. Further experiments revealed that flavopiridol inhibited the binding of [3H]-azidopine to Pgp in isolated membrane vesicles, but only at high concentrations. Collectively, these results identify flavopiridol as a weak substrate for Pgp. © 2001 Cancer Research Campaign www.bjcancer.co

The homeoprotein DLX3 and tumor suppressor p53 co-regulate cell cycle progression and squamous tumor growth

Epidermal homeostasis depends on the coordinated control of keratinocyte cell cycle. Differentiation and the alteration of this balance can result in neoplastic development. Here we report on a novel DLX3-dependent network that constrains epidermal hyperplasia and squamous tumorigenesis. By integrating genetic and transcriptomic approaches, we demonstrate that DLX3 operates through a p53-regulated network. DLX3 and p53 physically interact on the p21 promoter to enhance p21 expression. Elevating DLX3 in keratinocytes produces a G1-S blockade associated with p53 signature transcriptional profiles. In contrast, DLX3 loss promotes a mitogenic phenotype associated with constitutive activation of ERK. DLX3 expression is lost in human skin cancers and is extinguished during progression of experimentally induced mouse squamous cell carcinoma (SCC). Reinstatement of DLX3 function is sufficient to attenuate the migration of SCC cells, leading to decreased wound closure. Our data establish the DLX3–p53 interplay as a major regulatory axis in epidermal differentiation and suggest that DLX3 is a modulator of skin carcinogenesis

A novel DLX3-PKC integrated signaling network drives keratinocyte differentiation

Epidermal homeostasis relies on a well-defined transcriptional control of keratinocyte proliferation and differentiation, which is critical to prevent skin diseases such as atopic dermatitis, psoriasis or cancer. We have recently shown that the homeobox transcription factor DLX3 and the tumor suppressor p53 co-regulate cell cycle-related signaling and that this mechanism is functionally involved in cutaneous squamous cell carcinoma development. Here we show that DLX3 expression and its downstream signaling depend on protein kinase C alpha (PKC alpha) activity in skin. We found that following 12-O-tetradecanoyl-phorbol-13-acetate (TPA) topical treatment, DLX3 expression is significantly upregulated in the epidermis and keratinocytes from mice overexpressing PKC alpha by transgenic targeting (K5-PKC alpha), resulting in cell cycle block and terminal differentiation. Epidermis lacking DLX3 (DLX3cKO), which is linked to the development of a DLX3-dependent epidermal hyperplasia with hyperkeratosis and dermal leukocyte recruitment, displays enhanced PKC alpha activation, suggesting a feedback regulation of DLX3 and PKC alpha. Of particular significance, transcriptional activation of epidermal barrier, antimicrobial peptide and cytokine genes is significantly increased in DLX3cKO skin and further increased by TPA-dependent PKC activation. Furthermore, when inhibiting PKC activity, we show that epidermal thickness, keratinocyte proliferation and inflammatory cell infiltration are reduced and the PKC-DLX3-dependent gene expression signature is normalized. Independently of PKC, DLX3 expression specifically modulates regulatory networks such as Wnt signaling, phosphatase activity and cell adhesion. Chromatin immunoprecipitation sequencing analysis of primary suprabasal keratinocytes showed binding of DLX3 to the proximal promoter regions of genes associated with cell cycle regulation, and of structural proteins and transcription factors involved in epidermal differentiation. These results indicate that Dlx3 potentially regulates a set of crucial genes necessary during the epidermal differentiation process. Altogether, we demonstrate the existence of a robust DLX3-PKC alpha signaling pathway in keratinocytes that is crucial to epidermal differentiation control and cutaneous homeostasis

Directed Energy Active Illumination for Near-Earth Object Detection

On 15 February 2013, a previously unknown ~20 m asteroid struck Earth near Chelyabinsk, Russia, releasing kinetic energy equivalent to ~570 kt TNT. Detecting objects like the Chelyabinsk impactor that are orbiting near Earth is a difficult task, in part because such objects spend much of their own orbits in the direction of the Sun when viewed from Earth. Efforts aimed at protecting Earth from future impacts will rely heavily on continued discovery. Ground-based optical observatory networks and Earth-orbiting spacecraft with infrared sensors have dramatically increased the pace of discovery. Still, less than 5% of near-Earth objects (NEOs) 100 m/~100 Mt TNT have been identified, and the proportion of known objects decreases rapidly for smaller sizes. Low emissivity of some objects also makes detection by passive sensors difficult. A proposed orbiting laser phased array directed energy system could be used for active illumination of NEOs, enhancing discovery particularly for smaller and lower emissivity objects. Laser fiber amplifiers emit very narrow-band energy, simplifying detection. Results of simulated illumination scenarios are presented based on an orbiting emitter array with specified characteristics. Simulations indicate that return signals from small and low emissivity objects is strong enough to detect. The possibility for both directed and full sky blind surveys is discussed, and the resulting diameter and mass limits for objects in different observational scenarios. The ability to determine both position and speed of detected objects is also discussed

Spatially nonrandom tree mortality and ingrowth maintain equilibrium pattern in an old-growth \u3ci\u3ePseudotsuga–Tsuga\u3c/i\u3e forest

Mortality processes in old-growth forests are generally assumed to be driven by gap-scale disturbance, with only a limited role ascribed to density-dependent mortality, but these assumptions are rarely tested with data sets incorporating repeated measurements. Using a 12-ha spatially explicit plot censused 13 years apart in an approximately 500-year-old Pseudotsuga–Tsuga forest, we demonstrate significant density-dependent mortality and spatially aggregated tree recruitment. However, the combined effect of these strongly nonrandom demographic processes was to maintain tree patterns in a state of dynamic equilibrium. Density-dependent mortality was most pronounced for the dominant latesuccessional species, Tsuga heterophylla. The long-lived, early-seral Pseudotsuga menziesii experienced an annual stem mortality rate of 0.84% and no new recruitment. Late-seral species Tsuga and Abies amabilis had nearly balanced demographic rates of ingrowth and mortality. The 2.34% mortality rate for Taxus brevifolia was higher than expected, notably less than ingrowth, and strongly affected by proximity to Tsuga. Large-diameter Tsuga structured both the regenerating conspecific and heterospecific cohorts with recruitment of Tsuga and Abies unlikely in neighborhoods crowded with large-diameter competitors (P , 0.001). Densitydependent competitive interactions strongly shape forest communities even five centuries after stand initiation, underscoring the dynamic nature of even equilibrial old-growth forests

The impact of global economic crisis and austerity on quality of working life and work- life balance: a capabilities perspective

This paper draws on the capabilities approach as a framework for examining the impact of the global economic crisis and austerity on quality of working life and work-life balance. Our paper focuses on Greece, an extreme case of a country in economic crisis, characterised by a weak institutional basis. We build on the work of Barbara Hobson and colleagues who first applied the capabilities approach to explore work-life balance capabilities. Our study contributes to the development of theory by emphasising the sense of entitlement concept within the capabilities approach and by proposing a modified conceptual framework that encapsulates the link between capabilities, agency, and the sense of entitlement, where the latter acts as a cognitive ‘filter’ that enhances or weakens an individual’s perception of her/his agency to enact on her/his capabilities. Drawing on the accounts of twenty Greek professional and managerial workers, we illustrate how the crisis and austerity measures have eroded working conditions and thus the sense of entitlement, leading to the weakening of our participants’ agency and capabilities to achieve quality of working life and work-life balance

The impact of global economic crisis and austerity on quality of working life and work- life balance: a capabilities perspective

This paper draws on the capabilities approach as a framework for examining the impact of the global economic crisis and austerity on quality of working life and work-life balance. Our paper focuses on Greece, an extreme case of a country in economic crisis, characterised by a weak institutional basis. We build on the work of Barbara Hobson and colleagues who first applied the capabilities approach to explore work-life balance capabilities. Our study contributes to the development of theory by emphasising the sense of entitlement concept within the capabilities approach and by proposing a modified conceptual framework that encapsulates the link between capabilities, agency, and the sense of entitlement, where the latter acts as a cognitive ‘filter’ that enhances or weakens an individual’s perception of her/his agency to enact on her/his capabilities. Drawing on the accounts of twenty Greek professional and managerial workers, we illustrate how the crisis and austerity measures have eroded working conditions and thus the sense of entitlement, leading to the weakening of our participants’ agency and capabilities to achieve quality of working life and work-life balance

Optical Modeling for a Laser Phased-Array Directed Energy System

We present results of optical simulations for a laser phased array directed energy system. The laser array consists of individual optical elements in a square or hexagonal array. In a multi-element array, the far-field beam pattern depends on both mechanical pointing stability and on phase relationships between individual elements. The simulation incorporates realistic pointing and phase errors. Pointing error components include systematic offsets to simulate manufacturing and assembly variations. Pointing also includes time-varying errors that simulate structural vibrations, informed from random vibration analysis of the mechanical design. Phase errors include systematic offsets, and time-varying errors due to both mechanical vibration and temperature variation in the fibers. The optical simulation is used to determine beam pattern and pointing jitter over a range of composite error inputs. Results are also presented for a 1 m aperture array with 10 kW total power, designed as a stand-off system on a dedicated asteroid diversion/capture mission that seeks to evaporate the surface of the target at a distance of beyond 10 km. Phase stability across the array of λ/10 is shown to provide beam control that is sufficient to vaporize the surface of a target at 10 km. The model is also a useful tool for characterizing performance for phase controller design in relation to beam formation and pointing

The impact of global economic crisis and austerity on quality of working life and work- life balance: a capabilities perspective

This paper draws on the capabilities approach as a framework for examining the impact of the global economic crisis and austerity on quality of working life and work-life balance. Our paper focuses on Greece, an extreme case of a country in economic crisis, characterised by a weak institutional basis. We build on the work of Barbara Hobson and colleagues who first applied the capabilities approach to explore work-life balance capabilities. Our study contributes to the development of theory by emphasising the sense of entitlement concept within the capabilities approach and by proposing a modified conceptual framework that encapsulates the link between capabilities, agency, and the sense of entitlement, where the latter acts as a cognitive ‘filter’ that enhances or weakens an individual’s perception of her/his agency to enact on her/his capabilities. Drawing on the accounts of twenty Greek professional and managerial workers, we illustrate how the crisis and austerity measures have eroded working conditions and thus the sense of entitlement, leading to the weakening of our participants’ agency and capabilities to achieve quality of working life and work-life balance