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A principle aim of synthetic biology is the design of new biological parts that can be applied to replace or augment natural components in biological systems to produce entirely original functions. A major challenge in this field is the design of ‘switchable’ protein-protein interaction (PPI) domains that could be used to bring together other proteins in a controllable fashion. One approach is the design of components from first principles, or de novo. Coiled coils (CCs) are a protein structural motif that are well adapted to de novo design approaches given the available and well understood sequence-to-structure relationships. Taking inspiration from natural systems, our approach to produce novel switchable PPI domains is through the post-translational modification of CC components. To this end, here we incorporate phosphorylation motifs into de novo designed heterotetrameric CC assemblies and demonstrate their phospho-switching behaviours in vitro. This system elicits rapid and reversible switching between tetramer and monomer state in response to enzyme-catalysed phosphorylation and dephosphorylation. Next, we describe the application of this system in vivo, with the aim of producing a switchable PPI domain that can function orthogonally to host cell signalling processes. The designed switchable CCs function in E. coli cells. However, toxicity caused by the expression of the kinase ‘switch’ prevents the system functioning as anticipated in vivo. To overcome this, we reversed the switching mechanism by directly incorporating phosphoserine during protein expression in vivo, and expressing a phosphatase to trigger the switch between states. Promising preliminary results have been obtained. Such minimal switches have great potential to deliver dynamic functions to designed proteins, including the control of synthetic signalling networks, amongst other important synthetic biology applications. This project has also delivered an entirely new CC design for an ant

Megan Riley McGilchrist sees the Vietnam War and the cultural upheaval it represents as a watershed event in understanding how the western novel treats the theme of landscape. She constructs her analysis through the writings of Wallace Stegner and the western novels of Cormac McCarthy, the former retaining a belief in the innate goodness of the land and the latter rejecting the benevolence of the natural world. McGilchrist argues that, as the fulfillment of the frontier ethos, the Vietnam War-absent in Stegner but present in McCarthy-changed life in the mythimbued West. For McGilchrist, elements of the mythic West, both abhorrent and appealing, include boundless land, strong men, passive women, colonization of Indigenous peoples, hope, and grandeur.

The mission of the Uzbek Modelling and Simulation Working Group (MSWG) and this initiative is to develop a comprehensive, integrated, state-off-the-art M&S and Advanced Distributed Learning capability for the Uzbek Armed Forces that will significantly improve operational readiness and technical capabilities. The MSWG is lead by the Ministry of Defense (MOD) with representative from the MOD, Military Academy and other parts of the Armed Forces, U.S. Office of the Assistant Secretary of Defense International Security Policy) (OASD (ISP)) Eurasia, the U.S. Defense Attache Office (USDAO) in Tashkent, and the U.S. Modeling and Simulation Information and Analysis Center (MSIAC). The MSIAC has brought the power and capabilities of the US ET to assist with this effort in Uzbekistan. The specific characteristics of this initiative are shown below: 1. Fight-year (plus) multi-phased program; 2. National M&S Center and 18 interconnected distributed facilities - Military Colleges, Sergeants Schools, Operational Commands and other Ministries involved with Civil Emergencies; 3. Integrated Advanced Distributed Learning capability; 4. NATO/PFP Interoperable; 5. Detailed coordinated planning and execution - Requirements Analysis through M&S Master Plan; 6. National ability to independently sustain and maintain the M&S system. The scope of this plan covers current, developmental and future M&S and ADL systems. It addresses Uzbek Armed Forces needs in the principal application areas of training and exercises, defense planning and analysis, combat and security operations, military support for civil emergencies, research, technology development, and military equipment acquisition., See also ADM001655. Presented at the RTO NMSG Conference on "NATO-PjP/Industry/National Modelling and Simulation Partnerships", held in Paris, France on 24-25 October 2002. Published in RTO-MP-094. Prepared in cooperation with U.S. Modeling and Simulation Information Analysis Center, Alexandria, VA. The original document contains color images.

In the year 2000, representatives from the U.S. Joint Forces Command (USJFCOM), U.S. NAVAIR Orlando Training Systems Division (TSD), and U.S. Army Simulation, Training, and Instrumentation Command (STRICOM), working on different programs but supporting the same Partnership for Peace (PfP) nations, discovered that they had overlapping goals and were using common resources. Representatives from these organizations decided they could better serve U.S. interests, save resources, and provide more capable, integrated and interoperable systems if they coordinated their efforts. Another impetus to working cooperatively was the establishment of USJFCOM as the lead agent for the Regional Security Cooperation Network (RSCN). The RSCN was designed to facilitate coalition-based distributed education and training, building on existing information technology efforts. As a result, representatives from these three organizations decided to form the Enterprise Team to better cooperate while implementing their individual programs. This informal team meets periodically to brief the members on their individual programs and look for ways to support each other's security assistance programs. The Enterprise Team's primary product is integrated, interoperable systems that support national security objectives and facilitate international cooperation. The U.S. Air Force Electronic Systems Center and U.S. Modeling and Simulation Information Analysis Center (MSIAC) joined the team in 2001 and 2002, respectively. Of note, each organization maintains control of its programs while supporting the overall team objectives. The benefits of Enterprise Team activity are clear: each organization brings unique capabilities and different perspectives, resulting in a Big Picture approach to meeting national and regional security objectives. The remainder of the paper outlines the key security assistance programs supported by the Enterprise Team organizations. Ten briefing charts are included. (4 refs.) 7, See also ADM001655. Paper presented at the RTO NMSG Conference on "Nato-PfP/Industry/National Modelling and Simulation Partnerships," held in Paris, France, on 24-25 Oct 2002. Published in report number RTO-MP-094. Prepared in collaboration with the U.S. Army Simulation Training and Instrumentation Command, Orlando, FL; U.S. Modeling and Simulation Information Analysis Center, Alexandria, VA; NAVAIR Orlando Training Systems Division, Orlando, FL; and the U.S. Air Force Electronic Systems Center, Hanscom AFB, MA. The original document contains color images.