Spatial restriction of alpha4 integrin phosphorylation regulates lamellipodial stability and alpha4beta1-dependent cell migration.

Integrins coordinate spatial signaling events essential for cell polarity and directed migration. Such signals from alpha4 integrins regulate cell migration in development and in leukocyte trafficking. Here, we report that efficient alpha4-mediated migration requires spatial control of alpha4 phosphorylation by protein kinase A, and hence localized inhibition of binding of the signaling adaptor, paxillin, to the integrin. In migrating cells, phosphorylated alpha4 accumulated along the leading edge. Blocking alpha4 phosphorylation by mutagenesis or by inhibition of protein kinase A drastically reduced alpha4-dependent migration and lamellipodial stability. alpha4 phosphorylation blocks paxillin binding in vitro; we now find that paxillin and phospho-alpha4 were in distinct clusters at the leading edge of migrating cells, whereas unphosphorylated alpha4 and paxillin colocalized along the lateral edges of those cells. Furthermore, enforced paxillin association with alpha4 inhibits migration and reduced lamellipodial stability. These results show that topographically specific integrin phosphorylation can control cell migration and polarization by spatial segregation of adaptor protein binding

The Habitat Demonstration Unit Project Overview

This paper will describe an overview of the National Aeronautics and Space Administration (NASA) led multi-center Habitat Demonstration Unit (HDU) Project. The HDU project is a "technology-pull" project that integrates technologies and innovations from numerous NASA centers. This project will be used to investigate and validate surface architectures, operations concepts, and requirements definition of various habitation concepts. The first habitation configuration this project will build and test is the Pressurized Excursion Module (PEM). This habitat configuration - the PEM - is based on the Constellation Architecture Scenario 12.1 concept of a vertically oriented habitat module. The HDU project will be tested as part of the 2010 Desert Research and Technologies Simulations (D-RATS) test objectives. The purpose of this project is to develop, integrate, test, and evaluate a habitat configuration in the context of the mission architectures and surface operation concepts. A multi-center approach will be leveraged to build, integrate, and test the PEM through a shared collaborative effort of multiple NASA centers. The HDU project is part of the strategic plan from the Exploration Systems Mission Directorate (ESMD) Directorate Integration Office (DIO) and the Lunar Surface Systems Project Office (LSSPO) to test surface elements in a surface analog environment. The 2010 analog field test will include two Lunar Electric Rovers (LER) and the PEM among other surface demonstration elements. This paper will describe the overall objectives, its various habitat configurations, strategic plan, and technology integration as it pertains to the 2010 and 2011 field analog tests. To accomplish the development of the PEM from conception in June 2009 to rollout for operations in July 2010, the HDU project team is using a set of design standards to define the interfaces between the various systems of PEM and to the payloads, such as the Geology Lab, that those systems will support. Scheduled activities such as early fit-checks and the utilization of a habitat avionics test bed prior to equipment installation into PEM are planned to facilitate the integration process

The Habitat Demonstration Unit System Integration

The Lunar Surface System Habitat Demonstration Unit (HDU) will require a project team to integrate a variety of contributions from National Aeronautics and Space Administration (NASA) centers and potential outside collaborators and poses a challenge in integrating these disparate efforts into a cohesive architecture. To accomplish the development of the first version of the HDU, the Pressurized Excursion Module (PEM), from conception in June 2009 to rollout for operations in July 2010, the HDU project team is using several strategies to mitigate risks and bring the separate efforts together. First, a set of design standards is being developed to define the interfaces between the various systems of PEM and to the payloads, such as the Geology Laboratory, that those systems will support. Scheduled activities such as early fit-checks and the utilization of a habitat avionics test bed prior to equipment installation into HDU PEM are planned to facilitate the integration process. A coordinated effort to establish simplified Computer Aided Design (CAD) standards and the utilization of a modeling and simulation systems will aid in design and integration concept development. Finally, decision processes on the shell development including the assembly sequence and the transportation have been fleshed out early on HDU design to maximize the efficiency of both integration and field operations

Radial Internal Material Handling System (RIMS) for Circular Habitat Volumes

On planetary surfaces, pressurized human habitable volumes will require a means to carry equipment around within the volume of the habitat, regardless of the partial gravity (Earth, Moon, Mars, etc.). On the NASA Habitat Demonstration Unit (HDU), a vertical cylindrical volume, it was determined that a variety of heavy items would need to be carried back and forth from deployed locations to the General Maintenance Work Station (GMWS) when in need of repair, and other equipment may need to be carried inside for repairs, such as rover parts and other external equipment. The vertical cylindrical volume of the HDU lent itself to a circular overhead track and hoist system that allows lifting of heavy objects from anywhere in the habitat to any other point in the habitat interior. In addition, the system is able to hand-off lifted items to other material handling systems through the side hatches, such as through an airlock. The overhead system consists of two concentric circle tracks that have a movable beam between them. The beam has a hoist carriage that can move back and forth on the beam. Therefore, the entire system acts like a bridge crane curved around to meet itself in a circle. The novelty of the system is in its configuration, and how it interfaces with the volume of the HDU habitat. Similar to how a bridge crane allows coverage for an entire rectangular volume, the RIMS system covers a circular volume. The RIMS system is the first generation of what may be applied to future planetary surface vertical cylinder habitats on the Moon or on Mars

A Visual Literacy Strategy - Why not?

The paper asserts that the National Curriculum subjects of 'art and design' and 'design and technology' have a fundamental connection that has not been fully recognised or exploited in primary schools. The two subjects help children to develop important skills of aesthetic awareness, discrimination and critical thinking and that they could do this through a common rationale and approach to the development of visual literacy. The paper goes on to review the term 'visual literacy'. A new term - 'visual field' is offered as a way of connecting objects and artefacts of both broadly functional and broadly aesthetic natures. Pedagogic frameworks in current use by primary teachers intended to promote critical discussion are analysed with reference to the visual field. It is concluded that each framework has a different emphasis yet each is concerned with and therefore connected by the visual field. The paper concludes that a coherent strategy to ensure all children have the opportunity to become visually literate should be developed

Successful use of axonal transport for drug delivery by synthetic molecular vehicles

We report the use of axonal transport to achieve intraneural drug delivery. We constructed a novel tripartite complex of an axonal transport facilitator conjugated to a linker molecule bearing up to a hundred reversibly attached drug molecules. The complex efficiently enters nerve terminals after intramuscular or intradermal administration and travels within axonal processes to neuron cell bodies. The tripartite agent provided 100-fold amplification of saturable neural uptake events, delivering multiple drug molecules per complex. _In vivo_, analgesic drug delivery to systemic and to non-targeted neural tissues was greatly reduced compared to existing routes of administration, thus exemplifying the possibility of specific nerve root targeting and effectively increasing the potency of the candidate drug gabapentin 300-fold relative to oral administration