DOD/ARMY STTR 2011.A 2

OBJECTIVE: To develop an integrated software tool for the collection, management, analysis, and visualization of ethnographic data in high risk areas. DESCRIPTION: The collection and analysis of socio-cultural data is becoming increasingly important for the conduct of effective military operations. The production of more scientifically valid models of human behavior has itself become increasingly dependent on available forms of socio-cultural data. The ability to rapidly collect social and cultural data in field settings is challenging under most circumstances. In conflict, denied or high risk areas these challenges become even more pronounced. This approach under non-conflict conditions has been variously referred to as rapid ethnographic assessment, quick ethnography, or simply rapid ethnography. Currently, there is little in the way of appropriate software for the conduct of rapid ethnographic research. The ethnographic software that does exist generally involves a series of standalone packages that lack the ability to move data easily among and between programs. There is a critical need for the development of an integrated software tool for enabling the collection, analysis, management, sharing and visualization of ethnographic data in denied or high risk areas. The tool should incorporate a number of ethnographic methods for the rapid collection of cultural, social and economic data based on structured and semi-structured interviews, qualitative text sources, or unobtrusive observations. The software tool will incorporate methods from cognitive anthropology and other social sciences and should include but is not limited to: 1) cultural domain analysis (CDA), 2) social network analysis (SNA), 3) structured and semi-structured interview protocol design, 4) key informant interview mapping, 5) qualitative data analysis (QDA), 6) basic geographical information systems (GIS), 7) data visualization, and 8) basic statistics. Further, the software tool should be usable and understandable by a broad community within the military and should enable better decision-making at various levels (policy, combat operations), real-time computer based cultural situational awareness for tactical decision-making, integrated data and modeling in situ for rapid socio-cultural assessment, training in ethnographic methods, data reducibility and comparability over time and across sites, and continuity and smooth transitioning of data and knowledge across individuals, teams and organizations. PHASE I: Identify and design software in line with required methods and capabilities. All methods and relevant algorithms should be identified and documented. Design should include both stand alone and web-based capabilities. PHASE II: Develop and test prototype software. Test will involve relevant data contexts and personnel. PHASE III DUAL USE APPLICATION: This software can be used in both military and civilian research and training contexts. The software should be of use to human Terrain Systems (HTS), Civil Affairs (CA), Provincial Reconstruction Teams (PRT), and various other military organizations. The software should also be appropriate for training in ethnographic methods in both military and civilian contexts. REFERENCES: 1. Bernard. H. R. and G. W. Ryan. 2010. Analyzing Qualitative Data: Systematic Approaches. Newbury Park, CA: Sage Publications. 2. Borgatti, S. P., 2002. Netdraw: Network Visualization Software. Harvard: Analytic Technologies. 3. Borgatti, S. P. 1999. Elicitation techniques for cultural domain analysis. In J. Schensul & M. LeCompte (Eds.), The Ethnographer"s toolkit, vol. 3. Walnut Creek: Altamira Press. 4. Handwerker, P. 2001. Quick Ethnography. Walnut Creek, CA: AltaMira Press. 5. Johnson, J.C. 1990. Selecting Ethnographic Informants. Sage: Newbury Park. 6. Weller S. and Romney A. 1988. Systematic Data Collection. Sage Publications, Qualitative Research Methods Series, 10.

OBJECTIVE: Exploration of alternative approaches to generate hydrogen from methanol without thermal reforming. Current thermal reformers operate at elevated temperatures. Novel methanol electrolysis processes that converts methanol into hydrogen for use in low power fuel cells will be developed. DESCRIPTION: Current low power Army Fuel cells that are being developed either steam reform methanol to generate hydrogen for subsequent use in a fuel cell or directly convert the methanol into electrical power in direct methanol fuel cells. Thermal reforming increases system complexity and thermal signature while DMFC require large over potentials for methanol oxidization. In addition methanol has the tendency to transport through polymer electrolyte membranes (PEM) with three negative consequences: 1. Methanol at the cathode acts to depolarize the cathode, further reducing the cell potential, and with it the electrical energy yield. 2. Methanol that is not oxidized at the anode does not contribute to the current delivered by the fuel cell. 3. Methanol that is consumed at the cathode yields additional water and carbon dioxide increasing the air flow required for operation. In addition, in current DMFCs trace amounts of ruthenium from the anode diffuses through the membrane and gradually poison the cathode for oxygen reduction. Methanol electrolysis offers a potential a low temperature approach to generate hydrogen efficiently from methanol to circumvent the inefficiencies associated with methanol crossover /ruthenium poisoning and the system complexity and thermal signature of traditional steam reforming. Because the potential required to convert methanol to hydrogen is less than the over potential to oxidize it in a fuel cell, electrolytic reforming has the potential to realize enhanced energy yield due to an increase in overall system potential. In addition, while a conventional DMFC typically operates on dilute methanol, 3 molar or less, with an electrolyzer included in the system methanol can be supplied as an equimolar mixture of methanol and water. PHASE I: Methanol electrolysis will be demonstrated using advanced electrocatalysts and the products characterized. Efficiency will be characterized to show improved performance over state of the art direct methanol fuel cells. Concepts to integrate the electrolyzer into a fuel cell system will be developed. PHASE II: In phase II, based on the results from the successful phase I program, two 25W methanol electrolysis fuel cell systems with performance exceeding current state of the art direct methanol fuel cell systems will be developed and delivered to the US Army for testing and evaluation. PHASE III DUAL USE APPLICATIONS: Advanced methanol electrolysis hydrogen generation technology for fuel cells will significantly impact both military and commercial applications, accelerating product development, particularly for lightweight low power devices. Because the market and the number of devices in the commercial sector is much larger than the military market, widespread usage of this technology will drive down the cost of devices for the military and ensure a reliable manufacturing base. The methanol electrolysis technology will transition into fuel cell system technology for dismounted soldiers. Likely sources of funding if the phase III program is successful include PEO Soldier and CERDEC. Applications for the advanced methanol fuel cell systems include soldier power to complement batteries and to charge lithium-ion rechargeable batteries, significantly reducing the logistical burden (weight and volume) for the soldier by reducing the number of batteries required for extended mission time as well as a many civilian electronics applications. REFERENCES: 1. Z. Hu, M. Wu, Z. Wei, S. Song, and P. K. Shen, J. Pow.., 166, 458-461 (2007). 2. G. Sasikumar, A, Muthumeenal, S. Pethaiah, N. Nachiappan, and R. Balaji, Int. J. Hyd. Energ., 33, 5905 5910 (2008). 3. R. F. de Souza, G. Loget, J. C. Padilha, E. M. A. Martini and M. O. De Souza, Electrochem. Comm., 10, 1673 1675 (2008). 4. T. Maiyalagan, Int. J. Hyd. Energy., 34, 2874 2879 (2009). 5. T. Take, K. Tsurutani, and M. Umeda, J. Pow. Sourc., 164, 9 16 (2007). 6. Barbara Jeffries-Nakamura, Sekharipuram R Narayanan, Thomas I Valdez, William Chun, NASA TECH BRIEF Vol. 26, No. 6 from JPL NEW TECHNOLOGY REPORT NPO- 19948 (2002).

OBJECTIVE: Develop new biomimetic membranes with chemical stability and reduced methanol crossover to enable micro direct methanol fuel cells (DMFCs). DESCRIPTION: The Army has need for high-energy density, lightweight power sources for the dismounted warrior. Currently methanol fueled polymer electrolyte based fuel cells suffer from methanol cross over which reduces overall system efficiency and necessitates the use of diluted methanol solutions decreasing the system specific energy. Biomimetic membranes with ion channels either inspired by natural systems or membranes with channels from organisms offer several potential advantages including improved conductivity and selective permeability. At the same time bioderived systems represent several challenges including: chemical stability, dehydration, the ability to integrate bioderived materials into synthetic membranes, and the challenges of orienting and aligning pores to allow their use in thicker mechanically robust membranes. PHASE I: In phase I biomimetic membranes will be produced and evaluated to demonstrate feasibility for use in fuel cells. Specific goals should include the ability to prepare mechanically robust membranes that have conductivities on par with their Nafion based counterparts, reduced methanol crossover, chemical stability when exposed to high methanol concentrations which can both denature and dehydrate the biomimetic pores, and evaluate the membrane in a direct methanol half cell. Preliminary results should support the potential to develop a robust 1W system which can utilize 15M or higher methanol solutions with reduced methanol crossover. PHASE II: In phase II, based on the results from the successful phase I program, design, construct, and evaluate a DMFC 1W passive fuel cell with a stack based on biomimetic membranes. The system must have a lifetime exceeding 500 hours, a system energy density exceeding 1500 Wh/kg, and be able to directly utilize concentrated methanol (>15M). Two systems will be delivered to the US Army for testing and evaluation. PHASE III: Biomimetic membranes will be integrated into larger power fuel cell stacks for both military and civilian power applications. These systems will have higher efficiencies and lighter system weights than the current state of the art systems. Bothe the military and civilian sectors are seeking compact light weight power sources for dismounted soldiers and civilian electronic devices. The biomimetic membranes for DMFCs have the potential to transition to both soldier borne and solider transportable applications to either power devices directly on the soldier or to serve as a power source to recharge secondary batteries. Likely sources of funding if the phase III program is successful include PEO Soldier and CERDEC. REFERENCES: 1. Xie, C., J. Bostaph, and J. Pavio. 2004. Development of a 2 W direct methanol fuel cell power source. Journal of Power Sources 136:55-65. 2. Broussely, M., and G. Archdale. 2004. Li-ion batteries and portable power source prospects for the next 5-10 years. Journal of Power Sources 136:386-394. 3. Kim, D. J., E. A. Cho, S. A. Hong, I. H. Oh, and H. Y. Ha. 2004. Recent progress in passive direct methanol fuel cells at KIST. Journal of Power Sources 130:172-177. 4. Shimizu, T., T. Momma, M. Mohamedi, T. Osaka, and S. Sarangapani. 2004. Design and fabrication of pumpless small direct methanol fuel cells for portable applications. Journal of Power Sources 137:277-283. 5. Kim, H. 2006. Passive direct methanol fuel cells fed with methanol vapor. Journal of Power Sources 162:1232-1235. 6. Gupta, G., P. Atanassov, and G. P. Lopez. 2006. Robust hybrid thin films that incorporate lamellar phospholipid bilayer assemblies and transmembrane proteins. Biointerphases 1:6-10. 7. Montal, M., and P. Mueller. 1972. Formation of Bimolecular Membranes from Lipid Monolayers and a Study of Their Electrical Properties. Proceedings of the National Academy of Sciences of the United States of America 69:3561-3566. 8. Ly, H. V., and M. L. Longo. 2004. The influence of short-chain alcohols on interfacial tension, mechanical properties, area/molecule, and permeability of fluid lipid bilayers. Biophysical Journal 87:1013-1033. 9. Lee, W., H. Kim, T. K. Kim, and H. Chang. 2007. Nation based organic/inorganic composite membrane for air-breathing direct methanol fuel cells. Journal of Membrane Science 292:29-34. 10. Akeson, M., and D. W. Deamer. 1991. Proton Conductance by the Gramicidin Water Wire - Model for Proton Conductance in the F1F0 ATPases. Biophysical Journal 60:101-109.

OBJECTIVE: Develop a fungal protein expression system with integrated purification scheme for low-cost production of purified, functional Chloroperoxidase in kilogram quantities. DESCRIPTION: Chloroperoxidase (CPO) is an enzyme produced by certain fungal species that catalyzes a diversity of biochemical reactions. For example, the CPO produced by the filamentous fungus Caldariomyces fumago catalyzes the non-specific halogenation, including chlorination, bromination and iodation, of electrophilic organic molecules. In the absence of halide, CPO is similar to the cytochrome P450 enzymes in its epoxidation and hydroxylation of olefins and organic sulfides. A CPO recently identified in the fungus Agrocybe aegerita has been shown to carry out both benzylic and aromatic hydroxylation. The versatile catalytic properties of CPO have application in paper bleaching and potential application as active ingredients in cleaning supplies and in detection and inactivation of chemical agents or products on environmental surfaces. C. fumago CPO is ideally suited for the inactivation of chemical agents due to its exceptional stability, broad substrate profile, and high catalytic efficiency. However, the high cost of producing large amounts of CPO endogenously from fungal hosts is a major obstacle precluding the formulation and field deployment of enzyme systems for chemical agent decontamination. Therefore, an advanced technology is needed that will enable the large-scale and economical production of CPO in a highly active form. Expression in heterologous host systems, including Escherichia coli, insect cells, Saccharomyces cerevisiae, and Pichia pastoris, is hindered due to the complex post-translational modifications required for CPO activity. Therefore, the goal of this topic is to develop an expression system in filamentous fungi, either by enhancing endogenous expression or developing an exogenous expression system. Protein production capacity as well as economic enzyme purification technology will be critical in achieving the required kilogram-scale manufacturing capabilities. Field application of a CPO-based decontamination system is projected to require a cost of enzyme production at or below $0.025/1000 enzyme units. PHASE I: Develop a fungal expression system and purification scheme to produce milligram quantities of CPO at a purity of 90% or greater. Perform detailed biochemical characterization of the purified enzyme, including determination of catalytic efficiency and enzyme stability under a range of proposer-defined reaction conditions suitable for use in field technologies. PHASE II: Optimize the fungal expression system and purification scheme to demonstrate production of kilogram quantities of CPO at a purity of 90% or greater. The purified enzyme must exhibit native activity levels. Enzyme production should be achieved for a cost at or below $0.025/1000 enzyme units. Proper batch record documentation and quality control processes should be demonstrated. PHASE III DUAL USE APPLICATIONS: The development of a high-capacity cost-effective fungal production system for chloroperoxidase will suport capabilities in enzymatic-based field technologies. The proposer should identify appropriate transition or collaborative partners who will use this enzyme in development and fielding of technology that supports the warfighter mission (e.g., chemical decontamination technologies). The economic production of chloroperoxidase may also be beneficial in the commercial sector (e.g., remediation technologies with Hazmat teams, paper industry, etc.). REFERENCES: 1) Manoj, K. M. and L. P. Hager. 2008. Chloroperoxidase, a Janus enzyme. Biochemistry 47:29973003. 2) Hernandez J., N. R. Bobledo, L. Velasco, R. Quintero, M. A. Pickard and R. Vazquez-Duhalt. 1998. Chloroperoxidase-mediated oxidation of organophosphorus pesticides. Pest. Biochem. Physiol. 61:8794. 3) Ayala M., M. A. Pickard and R. Vazquez-Duhalt. 2008. Fungal enzymes for environmental purposes, a molecular biology challenge. J. Mol. Microbiol. Biotechnol. 15:172180. 4) Conesa, A., F. van de Velde, F. van Rantwijk, R. A. Sheldon, C. van den Hondel, and P. J. Punt. 2001. Expression of the Caldariomyces fumago chloroperoxidase in Aspergillus niger and characterization of the recombinant enzyme. JBC 276:17635-17640.

OBJECTIVE: The objectives of this STTR are to investigate numerical methods for predictably-accurate treatment of boundary conditions in electromagnetic and other wave-dominated phenomena, and to develop algorithms and computer software that can be implemented for military and commercial simulation applications. DESCRIPTION: High fidelity modeling of electromagnetic phenomena has become increasingly important in the design and virtual prototyping of navigation, detection, tracking, and communications systems, helping simulation become widely recognized as the third major component of scientific discovery and development, co-equal with experimentation and theory [9]. However, the simulation of electromagnetic phenomena in the time-domain poses unique computational challenges; these systems are hyperbolic with propagation length scales that are many orders of magnitude greater than the wavelength. Although new algorithmic developments have greatly improved the reliability and efficiency of approximations to Maxwell"s equations within the computational domain [5,6], a major obstacle to accurate long-time solutions is the presence of spurious reflections which occur at the computational boundaries and back-propagate to degrade the solution over the interior. The large propagation length scale makes it impossible to compute over a domain that is large enough that boundary reflections are so far removed as to be insignificant [4]. The widely accepted solution to this problem is to implement algorithms at the boundary which attempt to introduce precisely the right amount of artificial damping (a"perfectly matched layer", or PML) so that incident waves are rapidly damped with no reflection. [3] These models suffer from several deficiencies. They are very problem-specific; every problem, domain, geometry, source and receiver location, etc. has to be treated individually and the PML has to be adjusted for each so as to minimize reflections for that particular case. In addition, every new model requires a new PML, and no general procedure is known to construct a priori stable and accurate layers [2]. Thus in practice, PMLs rely on empirical parameters that must be set by trial and error. This fact hinders the development of high fidelity models; error bounds applicable to the stretched layers required for efficient computations are unknown, and so uncertainties in the error at boundaries propagate into the interior and degrade the accuracy and/or reliability of our computations. With the advent of scalable parallel processing architectures, the need has become apparent for new algorithms that can control reflections at boundaries, can give us guaranteed error bounds so that we can achieve guaranteed high fidelity modeling of these important applications, and can determine a priori the computational load (number of terms required, order of approximation required, etc) to achieve a specified and guaranteed level of accuracy. While some work has been done in a priori methods for nonreflecting boundaries (e.g. [1,7,8]), most of the results to date are restricted to simple artificial boundaries which may be wasteful of computational volume and also require the discretization of nonstandard operators. In particular their implementation using standard methods in the interior has not been demonstrated. What is needed is development of an a priori, error-bounded algorithm that can be encoded in a standard software routine or set of routines and that can be distributed within standard high performance computing (HPC) libraries or computational electrodynamics packages for simulation on parallel, distributed, and Grid-based computing platforms. To ensure the fidelity of simulations and introduce guaranteed error bounds, without intervention or coding by experts, for military and commercial simulations, it is imperative that 1) the various existing techniques for treating computational boundaries for electrodynamics and other wave systems be investigated; 2) efficient numerical methods and their algorithms be developed for minimizing wave reflections at boundaries; 3) prototype computer software for the algorithms be developed for military and commercial applications in computational environments. In order to transfer the technology for commercial use, it is proposed that business technical staffs and university researchers be involved in both the investigation of the numerical methods and the development of the software. It is proposed that the program be carried out in the following two phases. PHASE I: In Phase I the following shall be accomplished: a. A complete assessment of currently available numerical methods and algorithms for reflection control at computational boundaries. b. Development of domain boundary methods for inclusion in standard computational electrodynamics packages. c. Development of methods for the automatic generation of boundary handling, establishment of guaranteed a priori bounds on the error due to reflections, and establishment of the guaranteed resulting computational load. d. Development of new algorithms that are suitable for real time parallel and/or distributed computing environments. PHASE II: In Phase II, a. Computer coding of the algorithms developed in Phase I shall be done primarily by software engineers in private industries and some by university researchers. b. The reliability of the algorithm will be demonstrated by testing on a comprehensive suite of community-recognized benchmark problems. c. The possibility of stably coupling the boundary algorithm with all standard volume discretization techniques will be demonstrated. d. The efficiency of the implementation will be demonstrated by testing on a variety of representative architectures. e. A standard HPC version will be released with licensing requirements for commercial users that incorporates the multi-core and GPU algorithms. f. A complete set of documentation regarding the theoretical results, software design, and implementation shall be delivered with the prototype software to the military for evaluation and implementation at US Government HPC centers, including DoD Major Shared Resource Centers. It shall also be made commercially available to HPC users at academically oriented HPC centers. g. A long-term sustainability plan for development, maintenance and support of the software based on revenue estimates will be developed. h. A website will be launched for the distribution and support of the software to both commercial and noncommercial users. i. A stable support infrastructure to deal with both new and existing users will be created. Support will be maintained that is capable of dealing with installation issues over many platforms as well as bug resolution and usage issues with the existing code base. This will not only include standard release mechanisms, but also a web-based help center that directly interacts with users. PHASE III DUAL USE APPLICATIONS: The technology developed under this topic will improve the performance of software for computational electromagnetics and eliminate the need for empirical parameters for the design of boundary conditions. This will enable a significant reduction in the design cycle time of military electromagnetic systems for ground mobile wireless communications and sensing. The technology will bring similar benefit to system development for applications in commercial wireless networking and communications. REFERENCES: 1. B. Alpert, L. Greengard, and T. Hagstrom, Nonreflecting boundary conditions for the time-dependent wave equation, J. Comput. Phys., 180:270-296, 2002. 2. E. Becache, S. Fauqueux, and P. Joly, Stability of perfectly matched layers, group velocities, and anisotropic waves, J. Comput. Phys., 188:399-433, 2003. 3. J.-P. Berenger, A perfectly matched layer for the absorption of electromagnetic waves, J. Comput. Phys., 114:185-2000, 1994. 4. T. Hagstrom and S. Lau, Radiation boundary conditions for Maxwell"s equations: a review of accurate time-domain formulations, J. Comput. Math., 25:305-336, 2007. 5. W. Henshaw, A high-order accurate parallel solver for Maxwell"s equations on overlapping grids, SIAM J. Sci. Stat. Comp., 28:1730-1765, 2006. 6. J. Hesthaven and T. Warburton, High order/spectral methods on unstructured grids. I. Time-domain solution of Maxwell"s equations, J. Comput. Phys., 161:331-353, 2002. 7. C. Lubich and A. Schadle, Fast convolution for nonreflecting boundary conditions, SIAM J. Sci. Stat. Comp., 24:161-182, 2002. 8. V. Ryaben"kii, S. Tsynkov, and V. Turchaninov, Global discrete artificial boundary conditions for time-dependent wave propagation, J. Comput. Phys., 174:712-758, 2002. 9. Computational Science: Ensuring America"s Competitiveness, President"s Information Technology Advisory Committee, 2005.

OBJECTIVE: To develop molecular beam epitaxy/ chemical vapor deposited (MBE/CVD or MOCVD) low-loss, tunable complex oxide thin film materials to enable compact, switchable FBAR filters operating in the 1-3 GHz frequency range. DESCRIPTION: In modern communication systems, frequency-agile and reconfigurable components are becoming increasingly necessary to cope with a multitude of signal frequencies and modulation formats. Acoustic resonator devices are currently the technology of choice for compact front-end filtering since they are not limited by the inductor resonator quality (Q) factors. Historically, surface acoustic wave (SAW) resonators have been used, which in recent years have given way to Film Bulk Acoustic Resonator (FBAR) technologies. Such acoustic devices exploit piezoelectric materials (such as AlN, ZnO) and when properly designed can have extremely high Q-factors of 600 or more at RF frequencies; hence high-order, low-loss filters can be realized. However, the resonance frequency of an FBAR resonator is determined by the thickness of the piezoelectric material, and is thus fixed. Since an FBAR device has a high Q-factor, it is difficult to pull or de-tune this resonant frequency with external components like varactors unless the devices are heavily loaded, which then degrades the Q. Thus, in order to achieve frequency agility or re-configurability, multiple FBAR filters must be combined with a switching network to route the signal through an appropriate fixed-frequency filter. It has recently been shown that electrostrictive materials as well as materials that show DC-voltage induced piezoelectricity can be utilized as both a switch and a resonator if configured properly [1-5]. This eliminates the need for complex and lossy switching networks in frequency-agile filter networks. This switchable FBAR technology is enabled by perovskite oxide materials, specifically BaSrTiO3 (BST) and SrTiO3, which have been shown to have coupling constants comparable to that of AlN, which is the current material used in FBAR. The quality of FBAR devices is highly sensitive to film quality and crystal orientation. As is well-established in semiconductor technology, molecular beam epitaxy offers the highest quality thin film materials and excellent control over film orientation. It has been recently shown that high-quality perovskite oxide thin films, such as SrTiO3, can be grown by MBE [6]. It is anticipated that by using advanced growth techniques (which are standard to the electronics industry for growing III-V compound semiconductors), such as, Molecular Beam Epitaxy (MBE) and/or Chemical Vapor Deposited (CVD) or Metallo Organic CVD - thin films of BST or SrTiO3, switchable FBAR of unprecedented quality will be obtained. The goal of this STTR is to investigate the feasibility of using of high-quality MBE/CVD electrostrictive oxide films for switchable FBAR devices and filters. PHASE I: The offerer will demonstrate feasibility to deposit high-quality films of BST and SrTiO3 films using MBE/CVD or MOCVD. Thin film quality metrics include the demonstration of high quality stoichiometric films with smooth interfaces and low dielectric losses. The Phase 1 work should also include full characterization of the FBAR process; including (i) identifying the challenges relating to the processing temperatures and (ii) identification of a route to commercial processing. The offerer will design a FBAR device utilizing a switchable perovskite oxide FBAR from 1-3 GHz and predict its performance. PHASE II: The offerer will deposit high quality perovskite oxide based films consistently by MBE/CVD or MOCVD and conducts full characterization of these films. These films will then be optimized and processed into FBAR devices with detailed material analysis and processing characterization performed to understand how material/film orientation affects the FBAR performance. Material deposition parameters will be varied with the goal to evaluate how they impact the FBAR properties. Filters will be fabricated utilizing the FBAR devices and full RF characterization of the filters will be performed including filter shape performance, linearity, harmonics, Q, loss, return loss, group delay, etc. in order to compare with existing technology. The ability to switch on and off will be demonstrated. Initial reliability and lifetime testing will also be performed to baseline the robustness of the process and design. PHASE III DUAL USE APPLICATIONS: Phase III will involve refinements of the filter design and include specifically designed filters and packaging for use in actual systems. Documentation to ISO standards and refinement of the manufacturing processes will be performed and repeated to establish a commercially scalable manufacturing process. Additional reliability testing will be performed to conform to commercial and military standard test practices. This filter technology can be utilized in a number of high frequency communications systems for both the military and commercial use. REFERENCES: [1] K. Morito, Y. Iwazaki, T. Suzuki, and M. Fujimoto,"Electric field induced piezoelectric resonance in the micrometer to millimeter waveband in a thin film SrTiO3 capacitor", J. Appl. Phys. 94, 5199 (2003). [2] S. Tappe, U. Bttger, and R. Waser,"Electrostrictive resonances in Ba0.7Sr0.3TiO3 thin films at microwave frequencies", Appl. Phys. Lett. 85, 624 (2005). [3] A. Noeth, T. Yamada, A. K. Tagantsev, N. Setter, Electrical tuning of dc bias induced acoustic resonances in paraelectric thin films, J. Appl. Phys. 104, 094102 (2008). [4] J. Berge, A. Vorobiev, W. Steichen, S. Gevorgian, Tunable solidly mounted thin film bulk acoustic resonators based on BaxSr1-xTiO3 films, IEEE Microwave Wireless Comp. Lett. 17, 655 (2007). [5] G. N. Saddik, D. S. Boesch, S. Stemmer, R. A. York, DC electric field tunable bulk acoustic wave solidly mounted resonator using SrTiO3, Appl. Phys. Lett. 91, 043501 (2007). [6] J. Son, P. Moetakef, B. Jalan, O. Bierwagen, N. J. Wright, R. Engel-Herbert, S. Stemmer, Epitaxial SrTiO3 films with electron mobilities exceeding 30,000 cm2V-1s-1, Nature Mater. 9, 482 (2010).

OBJECTIVE: The development of a compact and portable instrument that couples mass spectrometry and Rydberg spectroscopy to provide a complete"fingerprint"of a molecule, including molecular mass as well as isomeric and conformeric identification. This instrument will enable a major increase in selectivity for threat identification in the field, while minimizing sample consumption, as well as instrument footprint and cost. DESCRIPTION: Mass spectrometers (MS) are powerful and widely used tools for molecular analysis in chemical and pharmaceutical industries, for environmental analysis, in forensic labs, and in basic research. However, the standard instruments have two primary drawbacks for application in-the-field 1) inability to rapidly identify isomers and conformers of molecules of interest and 2) its size; they are often large cumbersome instruments. In recent years it has been shown that excited electronic (Rydberg) states could distinguish among molecular shapes (isomers) for several different atomic compositions. Laser-induced Rydberg spectra could provide"fingerprints"that, when joined with MS molecular mass spectra, would enable unambiguous identification of molecular structures (isomers) and, further, different molecular shapes (conformers) of the same isomer. Recent advances in MS have also lead to reduction in instrument footprint size. This call seeks to push the limits of MS miniaturization while simultaneously coupling it to Rydberg Spectroscopy, resulting in a compact, self-contained unit for increased discrimination of chemical and biological threats PHASE I: (Feasibility Study) Demonstrate coincident measurement of mass spectra and Rydberg ionization for a set of molecular isomers. Demonstrate design for two-dimensional coincidence Rydberg and mass spectra for complete signature fingerprint. Develop designs for miniaturized Rydberg/MS detectors. Design criteria must include: simplicity and minimum number of parts, ruggedness and sensitivity. Provide cost estimate for instrument. PHASE II: (Prototype Delivery) Build prototype Rydberg/MS detection unit using designs from Phase I. Demonstrate coincidence operation for isomer identification. Provide validation data on maximum mass range. Determine sensitivity of instrument and ability to identify threat agents against a large background of volatile organic compounds. PHASE III DUAL USE APPLICATIONS: The miniaturization of mass spectrometry coupled to Rydberg spectroscopy is an attractive concept for an advanced chemical/biological sensor which can identify and distinguish between isomeric forms of the same compound. This phase of the project will couple mass spectrometry to Rydberg spectroscopy. The impact of this work would provide modern labs with the ultimate analytical tool for rapid, unambiguous identification of any analyte, from environmental toxins to biologically active pharmaceuticals and beyond. Consequently the commercial potential of the end product would be enormous, rivaling NMR and current tandem mass spectroscopic techniques, which are expensive, cumbersome and lack sensitivity. REFERENCES: 1. Gosselin and Weber,"Rydberg Fingerprint Spectroscopy: A New Spectroscopic Tool with Local and Global Structural Sensitivity", J. Phys. Chem. A 2005, 109, 4899-4904 2. Cardoza, Rudakov, Fedor, Hansen, and Weber,"Identification of Isomeric Hydrocarbons by Rydberg Photoelectron Spectroscopy", Journal of Electron Spectroscopy and Related Phenomena 2008, 165, 5 - 10. 3. Minnitti and Weber,"Time-Resolved Conformational Dynamics in Hydrocarbon Chains", Physical Review Letters 2007, 98, 253004. 4. Kuthirummal and Weber,"Structure Sensitive Photoionization via Rydberg Levels", Journal of Molecular Structure 2006, 787, 163 - 166.

OBJECTIVE: The goal of the research is to demonstrate the feasibility of using thin-film multiferroic heterostructures as magneto-electric tunable RF isolators at frequencies above 10 GHz. DESCRIPTION: Magnetic-field tunable ferrite devices are currently used as resonators, filters, phase-shifters, circulators, isolators. Unfortunately, the tuning response times limit their use at higher frequencies, and the material losses and device noise characteristics are becoming unacceptable. Further, they are incompatible with RF semiconductor IC technology and have relatively high power requirements. Multiferroic materials have the potential to greatly improve on these properties and provide a viable solution for electrically tuned ferromagnetic RF resonance devices. The additional design space gained from exploiting either magnetically-modulated piezo-electric fields or electrically-modulated piezomagnetic fields could greatly expand the range of tuning in integrated microwave circuitry, resulting in RF systems that are much lighter, smaller, reliable and more affordable than current devices and systems. Single-phase multiferroics exhibit intrinsic magnetoelectric effects that are too small for RF device applications at frequencies of interest for military systems. However multilayered multiferroic hetero-structures can be engineered to simultaneously possess a net magnetic moment and an electric polarization that can then interact through a strain-induced coupling of the constituent lattice polarization field and magnetic domain ordering. Layered structures with large magnetoelectric effect have been demonstrated on a limited basis, e.g. bilayers with ferrites as the piezomagnetic phase and BST or PZT as the paraelectric phase.1) In particular, hexagonal ferrites (BaM) are also available and are magnetically self-biasing, which can allow for the design of enhanced ME effects and devices for operation at higher frequencies without the need for heavy and expensive magnets.2) PHASE I: Proposers should demonstrate a viable thin-film deposition technology for multiferroic heterostructures and then investigate the magneto-electric properties of the heterostructures in order to evaluate the feasibility of developing a magneto-electrically tunable RF isolator. The research should seek to develop a systematic understanding of the physics and high frequency behavior of the hybrid modes that arise in multiferroic heterostructures, and demonstrate the feasibility of establishing electronic control of the magnetic response of these hetero-ferroic film composites with minimal associated losses and noise. PHASE II: The small business should implement the processing innovations identified in Phase 1. Based on these studies the program should develop a methodology for achieving high speed tuning with the widest magneto-electric frequency range at the lowest applied electric field. This phase should include the production and testing of prototype devices. Phase 2 effort should optimize the materials and processing parameters for production of energy efficient, tunable RF isolators capable of operating at frequencies above 10 GHz and across the full military temperature range of -20 C to +125 C. PHASE III DUAL USE APPLICATIONS: Magnetic-field tunable ferrite devices are currently used in resonators, filters, phase shifters, circulators. Unfortunately, tuning response times are limited and the devices display rather large loss and noise characteristics. The present program will seek to introduce a new multiferroic technology that will provide improved microwave devices with superior tunability and overall performance standards. REFERENCES: 1) R.V. Petrov, A.S. Tatarenko, G. Srinivasan and J.V. Mantese,"Antenna Miniaturization with Ferrite-Ferroelectric Composites", Microwave and Optical Technology Lttrs, 50, 12 (December 2008), p. 3354-7 2) A.B. Ustinov and G.Srinivasan,"Subterahertz excitations and magnetoelectric effects in hexaferrite-piezoelectric bilayers", APL, 93, 142503 (2008).

OBJECTIVE: The objective of this STTR is to develop a machine that will reliably train small animals to detect explosives or other compounds of interest and will provide an objective unbiased measurement of the animal"s sensitivity and accuracy. DESCRIPTION: The Army is engaged in extensive humanitarian demining efforts. Demining is often necessary to restore farm land to agricultural use, and to enable societies to stabilize after war. Although dogs are the most commonly used animal for mine detection, it has been demonstrated that other animals can reliably smell mines, and smaller animals have advantages over dogs in some situations. The cost of training animals to detect mines is primarily due to the human labor involved. In addition, the actual training of animals to detect mines remains as much of an art as a science. It is desirable to 1) have an automated training system that reduces the human labor cost, and 2) have an automated scoring system that objectively measures the animal"s accuracy and sensitivity. Because much of the demining efforts are happening in third world countries with little access to engineering expertise or parts, this system must be rugged, reliable, inexpensive, simple to operate, and easy to fix. PHASE I: The investigators will design a system to reliably train small animals to detect mines and to objectively evaluate and score their performance. At the end of phase I they will present detailed plans for this system. Phase I will be evaluated on the basis of the proposed system to effectively train and evaluate small animals, and on cost, ruggedness, reliability, simplicity, and ease of maintaining and repairing the system. The system should be usable by animals up to 7 kg. PHASE II: The investigators will build prototype systems and will deliver at least five of these prototypes to locations to be designated by the program manager for field testing. By the end of phase II the investigators will have developed the capability for large scale production of Rugged Automated Training Systems. PHASE III DUAL USE APPLICATIONS: The investigators will produce and sell large numbers of these Rugged Automated Training Systems for worldwide use. Mines are widespread throughout much of Africa, Asia, and Central America and demining operations are expected to continue for decades. Finding and removing mines is necessary to restore mined land to civilian use. REFERENCES: 1) Catania, KC, and Remple, FE. 2004. Tactile foveation in the star-nosed mole. Brain Behav Evol 63(1):1-12. 2) Verhagen, R, Weetjens, F, Cox, C., and Weetjens, B. 2006. Rats to the Rescue: Results of the First Tests on a Real Minefield, Journal of Mine Action 9, 2.

OBJECTIVE: Automated techniques for understanding and classifying behavior of novel malware. DESCRIPTION: The number of new malware being encountered in the wild is steadily and rapidly increasing. Recent reports show that more than 5,000 new, unique malware samples are encountered daily. In order to keep pace and not fall behind in the arms race with malware creators, there is a dire need for a systematic, automated way to process this deluge of malware. When a malware is encountered, there are two questions that need to be answered: (i) what does the malware do? (ii) is the malware a variant of an already known malware? Automated and effective techniques combining static and dynamic analysis of executables, mining techniques for behaviors, and malware classification are needed to address this challenging problem. The same technique may also help understand behavior of COTS from untrusted and unknown sources. Researchers are exploring new techniques that can address these questions, such as the recent work on automated construction of dependence graphs from executions of malware for understanding and summarizing the behavior of the malware. Researchers have also studied mining tools and techniques based on dependence graphs to extract the behavior of malware. Semi-automated specification generation techniques have been explored to help analysts construct detection mechanisms for newly discovered malware behaviors for incorporating them into behavior-based or cloud-based malware detectors. Some researchers (such as Bailey et al. 2007) have addressed the malware classification problem: classifying malware by type (e.g., Virus, Worm, Spyware), family (e.g., Bagle, Netsky, MyDoom), and whether it has been encountered before. The current practice of analysts manually inspecting each individual incoming malware is not a sustainable solution. There is a need for proven and deployable automated techniques that can process and analyze large volumes of malware binaries. PHASE I: 1) Research and develop automated malware understanding and classification technologies based on recent new techniques such as dependence graphs or symbolic execution that can effectively and efficiently analyze and characterize malware behavior and to defeat the use of obfuscation and polymorphism. 2) Demonstrate that the proposed techniques can be implemented successfully in classifying behaviors for a large corpus of malware in near real-time. PHASE II: 1) Extend the techniques proposed in phase I to mine or extract relevant behaviors of malware. 2) Develop and implement techniques for automatically transforming the extracted malware pattern and behaviors into policies or patterns that can be ported into existing malware detectors. 3) Validate the techniques under operational conditions. The goal of this phase will be to demonstrate that a new malware can be analyzed near real-time. The goal will be to analyze, classify, and mine behaviors in less than five minutes with minimum human intervention. PHASE III DUAL USE APPLICATIONS: Effective techniques for understanding and classifying malware are critical for both military and commercial sectors. The developed system will be marketed as a malware-analysis platform which will be attractive to malware-detection companies and defense agencies. The malware-analysis platform can be used by agencies and companies for developing a faster defense against zero-day attacks. REFERENCES: 1. B. Acohido and J. Swartz. Zero Day Threat: The Shocking Truth of How Banks and Credit Bureaus Help Cyber Crooks Steal Your Money and Identity. Union Square Press, April 2008. 2. Michael Bailey, Jon Oberheide, Jon Andersen, Z. Morley Mao, Farnam Jahanian, and Jose Nazario, Automated Classification and Analysis of Internet Malware, Proceedings of Recent Advances in Intrusion Detection (RAID'07), September 2007. 3. Mihai Christodorescu, Somesh Jha, and Christopher Kruegel, Mining specifications of malicious behavior, ESEC/SIGSOFT FSE, 2007. 4. Matt Fredrikson, Mihai Christodorescu, Somesh Jha, Reiner Sailer, and Xifeng Yan, Synthesizing Near-Optimal Malware Specifications from Suspicious Behaviors IEEE Symposium on Security and Privacy, 2010. 5. Lorenzo Martignoni, Elizabeth Stinson, Matt Fredrikson, Somesh Jha, John C. Mitchell, A Layered Architecture for Detecting Malicious Behaviors, RAID 2008. 6. Mila Dalla Preda, Mihai Christodorescu, Somesh Jha, Saumya K. Debray, A semantics-based approach to malware detection, ACM Trans. Program. Lang. Syst., 30(5), 2008 7. David Brumley, Hao Wang, Somesh Jha, Dawn Xiaodong Song, Creating Vulnerability Signatures Using Weakest Preconditions, CSF, 2007: 8. Hao Wang, Somesh Jha, Vinod Ganapathy, NetSpy: Automatic Generation of Spyware Signatures for NIDS, ACSAC, 2006.

OBJECTIVE: To build artificial antibodies using DNA origami and develop novel types of electo-optical based biological sensing methodologies. DESCRIPTION: Nature is adept at producing molecules that can recognize and specifically bind to other molecules. In biological systems, antibodies can search out and selectively bind to specific target molecules in the presence of numerous other substances. Antibodies are a critical component of the immune systems of many organisms. Selective binding allows the body"s immune system to target and eliminate specific antigens. Antibodies have also become the gold standard for many biosensing applications. Natural proteins are widely used in diagnostic tests for many diseases because they recognize and efficiently bind to disease markers. Attempts have been made to synthesize molecules with abilities for selective bonding that are comparable to antibodies. However, protein antibodies are difficult and expensive to synthesize in the laboratory. The precise rules of protein folding are still a mystery and are one of the unsolved problems of modern biology. Attempts to manufacture proteins with predetermined shapes and functionality have met with limited success. Protein antibodies are also perishable and possess a short shelf life. Attempts have been made to manufacture antibodies from polymers using molecular imprinting. In molecular imprinting, a solution containing a polymer grows around a target molecule. The target molecule is then washed away. When the molecular imprinted antibody contacts the target molecule, binding occurs. Molecular imprinted antibodies have had some success, However, in the case of biological warfare agents, the use of antigens during the manufacturing process presents a difficult, if not impossible, situation. The folding of single- and double-stranded DNA is a chemically well-understood and controllable process. DNA is generally associated with the storage of genetic information. However, in many ways, it is also an ideal building material. DNA"s sequence dictates its shape and structure. Recently, progress has facilitated cheap and easy manufacturing of DNA strands with custom sequences. The use of self-assembled DNA sequences is thus a very attractive approach in the search for artificial antibodies. The science of DNA origami has recently progressed to the point that it is now possible to design and manufacture complex structures using DNA folding techniques. Much of the science of DNA origami is centered on producing better design software. The ability to produce better design software is a critical component of the controlled design and production large complex structures using DNA origami. PHASE I: Conduct a feasibility study of producing artificial antibodies using DNA origami. Methods should be developed to design structures with predetermined shapes and functions. Methods for manipulating the physical properties of the self-assembled structures should also be examined, and electro-optical testing methods should be defined for verifying the types of physical properties achieved. In particular, methods should be developed to manipulate the charge on the surface of a DNA self-assembled nanostructure. Also, the production of controlled hydrophobic and hydrophilic surfaces should be examined using DNA origami methods. A preliminary design should be made to produce structures using DNA origami that will function as antibodies. Where possible, target antigens related to biological warfare agents or simulants should be used in the initial design studies. PHASE II: Fabricate artificial antibodies using DNA origami. Test the affinity of the antibodies to known antigens. Based on the results of the tests, refine the design of the antibodies. Examine methods for incorporating the new artificial antibodies into sensors specifically designed for the detection and identification of biological warfare agents and simulants. Here, an emphasis should be placed upon defining and refining electro-optical based transduction methodologies for achieving the detection and identification capability. PHASE III DUAL USE APPLICATIONS: Further research and development during Phase III efforts will be directed toward refining final deployable designs for artificial antibodies. Design modifications based on results from tests conducted during Phase II will be incorporated. Manufacturability specific to U.S. Army CONOPS and end-user requirements should be examined. Artificial antibodies will have numerous commercial applications, particularly in the field of medicine. It is expected that commercialization will accelerate once the antibodies become less expensive and easier to use. It is one of the goals of this effort to produce affordable, stable antibodies that can be reliably mass-produced for battlefield applications, especially in the context of biological agent detection and identification. REFERENCES: 1. Gnter Wulff,"Molecular Imprinting in Cross-Linked Materials with the Aid of Molecular Templates - A Way towards Artificial Antibodies", Angewandte Chemie International Edition, volume 34, issue 17, pages 1812-1832, 2003. 2. Yoshitaka Iba and Yoshikazu Kurosawa,"Comparison of strategies for the construction of libraries of artificial antibodies", Immunology and Cell Biology, volume 75, pages 217-221; 1997. 3. Carl A. K. Borrebaeck,"Antibodies in diagnostics from immunoassays to protein chips", Immunology Today, volume 21, issue 8, pages 379-382, 2000. 4. Paul W. K. Rothemund,"Folding DNA to create nanoscale shapes and patterns", Nature, volume 440, number 7082, pages 297-302, 2006. 5. Anton Kuzyk, Bernard Yurke, J. Jussi Toppari, Veikko Linko, and Pivi Trm,"Dielectrophoretic Trapping of DNA Origami", SMALL, volume 4, number 4, pages 447-450, 2008. 6. James C. Mitchell, J. Robin Harris, Jonathan Malo, Jonathan Bath, and Andrew J. Turberfield,"Self-Assembly of Chiral DNA Nanotubes", Journal of the American Chemical Society, volume 126, number 50, pages 16342-16343, 2004. 7. Faisal A. Aldaye, Alison L. Palmer, and Hanadi F. Sleiman,"Assembling Materials with DNA as the Guide", Science, volume 321, number 5897, pages 1795-1799, 2008. 8. Ebbe S. Andersen, Mingdong Dong, Morten M. Nielsen, Kasper Jahn, Ramesh Subramani, Wael Mamdouh, Monika M. Golas, Bjoern Sander, Holger Stark, Cristiano L. P. Oliveira, Jan Skov Pedersen, Victoria Birkedal, Flemming Besenbacher, Kurt V. Gothelf, and Jrgen Kjems,"Self-assembly of a nanoscale DNA box with a controllable lid", Nature, volume 459, pages 73-76, 2009. 9. Rahul Chhabra, Jaswinder Sharma, Yonggang Ke, Yan Liu, Sherri Rinker, Stuart Lindsay, and Hao Yan,"Spatially Addressable Multiprotein Nanoarrays Templated by Aptamer-Tagged DNA Nanoarchitectures", Journal of the American Chemical Society, volume 129, number 34, pages 10304-10305, 2007. 10. Nadrian C. Seeman,"An Overview of Structural DNA Nanotechnology", Molecular Biotechnology, volume 37, number 3, pages 246-257, 2007. 11. W. Shen, H. Zhong, D. Neff, M. L. Norton,"NTA directed protein nanopatterning on DNA Origami nanoconstructs", Journal of the American Chemical Society, volume 131, number 19, pages 6660-6661, 2009. 12. Constantin Pistol and Chris Dwyer,"Scalable, low-cost, hierarchical assembly of programmable DNA nanostructures", Nanotechnology, volume 18, number 12, pages 125305/1-125305/4, 2007.

OBJECTIVE: To design, fabricate, and demonstrate a new class of plasmonic sensors for chemical and biological sensing based on terahertz (THz) frequency quasi-optical spectroscopy. DESCRIPTION: The Army has an urgent need for new sensor-based plasmonic architectures for biological and chemical sensing, with superior sensitivity and high-volume processing capability. Examples include a novel nano-biosensor system comprising plasmonic emitters, waveguides, and detectors which can be integrated with other nanoelectronic circuit elements and components, such as switches and modulators, thereby resulting in enormous signal functionality, integration and processing speed. Recent development on metallic nanoparticles (MNPs), metallic nanoshells (MNSs) and metallic nanowires (MNWs) seemed promising, because the plasmonic nano-architectures provide a promising way to integrate with optical-electronic (including long wavelength THz regime) devices by localizing the light at a subwavelength scale [1-5]. Toward that end, THz signal transducers using the metallic metamaterial---because surface plasmon polariton (SPP) modes generate the weakly localized mode confinement in the THz domain---will need to be developed to fully realize the potential of the new class of THz plasmonic sensors. Specifically, it may be necessary to build holes, grooves, dimples, and other surface textures at the subwavelength scale, thus creating the spoof surface plasmon polariton (SSPP) modes similar to surface plasmon polariton (SPP) existing at the IR-Optical spectrum [6,7]. For example, various THz transducers such as waveguides, multiplexers and Mach-Zender interferometers using the sub-wavelength periodic gap structures need to be developed. Additionally, to improve the signal to noise figure of merit, it may be necessary to employ metallic photonic crystal materials consisting of cavities. It is also possible that the signal detection emitted by nanometer-scale atoms and molecules would be enhanced by strong near field confinement and extraordinary transmission of the plasmonic architectures. The artificially designed metallic photonic crystal slabs comprising of cavities with high Q-factor and small effective volume will make it possible to obtain ultrahigh sensitivity for chem.-/biosensor devices. Plasmonic waveguide structures such as slot waveguides, when combined with plasmonic switches, can deliver optical (THz) excitations to spectroscopy-based sensor arrays, and collect optical (THz) spectral information from these array elements, and subsequently direct them to desired output terminals. With such a design paradigm, the optical/THz plasmonic sensors"high sensitivity is accentuated, and at the same time, large throughput of sensory processing information is made possible. The ultimate goal of this project is to define a new class of THz plasmonic nanostructures which are highly effective for spectroscopy-based sensing and that are scalable and reproducible. Namely, when produced by available standard nanomanufacturing techniques required for realizing large sensor arrays, excited and interrogated by large number of plasmonic waveguide channels connected to the optical/THz input/output, uniform response properties will be exhibited by these sensors systems. PHASE I: In the Phase I effort, a complete design of a chem./biosensor based on the THz plasmonic nanostructures should be formulated, and the fabrication procedures should be developed for a representative device implementation. It is expected that physical attributes such as the plasmon resonance frequencies and local field enhancements will be predicted as a function of the geometric and material parameters of the plasmonic nanostructures. The Phase I effort should include fabrication experiments and benchmarking that demonstrate an adequate capability for the meeting the expected challenges in fabricating the proposed sensors. PHASE II: In the Phase II effort, a prototypical sensor array based on THz plasmonic nanostructured architecture, with plasmonic waveguides connected to the input/output optical/THz excitation and spectral collection/determination, will be fabricated and their ultrahigh detection sensitivity should be demonstrated. The performances of the THz plasmonic sensor array should be fully evaluated in terms of processing speed and amount of information processed. Although the THz plasmonic sensor array will be designed to be functional at one specific laser wavelength, the project needs to deliver theoretical/experimental results that provide guidance regarding how the sensor array can be designed and fabricated for other excitation wavelengths and possibly broad-band/sweep-frequency operations. PHASE III DUAL USE APPLICATIONS: The Phase III work will demonstrate scalability and repeatability of the proposed THz plasmonic nanostructured spectroscopy-based sensor arrays with ultrahigh sensitivity, and implement at least one kind of sensor featuring monolithic integration of the signal source and detector(s). Specifically, arrays of the proposed THz plasmonic nanostructures will be fabricated using standard nanofabrication technologies such as nanoimprint lithography or other scalable nanomanufacturing techniques. This new technology will have commercialization opportunities for such military relevant applications as detection of trace amount chemical, biological and explosive agents. This same technology would find dual-applications such as advanced laboratory components for scientific characterization studies; materials/process monitoring in commercial manufacturing; and ultra-fast data processing. REFERENCES: 1. H.A. Atwater,"The Promise of Plasmonics", Scientific American, April 2007; 56-63. 2. E. Betzig, J. K. Trautman, T. D. Harris, J. S. Weiner, and R. L. Kostelak,"Breaking the diffraction barrier optical microscopy on a nanometric scale", Science, 251, 1468 (1991). 3. W. L. Barnes, A. Dereux, and T. W. Ebbesen,"Surface plasmon subwavelength optics,"Nature, 424, 824 (2003). 4. K. Song and P. Mazumder,"Active Terahertz Spoof Surface Plasmon Polariton Switch Comprising the Perfect Conductor Metamaterial", IEEE Transaction on Electron Devices, 56, 2792 (2009). 5. M. L. Brongersma, J. W. Hartman, and H. A. Atwater,"Electromagnetic energy transfer and switching in nanoparticle chain arrays below the diffraction limit,"Physical Review B, 62, R16356 (2000). 6. J. B. Pendry, L. Martin-Moreno, and F. J. Garcia-Vidal,"Mimicking Surface Plasmons with Structured Surfaces,"Science, 305, 847 (2004). 7. S. A. Maier, S. R. Andrews, L. Martin-Moreno, and F. J. Garcia-Vidal,"Terahertz surface plasmon-polariton propagation and focusing on periodically corrugated metal wires,"Physical Review Letters, 97, 176805 (2006).

OBJECTIVE: Determine the effect on engine performance of introducing hydrogen/syngas into a compression ignition engine and develop a means to produce the hydrogen/syngas in-situ. DESCRIPTION: The Army seeks to improve the fuel efficiency and/or emissions of its compression ignition engines. Compression ignitions engines are utilized across a variety of platforms including, but not limited to, generator sets and vehicles. Research indicates that the dual fuel use of diesel and hydrogen/syngas (carbon monoxide and hydrogen) can improve combustion in compression ignition engines (1,2,3). Recent research and development in the area of catalytic fuel reformers, plasma reformers and other similar devices, indicates that a hydrogen rich stream (or syngas stream) can be produced efficiently from JP-8 in a compact on-board configuration (4,5,6). It has been postulated that hydrogen influences the combustion flame speed allowing for faster combustion at higher peak pressures which results in improved thermal efficiency (7). Thermal efficiency improvements of up to 28 percent have been reported with hydrogen addition8. Additionally, improvements in emissions in terms of NOx, particulate matter, carbon monoxide and smoke have also been reported (1,2,3). Because the addition of hydrogen/syngas appears to greatly improve combustion efficiency, this combustion technique may allow for broader fuel considerations to include renewable biomass based fuels, hydrogenation-derived renewable diesel fuels, and other future postulated synthetic middle distillate fuels. Thus far published research on this topic is limited and the engine performance effects are not always consistent9. This research could have broad implications across military mobility platforms, auxiliary power units and engine driven generators. For military purposes, generation of a hydrogen rich stream on demand via fuel reforming or other means is preferable to carrying hydrogen canisters. When fuel is reformed it is broken down primarily into H2 and CO, also known as syngas. The production of syngas in small quantities via fuel reforming should result in a compact reactor with negligible parasitic energy demands. Results from this research and development program should conclusively address the impact of the use of dual use JP-8/hydrogen fuels (or syngas) in a compression ignition engine through experimental results and design studies resulting in a laboratory demonstration unit and/or research engine test stand that can be delivered to the Government for performance verification. PHASE I: Through experimentation determine the effects of mixing hydrogen and/or syngas with JP-8 on combustion thermal efficiency and emissions. Based on preliminary results, postulate a conceptual design for a fuel reformer or other means to generate in-situ hydrogen and assess system level impacts such as performance, size, weight, safety, scaling and cost. PHASE II: Continue to fully map out engine performance with dual JP-8/hydrogen fuels determining engine operating conditions which result in best performance improvements. Experimentation and testing should also consider engine performance with renewable diesel and jet fuels. Design and fabricate a laboratory demonstrator unit consisting of a compression ignition engine, hydrogen or syngas generator device and means to load the engine. The purpose of the demonstrator unit/test bed is to allow the Government to independently verify performance. PHASE III DUAL USE APPLICATIONS: Conduct design studies to optimize the hydrogen/syngas generator device and diesel engine. Demonstrate physical integration and thermal integration through laboratory demonstrator design, fabrication and test. Compression ignition engines are used in a very broad array of commercial and military applications such as, primary vehicle propulsion, continuous and backup electric power generation, and as prime movers (engine driven compressors, pumps, etc.). Current and future commercial design emphasis is on improving efficiency and reducing emission; this topic specifically addresses these critical technology areas. REFERENCES: 1. Saravanan N, Nagarajan G. Experimental investigation in optimizing the hydrogen fuel on a hydrogen diesel dual-fuel engine. Energy Fuel 2009, 23, 2646-2657. 2. Ramirez-Lancheros R, Darmon A, Moreac G. Simulated impact of the addition of reformate on n-heptane oxidation under engine conditions. Proceeding of the European Combustion Meeting, 2009. 3. Antunes JMG, Mikalsen R, Roskilly AP. An experimental study of a direct injection compression ignition hydrogen engine. Int J Hydrogen Energy 2009, 34, 6516-6522. 4. Zheng J, Song C. Reforming of Liquid Hydrocarbon Fuels for Micro Fuel Cells. Steam Reforming of Pre-reformate from Jet Fuel over Supported Metal Catalysts. American Chemical Society, Fuel Chemistry Division 2003, 48(1), 378. 5. Jubaedi C, Vilekar S, Morgan C, Walsh D, Mastanduno R. ATR Developments for Reformation of Logistis Fuels. 44th Power Sources Conference, 14-17 June 2010, 509-511. 6. Elangovan S, Hartvigsen J, Czernichowski P, Czernichowski A. Sulfur Tolerant Liquid Fuel Reformer. SECA Core Technology Program Workshop, Session: Balance of Platn. Lakewood, CO, October 27, 2005. 7. Bari S, Esmaeil MM. Effect of H2/O2 addition ion increasing the thermal efficiency of a diesel engine. Fuel 2010, 89, 378-383. 8. Saravanan N, Nagarajan G. An experimental investigation of hydrogen-enriched air induction in a diesel engine system. Int J Hydrogen Energy 2009, 33, 1769-1775. 9. Avadhanula VK, Lin C, Witmer D, Schmid J, Kandulapati P. Experimental study of the performance of a stationary diesel engine generator with hydrogen supplementation. Energy Fuel 2009, 23, 5062-5072.

OBJECTIVE: We are seeking advanced, robust wavelength tuners for laser transmitters operating in the 3-5 um and 8-12 um bands for application to point and standoff detection of chemical and biological agents. DESCRIPTION: A variety of wavelength agile laser transmitters are contemplated for advanced point and standoff sensors to probe for chemical and biological agents. These include most notably Quantum Cascade Lasers (QCLs), CO2 TEA (Transverse Electric Atmospheric) lasers, CO2 waveguide lasers, and solid state lasers with optical parametric oscillators (OPOs). The CO2 types operate at moderate to high peak or average power and typically use precision rotating gratings to achieve wavelength selection. They can also be wavelength shifted by OPO, but in that case output power is limited by optical damage on the nonlinear crystal surfaces and shifter resonator optics. QCLs can be wavelength shifted by thermal means, but such lasers operating in Fabry-Perot resonators with angle tuned gratings can offer broader band coverage at high speed. Solid state lasers have proven to be most effective in the MWIR, although attempts have been made to extend their reach to the LWIR. In both these bands, angle tuned OPO shifters have been effective. In all these cases, one of the critical elements of the wavelength shifter is the precision angle tuning mechanism which must satisfy the combined requirements of speed, position accuracy and repeatability, compactness, and robustness. One example is the CO2 TEA laser now incorporated in the FAL (Frequency Agile Laser) which operates at a pulse repetition frequency (PRF) of 200 Hz. The FAL grating angle tuner requires a 10 rad angular resolution over a 5 degree angle with a settling time of 5 msec and an angular repeatability of 10 rad over temperature ranges of at least 0-40oC. The present FAL tuner achieves only a 2.5 degree of angle in 5 msec. Therefore, a two-fold increase in speed is required to solve the present requirement; and a speed increase of three to four times over the present device will be required to satisfy the advanced requirement for a higher data rate FAL system. Proposed improvements to the FAL laser transmitter to make more laser lines available by using isotope gas mixtures would require a two-fold improvement in the angular resolution and repeatability due to the increased selectivity required. The CO2 waveguide laser typically operates at tens of kHz PRF; however in that case, high number multiple pulse averaging is typical, and broadband wavelength shift rates on the order of 200-500 Hz are still applicable. The QCL type offers the advantage of small size even after the necessary thermal controllers and power supplies are added to the transmitter volume. In order to realize the small size potential of these relatively compact transmitters, an equivalently small tuner would be very desirable. Importantly, a small tuner would allow for efficient close coupling to the external Fabry-Perot resonator. Present tuners have volumes typically on the order of 600 cc, not including power supplies and ancillary electronics. What is needed is a reduction in tuner volume by at least 50% while achieving the speed and position accuracy required for an external resonator QCL. It is also very desirable to develop a tuner that is lightweight and electrically efficient so that the overall package size and weight can be kept below 2 liters and 1 kg, respectively. Wavelength tuning speed and precision are key to acquiring high fidelity target data upon which advanced detection algorithms can operate. For example, in the case of LWIR standoff detection, atmospheric and target evolution effects can induce significant data noise which can be alleviated to some extent by high laser PRF and wavelength tuning speed. High data speeds provide for the possibility of fast and effective pulse averaging leading to fast algorithm throughputs and reduced time to alarm. PHASE I: Perform analysis and feasibility studies. Develop conceptual designs for the tuner including a means to test and verify the performance. Provide a detailed development plan for design, fabrication, and testing of the wavelength tuner to be carried out in the Phase II program. PHASE II: Use the results of Phase I to design, fabricate, test and deliver a tuner prototype for demonstration with a government-furnished laser. Provide a roadmap for the integration of the laser and tuner combination with a government-furnished sensor. PHASE III DUAL USE APPLICATIONS: The result of Phase II will be demonstration of a tuner that can be used for rapidly interrogating chem-bio agents. In addition to immediate military applications, the tuner will find widespread use in important civilian applications, including WMD (weapons of mass destruction) detection, pollution monitoring, commercial manufacturing process monitoring, and commercial equipment that is necessary for scientific and aerospace corporations. REFERENCES: (1.) D. Cohn, W. Griffin, L. Klaras, E. Griffin, H. Marciniak, J. Fox, C. Swim,"WILDCAT sensor", SPIE Proceedings 4036, 210, Orlando, Florida, 24-25 (April 2000); (2.) D. Cohn, L. Klaras, J. Fox, C. Swim,"WILDCAT sensor design", Proceedings Fourth Joint Workshop on Standoff Detection for Chemical and Biological Defense, Williamsburg, VA, 305, 26-30 (Oct 1998); (3.) D. Cohn, J. Fox and C. Swim,"Frequency agile CO2 laser for chemical sensing", SPIE Proceedings, Los Angeles, California, vol. 2118, p 72, (Jan 1994).

OBJECTIVE: To develop a bioaerosol trigger based on electrostatic charge/discharge rates. DESCRIPTION: The current generation of UV fluorescence based triggers for bioweapon detection systems are not able to detect the complete spectrum of anticipated bioweapon attacks. Current biological warfare agent detection systems within the chem/bio defense community depend on UV fluorescence to trigger a detection event. Most biological agents possess a strong fluorescence signature that can be utilized both as a trigger and as a detection mechanism. Once the BW agent aerosol enters a sensor and triggers the device with an appropriate fluorescence signature, a series of confirming tests are performed to determine the presence or absence of a BW threat. Non-fluorescent BW threats, however, pose a problem. Without an appropriate trigger, confirming tests are not performed. Thus false negative responses can occur and may place personnel at risk. For non-fluorescent threats other properties must be utilized to develop a working trigger. A trigger technology that can better detect non-fluorescent threats is urgently needed. A promising solution to this important problem is a trigger based on the electronic charging physics of aerosol particles. Previous work has shown that aerosol particles exposed to an ionization source gain charge based on its material properties. Evidence of charging events or changes in aerosol charge could be used as a trigger in a bioaerosol detection system. Charging methods could potentially include corona discharge, charged air ions, UV, X-rays, gamma rays, electron beams, and beta particles. To facilitate the development of a bioaerosol trigger, aerosol charge signatures must be determined and the characteristic signatures of bioweapons identified. Previous experiments on the charging of smoke and soot particles have shown that aerosol particles can be charged by ionizing UV light. The UV photons were found to knock electrons off the surface of the aerosol particles in a manifestation of the photoelectric effect. The amount of charge developed was found to be a function of the material properties. Additionally, many charging process rates depend on a material"s electric permittivity. These and other charging effects could be combined or isolated to detect the presence of spores. Little is known about the charging and discharging process for biological spores. However, preliminary experiments have shown that the charge/discharge rates for airborne microorganisms could be significantly different than the charge/discharge rates of common airborne aerosols such as dust and smoke. An accurate experimental technique is required to catalogue the charge/discharge characteristics of spores and common interferants, as well as to anchor models. Physics based models are needed to support the experiment by predicting charge/discharge rates as well as to extrapolate experimental results to the design of a trigger system. PHASE I: Develop concepts for a diagnostic system to accurately measure the charging/discharging process of biological spores and common atmospheric aerosols. Develop a model that simulates the expected rate of particle charge and discharge for the same set of aerosols. Demonstrate the system"s feasibility through experiments or detailed analysis. Estimate the error level of the data collected with the system. PHASE II: Build a charge/discharge diagnostic system, and verify its operation. Build a database of charge/discharge rates for common atmospheric aerosols, as well as aerosolized bacterial spores. Determine rates for particles alone and in mixtures with other particle types. Confirm model predictions for charge/discharge rates with the experimental data. Analyze the database of charge/discharge rates and enumerate patterns that could be used to detect aerosolized bacterial spores. Determine the ability of the system to detect aerosolized bacterial spores in the presence of common airborne contaminants such as dust and smoke. PHASE III DUAL USE APPLICATIONS: Further research and development during Phase III efforts will be directed towards refining a final deployable design, incorporating design modifications based on results from tests conducted during Phase II, and improving engineering/form-factors, equipment hardening, and manufacturability designs to meet U.S. Army CONOPS and end-user requirements. An inexpensive system that can monitor for bioaerosols suspended in air has numerous commercial applications. REFERENCES: 1. K.R.S. Prier, B. Lighthart, and J. J. Bromenshenk,"Adsorption Model of Aerosolized Bacterial Spores (Bacillus subtilis Variety niger) onto Free-Flying Honey Bees (Hymenoptera: Apidae) and its Validation", Environmental Entomology, volume 30, issue 6, pages 11881194, 2001. 2. H. Burtscher, L. Scherrer, H. C. Siegmann, A. Schmidt-Ott, and B. Federer,"Probing Aerosols by Photoelectric Charging", Journal of Applied Physics, volume 53, issue 5, pages 3787-3791, 1982. 3. H. Burtscher,"Measurement and characteristics of combustion aerosols with special consideration of photoelectric charging and charging by flame ions", Journal of Aerosol Science, volume 23, number 6, pages 549-595, 1992. 4. A. Schmidt-Ott, P. Schurtenberger, and H. C. Siegmann,"Enormous Yield of Photoelectrons from Small Particles", Physical Review Letters, volume 45, pages 1284-1287, 1980. 5. W. J. Borucki, R. C. Whitten, E. L. O. Bakes, E. Barth, and S. Tripathi,"Predictions of the electrical conductivity and charging of the aerosols in Titan's atmosphere", Icarus, volume 181, issue 2, pages 527-544, 2006. 6. Christopher J. Hogan, Myong-Hwa Lee, and Pratim Biswas,"Capture of Viral Particles in Soft X-Ray-Enhanced Corona Systems: Charge Distribution and Transport Characteristics", Aerosol Science and Technology, volume 38, issue 5, pages 475-486. 2004. 7. Jingkun Jiang, Myong-Hwa Lee, and Pratim Biswas,"Model for nanoparticle charging by diffusion, direct photoionization, and thermionization mechanisms", Journal of Electrostatics, volume 65, issue 4, pages 209-220, 2007. 8. Arkadi Maisels, Frank Jordan, and Heinz Fissan,"Dynamics of the aerosol particle photocharging process", Journal of Applied Physics, volume 91, issue 5, pages 3377-3383, 2002. 9. R. Niessner and G. Walendzik,"The Photoelectric Aerosol Sensor as a Fast-Responding and Sensitive Detection System for Cigarette Smoke Analysis". Fresenius Zeitschrift fur Analytische Chemie, volume 333, pages129-133, 1989. 10. Eric M. Kettleson, Bala Ramaswami, Christopher J. Hogan, Jr., Myong-Hwa Lee, Gennadiy, A. Statyukha, Pratim Biswas, and Largus T. Angenent,"Airborne Virus Capture and Inactivation by an Electrostatic Particle Collector", Environmental Science & Technology, volume 43, number 15, pages 5940-5946, 2009. 11. Arkadi Maisels, Frank Jordan, Frank Einar Kruis and Heinz Fissan,"A Study of Nanoparticle Aerosol Charging by Monte Carlo Simulations", Journal of Nanoparticle Research, volume 5, numbers 3-4, pages 225-235, 2003.

OBJECTIVE: To develop an alternative to the existing hexachloroethane (HC) and terephthalic (TA) smoke compositions that will produce a very low flame while maintaining a high smoke output. This composition should be similar in high performance as the M8 HC Smoke Grenade but with much less toxic materials and less incendiary hazards. New formulations should avoid hazardous materials to address toxicological concerns. HC smoke grenades produces toxic products such as zinc chloride. Some flame reductions could be achieved through hardware design, but improved chemical compositions are desirable. These devices intended for hand held devices to protect personnel, specifically the M8, but can also find use in the vehicle launched M83 grenade as well. Desirable specifications of the M8: provide a screen 3 meters high by 10 meters long; build up a cloud within 6 seconds,; having a duration of at least 90 seconds. Current TA smoke is a much less toxic and less incendiary smoke but is much lower in performance than the M8 HC smoke. DESCRIPTION: Currently visible obscurant grenades employ high explosives configured as a center burster to disseminate spherical powders. These devices offer very short dissemination periods, making it difficult to maintain protection for the soldier and equipment. Pyrotechnic smokes are composed of active fillers that typically consist of HC smoke mixtures (hexachloroethane/zinc) or TA smoke mixtures (terephthalic acid). In addition, Red Phosphorus is widely used to generate long duration visible obscuration. For all pyrotechnic or burning devices, there are many flame hazards associated with them that restrict their use. These items are avoided because they start brush fires in outdoor applications. They are very difficult to use for indoor applications and create hazards for personnel. The following is a list of performance metrics of various visible smoke grenades. 1. Red Phosphorous (RP) Yield factor of 4.8 at 10 degrees C, 50% RH. Extinction () is 3.5m2/g, Pack Density 2.0, FOM=21 2. Hexachloroethane (HC) Yield factor is 2.1 at 10 degrees C, 50% RH. Extinction () is 3.9m2/g, Pack Density 1.9, FOM=7.4 3. Terephthalic (TA) Yield factor is 0.28 at 10 degrees C, 50% RH. Extinction () is 4.9m2/g, Pack Density 1.3, FOM=3.4 PHASE I: Develop alternative formulations that when reacted, produce a yield factor of at least 2.0. Yield factor is the amount of grams airborne divided by the total amount of grams disseminate. New formulations should also have material extinctions of at least 3.5m2/g in the visible wavelength region. Flame fronts reduction should be at least 50% the HC M8 grenade, which is generally around 1ft at initiation. Ideally, no flame fronts are desired. Demonstrate a concept that can produce a similar amount of smoke as the M8 without using HC that can give Grenade Figure of Merit (FOM) of about 4.0. The FOM for a grenade would be the product of the extinction value, fill fraction, packing density and yield. One possible solution would be to produce hydroscopic species that can increase yield factors(FY). Improving the YF of the current TA smoke grenades (M83 and M90) from approximately 0.28 (or 28%) to something closer to the HC grenades will increase the Grenade Figure of Merit (FOM). Improvement in the how to fill and pack devices will improve the fill fraction and packing densities. New formulations should have higher than 4.0 extinction coefficients (with a high scattering component) in the visible region and be less toxic than the current M8 HC Smoke Grenade. Edgewood Chemical Biological Command (ECBC) has already focused on the ability to obtain a suitable reactions from the embedded chlorine with environmentally friendly oxidizers, as well as looked at finding other suitable fuels to replace the zinc in the old HC smoke composition. Tests can be performed at ECBC obscurant chamber to determine dissemination efficiency, extinction values, temperature and burn rates. At least 5 devices with different formulations should be delivered to ECBC for testing at the end of Phase I Toxicology is a complex and expensive field to evaluate. For Phase 1, a literature search should be provided to compare any new formulation to the existing HC formulation. In reference 6, the 15 minute exposure for HC smoke is given as 10mg/m3. PHASE II: Down select from the Phase I effort at least two formulations that show improvements in the grenade figure of merit and reductions in flame fronts on the M8 size device. Refine the design into two fully-functioning grenades. These must have the overall dimensions of the M106 or M8 handheld grenade. The second part of the Phase II effort is to design and produce using the previous formulations a larger size device with the overall dimensions of the M90 vehicle launched grenade. Scale up includes both hardware design and generation of material. An analysis of how the increase container size and material fills will effect the smoke production and dispersion. Finally, scale up production of the fill material and grenade hardware to be able to field test 60 (30 of each M8 and M90 size) devices at ECBC outdoor field testing areas to demonstrate improvements in smoke production (FOM) and flame reduction. PHASE III DUAL USE APPLICATIONS: The grenades developed in this program can be integrated into current military obscurant applications. Improved visual devices are needed to reduce current logistics burden in needing to carry countermeasures to protect the soldier and his equipment. Other dual use applications include markers for emergency rescue, signaling operations and aeronautic stunt planes. Improved dissemination techniques can be beneficial for all powdered materials in the metallurgy, ceramic, pharmaceutical and fuel industries. Industrial applications include electronics, fuel cells/ batteries, and solar energy. REFERENCES: 1. Bohren, C.F.; Huffman, D.R. Absorption and Scattering of Light by Small Particles; Wiley-Interscience: New York, 1983. 2. Embury, Janon; Maximizing Infrared Extinction Coefficients for Metal Discs, Rods, and Spheres, ECBC-TR-226, Feb 2002, ADA400404, 77 Page(s) 3. Clyens, S.; Johnson, W., The Dynamic Compaction of Powdered Materials, Materials Science and Engineering, 30 (1977), 121-139. 4. Schwarz, R. B., Kasiraj, P., Vreeland T., Ahrens, T. J., A Theory for the Shock-wave Consolidation of Powders, Acta Metall., Vol. 32, pp. 1243-1252. 5. Pyrotechnic Smoke Analysis Vol I, ERDEC-TR-129, N. Sordoni, W.Heard, W. Rouse, Dec 1993 6. Toxicity of Military Smokes and Obscurants, Vol 1, Committee on Toxicology, Commission on Life Sciences, National Research Council., ISBN 0-3090-56 166-3

OBJECTIVE: Design, fabrication, and demonstration of an electrophoretic capillary nanofluidic integrated sensor platform effective for the separation of biological molecules into different sizes for use in detection, identification, and classification applications. DESCRIPTION: Recently methods have been developed to rapidly separate long-strand polymers according to length. The separation mechanism utilizes confinement-induced forces to separate the polymers into different size fractions. Researchers have examined interfaces between regions of vastly different configuration entropy, where small fragments can become trapped in favorable regions, but the larger fragments cannot completely enter due to the large size. Researchers have also examined mechanical and/or field-induced dielectrophoretic DNA trapping due to the surface roughness within nanopores and selective binding of nucleic acids to silica particles. Nanofluidic separators hold the promise for rapid, inexpensive separation of DNA strands and other polymers into fractions that are characterized by different polymer strand lengths. However, the work has been hampered by a complete understanding of the transport behavior of long and short DNA strands in nanochannels. This topic seeks to address transport phenomena in micro and nano channels with the goal of building better separation devices. PHASE I: Examine the transport behavior of long and short DNA strands in fused silica nanochannels with the application of electrical fields of different strengths. Examine mechanical and/or field-induced dielectrophoretic DNA trapping due to the surface roughness within the nanochannels. Examine areas within the nanofluidic channels with induced interfaces between regions of vastly different configuration entropy. Examine methods for utilizing DNA transport in nanochannels as a method for separating the DNA into fractions of differing length. PHASE II: The Phase II effort of the program should build and test a functioning nanofluidic separation platform. The research and development work should include an assessment of the prototype"s ability to separate relevant bio-materials and/or bio-agent targets into fractions according to length. The prototype nanofluidic sensor platform should be packaged in a form factor that readily interfaces with spectroscopy systems. The separation system should allow for stand-alone operation with fluidic and electrophoretic control that is self-sustained to facilitate a transparent operation by the user. PHASE III DUAL USE APPLICATIONS: Further research and development during Phase III efforts will be directed towards refining a final deployable design, incorporating design modifications based on results from tests conducted during Phase II, and improving engineering/form-factors, equipment hardening, and manufacturability designs to meet U.S. Army CONOPS and end-user requirements. Specifically improved nanofluidic separation will have relevance to scientific studies on biological materials and structures, to the detection and identification of biological threats, to medical diagnostics of biological induced diseases, to the monitoring of commercial consumables for biological contamination, just to name a few possibilities. REFERENCES: 1. Mario Cabodi, Stephen W. P. Turner, and Harold G. Craighead,"Entropic Recoil Separation of Long DNA Molecules", Analytical Chemistry, volume 74, number 20, pages 51695174, 2002. 2. Stephen L. Levy, John T. Mannion, Ji Cheng, Christian H. Reccius, and Harold G. Craighead,"Entropic Unfolding of DNA Molecules in Nanofluidic Channels", Nano Letters, volume 8, number 11, pages 3839-3844, 2008. 3. Georgette B. Salieb-Beugelaar, Juliane Teapal, Jan van Nieuwkasteele, Danil Wijnperl, Jonas O. Tegenfeldt, Fred Lisdat, Albert van den Berg, and Jan C. T. Eijkel,"Field-Dependent DNA Mobility in 20 nm High Nanoslits", Nano Letters, volume 8, number 7, pages 1785-1790, 2008. 4. Jian Wen, Lindsay A. Legendre, Joan M. Bienvenue and James P. Landers,"Purification of Nucleic Acids in Microfluidic Devices", Analytical Chemistry, volume 80, issue 17, page 64726479, 2008. 5. Qirong Wu, Joan M. Bienvenue, Benjamin J. Hassan, Yien C. Kwok, Braden C. Giordano, Pamela M. Norris, James P. Landers, and Jerome P. Ferrance,"Microchip-Based Macroporous Silica Sol & #8722;Gel Monolith for Efficient Isolation of DNA from Clinical Samples", Analytical Chemistry, volume 78, number 16, pages 5704-5710, 2006. 6. A Bhattacharyya and C.M. Klapperich,"Thermoplastic microfluidic device for on-chip purification of nucleic acids for disposable diagnostics", Analytical Chemistry, volume 78, number 3, pages 788-792, 2006. 7. M. J. O'Brien, P. Bisong, L. K. Ista, E. M. Rabinovitch, A. L. Garcia, S. S. Sibbett, G. P. Lopez and S. R. J. Brueck,"Fabrication of an Integrated Nanofluidic Chip using Interferometric Lithography", Journal of Vacuum Science and Technology B, volume 21, pages 2941-2945, 2003.

OBJECTIVE: To develop a quantitatively accurate, physics-based model for predicting and interpreting infrared (IR) reflectance and emittance spectra of surfaces contaminated with liquids. Emphasis will be on modeling the reflectivity of irregular surfaces and surfaces composed of granular materials in the long wavelength infrared (LWIR, 800 to 1200 wavenumber) spectral region. DESCRIPTION: Detection of liquid contaminants on surfaces is a high priority within the Joint Service Chemical and Biological Defense community. New methods are required to protect DOD personnel from exposure to persistent chemical agents by providing early warning and mapping of contaminated areas. Standoff detection methods based on IR spectroscopy using both IR reflectance and emittance have shown promise in providing wide-area surveillance for contaminated areas; however, IR reflectance and emittance spectra are complex and not easy to analyze. A new suite of physics-based modeling tools will facilitate the development of the next generation of standoff sensor for detecting and mapping persistent agents on surfaces. The reflectivity of liquid-contaminated natural surfaces is generally not well described using simple reflectance models. Microscopic masking and shadowing effects are generally not accounted for in many models of surface reflectivity. It is typically necessary to treat natural surfaces as a collection of randomly-oriented facets in order to address masking and shadowing effects. Many natural surfaces are highly irregular, and incident light undergoes multiple reflections prior to exiting the medium. Effective models for granular media treat the material as a collection of particles with wavelength-dependent scattering albedos in order to address multiple scattering effects. Thin film models of LWIR surface reflectance generally presume a single reflection from a contiguous surface. For granular media, where particle sizes are comparable to the wavelength of incident light, and for solid surfaces which are rough on the length scale of the incident wavelength, diffraction effects are significant and need to be included in the reflectance model. For liquids which are well dispersed in the surface medium, the reflectivity of the contaminated medium may be better modeled in terms of a volumetrically-averaged refractive index rather than as discrete layers of materials with differing refractive indices. The appropriate model depends on the length scale of the internal surface roughness/particle size. PHASE I: Utilize modeling techniques to analyze IR reflectance and emittance data from thin layers of a non-volatile liquid simulant that have been applied to a variety of natural and man-made surfaces. Data analysis of the LWIR region will be emphasized. For this study, the stimulant will consist of a low-volatility silicon-based oil with strong absorption features in the 800 to 1200 wavenumber region. Surfaces should include dirt, sand, grass, concrete, and asphalt. Identify gaps in existing models and determine methods for improvement of existing models. PHASE II: Develop a physics-based model that can be used to predict the IR signature of a liquid stimulant on surfaces. The physics-based model should depend on the physical properties of the liquid contaminant, including complex index of refraction, vapor pressure, viscosity, etc. Design and build a computer program for prediction and automated data analysis of the spectral response of liquid contaminants on surfaces. Demonstrate ability to the new model to predict and analyze the IR signature of the simulant on a variety of surfaces. Using the physics-based model along with the known physical properties of persistent chemical agents, predict the spectral response of the liquid agents on a variety of surfaces and predict the utility of IR reflectance and emittance measurements as a method of detecting low-level contamination. PHASE III DUAL USE APPLICATIONS: Further research and development during Phase III efforts will be directed toward refining a final working model, incorporating modifications based on results from simulations and tests conducted during Phase II, and improving packaging and graphic interfaces to meet U.S. Army CONOPS and end-user requirements. The fundamental mathematical, computational, and statistical tools developed in this program will have broad impact across several avenues of defense applications. Examples include sensor, intelligence, biological, logistical, and other DOD-critical applications. Commercial applications of IR imaging include pollution monitoring and mineral exploration. REFERENCES: 1. K.E. Torrance and E.M. Sparrow,"Theory for Off-Specular Reflection From Roughened Surfaces", Journal of the Optical Society of America (JOSA), volume 57, number 9, pages 1105-1114 (1967). 2. R. L. Cook and K. E. Torrance,"A Reflectance Model for Computer Graphics", Computer Graphics, volume 15, number 3, pages 307-316 (1981). 3. X. D. He, K. E. Torrance, F. X. Sillion, and D. P. Greenberg,"A Comprehensive Physical Model for Light Reflection", Computer Graphics, volume 25, number 4, pages 175-186 (1991). 4. B. Hapke,"Bidirectional Reflectance Spectroscopy. 1. Theory", Journal of Geophysical Research, volume 86, pages 3029-3054 (1981). 5. B. Hapke and E. Wells,"Bidirectional Reflectance Spectroscopy. 2. Experiments and Observations", Journal of Geophysical Research, volume 86, pages 3055-3060 (1981). 6. B. Hapke,"Bidirectional Reflectance Spectroscopy. 3. Correction for Macroscopic Roughness", Icarus, volume 59, pages 41-59 (1984). 7. B. Hapke,"Bidirectional Reflectance Spectroscopy. 4. The Extinction Coefficient and the Opposition Effect", Icarus, volume 67, pages 264-280 (1986). 8. B. Hapke,"Bidirectional Reflectance Spectroscopy. 5. The Coherent Backscatter Opposition Effect and Anisotropic Scattering", Icarus, volume 157, pages 523-534 (2002). 9. L. T. Maloney,"Evaluation of linear models of surface spectral reflectance with small numbers of parameters", Journal of the Optical Society of America A (JOSA A), volume 3, number 10, pages 1673-1683 (1986). 10. D. P. Roy, P. E. Lewis, and C. O. Justice,"Burned area mapping using multi-temporal moderate spatial resolution data - A bi-directional reflectance model-based expectation approach", Remote Sensing of Environment, volume 83, number 1-2, pages 263-286 (2002). 11. S. K. Nayar, K. Ikeuchi, and T. Kanade,"Surface reflection: physical and geometrical perspectives", IEEE Transactions on Pattern Analysis and Machine Intelligence, volume 13, issue 7, pages 611-634 (1991). 12. L.B. Wolff and T.E. Boult,"Constraining Object Features Using a Polarization Reflectance Model", IEEE Transactions on Pattern Analysis and Machine Intelligence, volume 13, number 7, pages 635-657 (1991)

OBJECTIVE: Develop an innovative, minimally-invasive and efficient DNA vaccination delivery platform using nanotechnology DESCRIPTION: Endemic, emerging and genetically engineered pathogens pose great risk to deployed military personnel. Although vaccination is the single best means for preventing infectious diseases, conventional vaccine development methods, which require attenuation or inactivation of dangerous pathogens, are not amenable to the rapid development of novel vaccines or for production of multiagent vaccines. In contrast, DNA vaccines can be rapidly engineered, readily combined and present minimal safety risks. Despite these attributes, DNA vaccines face a number of challenges before they can realize their full potential. A key obstacle for mass vaccination with DNA is the absence of an effective and tolerable delivery method. Delivery has remained problematic because it is essential that the DNA enter host cells in order for it to generate immunogenic proteins. The most commonly used method of delivery, needle injection into muscles, results in poor immune responses because the DNA is deposited into intracellular spaces and is not efficiently taken up by the host cells. Other methods, which more effectively deliver the DNA to cells are still inadequate or are too invasive for general use. For example, gene gun delivery requires the DNA vaccines to be coated onto microscopic gold beads that are dispensed into skin cells by gas propulsion. Although this method results in deposition of the DNA directly into cells, only a very small quantity of DNA can be delivered at one time; thus, this method is not well-suited for delivering multiple DNA vaccines. Another method, intramuscular electroporation, involves injecting the DNA then quickly applying short electrical pulses to the delivery site. The electrical charge causes temporary pores to form in cellular membranes and facilitates uptake of the DNA vaccines. Electroporation has been found to greatly improve immune responses to DNA vaccines as compared to injection alone, and it allows for delivery of larger quantities of DNA in a single dose; however, intramuscular electroporation is more invasive and painful than is desirable for routine vaccination. In order to advance DNA vaccine technology, a novel and innovative delivery approach that is more tolerable, yet still effective is needed. Recent advances in nanotechnology provide one promising path toward efficient intracellular delivery of DNA vaccines. Several methods have been reported in the last few years for manufacturing stable nanoparticles that can incorporate biomaterials such as proteins or DNA. Because of their extremely small size and chemical composition, these particles are able to readily penetrate cells to deliver DNA to the cytoplasm or nucleus of cells. Further research and development is required to identify and manufacture safe, reproducible and stable nanoparticle-DNA vaccines that can be delivered in a minimally invasive manner to animal models, and ultimately to humans. The optimal vaccine platform would consist of nanoparticles containing sufficient DNA to elicit a desired immune response after minimally-invasive delivery. Further, the nanoparticle components should be acceptable for use in humans. A marginally successful outcome would provide nanoparticles containing DNA that are able to elicit superior immune responses as compared to those achieved with standard DNA vaccines delivered in solution by intramuscular injection. PHASE I: This Phase will demonstrate the feasibility of generating nanoparticles containing functional DNA vaccines using components suitable for human use. PHASE II: In this Phase, the nanoparticle vaccine platform developed in Phase 1 will be validated with DNA vaccines of interest to the military in an appropriate animal model. Immune responses to the vaccine of interest will be characterized. This phase will involve further refinement of the nanoparticle manufacturing technology, such that the nanoparticles can be demonstrated to be stable and consistent, and to be capable of delivering two or more DNA vaccines to skin using a minimally-invasive method. PHASE III DUAL USE APPLICATIONS: The resultant vaccine technology would be of value to both military and civilian populations for preventing infectious diseases. The technology would provide a means to administer several vaccines in a single dose, with low or no pain; thus, increasing tolerability and decreasing vaccination burden. Examples of vaccines that would be of dual use for civilian and military populations include: trivalent vaccines for Venezuelan, eastern and western equine encephalitis; bivalent vaccines for hemorrhagic fever with renal syndrome; quadravalent vaccines for Dengue hemorrhagic fever; and multigene vaccines for malaria. The technology would also provide both civilian and military populations with a path toward rapid response to unknown, emerging, or genetically engineered pathogens. Spin-off technologies would include further improvement in equipment and biologics required for manufacturing the DNA and nanoparticles. Transition to use in the military and to civilian populations would most likely involve acquisition of the technology by a large Pharmaceutical Company interested in producing commercially viable vaccines for civilian and military use. REFERENCES: 1. Caputo, A., Sparnacci, K., Ensoli, B., and Tondelli, L. (2008). Functional polymeric nano/microparticles for surface adsorption and delivery of protein and DNA vaccines. Curr Drug Deliv 5(4), 230-42. 2. Khatri, K., Goyal, A. K., and Vyas, S. P. (2008). Potential of nanocarriers in genetic immunization. Recent Pat Drug Deliv Formul 2(1), 68-82. 3. Masotti, A., and Ortaggi, G. (2009). Chitosan micro- and nanospheres: fabrication and applications for drug and DNA delivery. Mini Rev Med Chem 9(4), 463-9. 4. Scheerlinck, J. P., and Greenwood, D. L. (2008). Virus-sized vaccine delivery systems. Drug Discov Today 13(19-20), 882-7.

OBJECTIVE: Using a wound/repair animal model that is relevant to humans, elaborate the mechanism by which the various molecules involved in wound healing and repair (e.g. Polycomb Gene Group Proteins and associated demethylases) induce the repair transcriptome (including cell-cycle regulators, matrix molecules, integrins, proteases and antioxidant enzymes). Use the finding to develop diagnostic tests that assess the progress of wound repair and develop a plan for novel therapies that will enhance recovery. DESCRIPTION: Wound and tissue repair and restoration is of critical importance to the returning warfighter. Approaches to repair are actively being studied using stem cell biology and engineering. Epigenetic approaches have great potential but to date are not being actively investigated in the context of wound healing and repair. Epigenetics refers to changes in phenotype (appearance) or gene expression caused by mechanisms other than changes in the underlying DNA sequence, hence the name epi- (Greek: over; above) -genetics. These changes may or may not remain through cell divisions. However, there is no change in the underlying DNA sequence of the organism; instead, non-genetic factors cause the organism's genes to behave (or"express themselves") differently. The ability to direct the wounding/acute response/inflammatory/immune, repair and regenerative pathways following injury could provide a critical path in wound care for the individual at crucial time(s) in the process. Epigenetic changes can be induced in a number of ways. DNA methylation and post-translational modification of histones are the most widely studied examples. Additional small molecules can participate in epigenetic processes by covalent modification of histone proteins including acetylation, ubiquitylation, phophoylation, etc. The ability of small noncoding RNA molecules to induce epigenetic changes is also being increasingly studied. More recently, it has become clear that epigenetic mechanisms are used to respond to changes in the cell nucleus during development and more recently during wound healing and repair. Additional investigation into the molecular details of epigenetic changes during wound healing and repair may shed additional light on this process and inform us on ways to better treat the wounded warfighter immediately and during recuperation. PHASE I: Phase 1 would comprise the identification of small molecules that would initiate, propagate, or sustain repair and or resilience of particular cells or tissues following injury or during embryogenesis. Initial focus could be on the Polycomb Group Protein model to understand the various genes and proteins involved in the repair process, but does not have to be limited to this model. PHASE II: Phase II would identify candidate molecules that could be pursued in animal models. These molecules could be used as diagnostic tools to assess the quality of repair and developed in assays to evaluate therapeutic molecules. PHASE III DUAL USE APPLICATIONS: This phase would provide proof of principle in animal models including one non rodent species. This phase would involve a required pre-meeting with the FDA. REFERENCES: 1) Adrian Bird (2007). Perceptions of epigenetics. Nature 447: 396398 2) Ingela Djupedal and Karl Ekwall (2009) Epigenetics: heterochromatin meets RNAi. Cell Research 19:282-295. 3) Tanya Shaw and Paul Martin (2009). Epigenetic reprogramming during wound healing: loss of polycomb-mediated gene silencing may enable upregulation of repair genes. EMBO reports, 10 (8): 881-886

OBJECTIVE: Traumatic Brain Injury (TBI) is one of the hallmark injuries of the current conflicts in Iraq and Afghanistan. The primary source of these injuries is exposure to blast from Improvised Explosive Devices (IEDs). TBIs have a wide spectrum of sequelae associated with them. While severe TBIs are rapidly identifiable (many are skull penetrating), mild and moderate TBIs are much more difficult to detect and diagnose. Indeed, much of military medical research is devoted towards understanding these subtle injuries. Mild and moderate and TBIs are suspected in Post Traumatic Stress Disorder, seizures and even in Alzheimer"s disease and Parkinsonism. Diffusion Tensor Imaging is a subset of Magnetic Resonance Imaging (MRI) technology, which many Radiologists, Medical Physicists and Clinicians hypothesize could be a key tool towards unraveling the pathological nature of mild and moderate TBIs. One of the major challenges precluding this technique from wider acceptance as a tool for TBI detection and diagnosis is the lack of data acquisition and instrumentation standards between manufacturers and researchers. Standards or tools that could be used to calibrate measurements between operators and instrumentation would greatly increase our knowledge of TBIs. It would enable more direct comparisons between datasets acquired at differing medical institutions. It would also help to standardize long-term instrument performance at a given institution. This would reduce the amount of noise within single datasets and empower their standalone statistical significance. This topic seeks Research, Development, Test and Evaluation funds to develop MRI phantoms for DTI in order to provide a means of calibrating MRI scanner performance across multiple research facilities. This would greatly enable the meaningful analysis and sharing of complex TBI patient datasets. As a result, it would great help move the field towards imaging biomarkers for these injuries. DESCRIPTION: The human brain is perhaps the most complex information management and processing system ever created. It is also arguably one of the most fragile. Despite centuries of study, our understanding of how the structure of the brain is altered in response to the pathologies of disease and injury is still in its infancy. Traumatic Brain Injury (TBI) research is a high priority for today"s military since these injuries are often seen currently seen in theater. Many of these are the result of exposure to Improvised Explosive Devices (IEDs). High performance medical imaging techniques have enabled our understanding of diseases and pathologies such as stroke, multiple sclerosis and Parkinsonism (1-3). Techniques such as Computed Tomography (CT) and MRI also have been used to understand severe TBIs (4); however it has become clear that these conventional anatomical imaging methods in their current forms offer little towards understanding the full nature of mild and moderate TBIs. One novel technique currently under evaluation for its potential to evaluate mild and moderate TBIs is Diffusion Tensor Imaging (DTI), a subset of MRI. In DTI, the alterations in the microenvironments in brain, such as in neuronal fibers can be detected by changes in the diffusion properties of water. While Levin et al. (6) present evidence that DTI could be of limited use for mild and moderate TBIs, several other reports show that DTI offers the potential to identify imaging biomarkers of these injuries (7-8). A recently hosted DTI workshop identified some of the major bottlenecks towards improving the sensitivity and specificity of DTI (9). Improving the sensitivity and specificity was identified as a key component towards addressing the efficacy of this technique to identify injuries associated with mild and moderate TBIs. One strategy towards boosting the sensitivity and specificity of this technique is to acquire DTI-specific phantoms, which would be used to standardized instrumentation and acquisition parameters. This standardization is envisioned not only to be used across institutions; but as an internal standard across large patient cohorts acquired at a single site. The latter point is very important since dataset homogeneity is required to enhance any potential signal associated with very subtle differences in brain anatomy that may be attributable to mild or moderate TBI. MR scanner performance is well known to require occasional calibration. Secondly, standardization across multiple instruments and facilities will allow for sharing of datasets. This, in turn, would greatly increase the statistical power of these measurements. This topic therefore seeks the development of DTI phantoms for performance standardization of MR scanners. The ability to calibrate the performance of MR scanners to specifically perform DTI undoubtedly will reduce systematic errors associated with the acquisition of DTI datasets. PHASE I: The intent of this effort is to develop DTI phantoms that will mimic axonal integrity and water/dye diffusion through axons. Preliminary validation is expected at the end of Phase I. A validation plan should be presented as part of the proposal. The primary emphasis of the validation should pertain to the data acquisition chain in DTI rather than post processing. PHASE II: The selected proposal will outline a plan by which the prototype will be fully validated on a minimum of two different MRI scanners made by different manufacturers. The scanners used must be clinical scanners with data acquisition packages that are cleared for routine use by the FDA or local IRB. It is expected that as part of the validation process, the initial prototype will be refined. The validation plan should include a robust discussion of how improvements in data acquisition will be quantified. The end product of this development cycle is expected to generate a reproducible, complete phantom for DTI image acquisition standardization. The finished phantom prototype will be tested for a series of three reproductions of the prototype phantom. The selected proposal will outline a plan by which quality assurance for this low-scale initial production can be accomplished. It is expected that this plan will be similar to the original validation for the early prototype and will use multiple scanners of different manufacturer makes. PHASE III DUAL USE APPLICATIONS: In addition to improving our knowledge of combat-induced imaging biomarkers for mild and moderate TBI, other diseases such as Multiple Sclerosis and Parkinsonism would also benefit from the use of these phantoms. Standardizing the performance of MRI scanners for DTI could reveal subtle imaging-related clues regarding the onset of these diseases at their earliest stages. Phase III of this solicitation would therefore consider how these devices could advance our knowledge of imaging biomarkers for these diseases in a clinical setting. Other neuropathological diseases would be considered as well. The ultimate goal for this phase will be to validate a DTI imaging protocol for any proposed neurological or neuropathological insult that the offeror wishes to study outside of mild and moderate TBI. REFERENCES: (1) Ramli N, Rahmat K, Azmi K, Chong HT; The past, present and future of imaging in multiple sclerosis; J Clin Neurosci. 2010 Apr;17(4):422-7. Epub 2010 Feb 18. (2) Seppi K, Poewe W; Brain magnetic resonance imaging techniques in the diagnosis of parkinsonian syndromes. Neuroimaging Clin N Am. 2010 Feb;20(1):29-55. (3) Wardlaw JM; Neuroimaging in acute ischaemic stroke: insights into unanswered questions of pathophysiology; J Intern Med. 2010 Feb;267(2):172-90. (4) Jagoda AS, Bazarian JJ, Bruns JJ Jr, Cantrill SV, Gean AD, Howard PK, Ghajar J, Riggio S, Wright DW, Wears RL, Bakshy A, Burgess P, Wald MM, Whitson RR; Clinical policy: neuroimaging and decisionmaking in adult mild traumatic brain injury in the acute setting. J Emerg Nurs. 2009 Apr;35(2):e5-40. (5) Belanger HG, Vanderploeg RD, Curtiss G, Warden DL; Recent neuroimaging techniques in mild traumatic brain injury. J Neuropsychiatry Clin Neurosci. 2007 Winter;19(1):5-20. (6) Levin HS, Wilde E, Troyanskaya M, Petersen NJ, Scheibel R, Newsome M, Radaideh M, Wu T, Yallampalli R, Chu Z, Li X; Diffusion tensor imaging of mild to moderate blast-related traumatic brain injury and its sequelae. J Neurotrauma. 2010 Apr;27(4):683-94. (7) Hartikainen KM, Waljas M, Isoviita T, Dastidar P, Liimatainen S, Solbakk AK, Ogawa KH, Soimakallio S, Ylinen A, Ohman J; Persistent symptoms in mild to moderate traumatic brain injury associated with executive dysfunction. J Clin Exp Neuropsychol. 2010 Mar 1:1-8. (8) Kumar R, Gupta RK, Husain M, Chaudhry C, Srivastava A, Saksena S, Rathore RK; Comparative evaluation of corpus callosum DTI metrics in acute mild and moderate traumatic brain injury: its correlation with neuropsychometric tests. Brain Inj. 2009 Jul;23(7):675-85. (9) Diffusion MRI for TBI Roadmap Development Workshop. June 2-3, 2010, Omni Hotel, Chicago.

OBJECTIVE: The objective of this topic is to develop autonomous capability for robots with human-like dexterity to perform complex tasks for medical applications. DESCRIPTION: Current low-dimensional robots are directed by human operators using operator control units (OCUs) such as hand controllers that send a continuous stream of commands to the end-effector to follow a desired trajectory. This"teleoperation"control strategy places a significant cognitive load on the operator, which grows exponentially as the number of degrees of freedom (DOF) of the robot increases (Lane et al., 2001). For example, a humanoid robot such as the Battlefield Extraction and Assist Robot (BEAR) has over 20 degrees of freedom (Atwood and Klein, 2010), as opposed to the manipulator on a Talon or Packbot robot that has three DOFs (Yamauchi, 2004). NASA"s Robonaut is another example of complex robotic system that is difficult to teleoperate (Ambrose et al., 2000). Difficulties encountered in coordinating operations with the remotely operated vehicles (ROVs) used to cap the gulf oil leak also highlight the need for a better control strategy than simply using joysticks (Schneider, 2010). An additional consideration is that as the operator workload increases, the ability to control the robot slows down considerably, which may jeopardize mission performance. Current operator interfaces are simply not suitable for directing higher dimensional robots with human levels of capability. In order to reduce the operator workload and speed up robot performance, the level of interaction between operator and robot must be elevated from teleoperation to at least semi-autonomous control. At this level, the operator may direct the robot through gesturing or issuing voice commands. The cadre of advanced interfaces may also include non-invasive brain machine interfaces such as electroencephalography (EEG) that can decipher user intent based on"brain waves"(Bradberry et al, 2010). This level of command requires additional development of novel operator interfaces coupled with significantly enhanced autonomy embedded within the robot itself. In particular, an advanced semi-autonomous goal-directed task planning and execution system is needed for effective operation of high degree of freedom robots. While academic research on humanoid robots has produced motion planners capable of handling many degrees of freedom and complex situations, these planners require too much computation time, and are vulnerable to the disturbances that occur in unstructured environments. For example, task planners based on waypoints have been developed for unmanned aerial vehicles (UAVs), but these place significant limitations on maneuver detail even with relatively few degrees of freedom (Bowen et al., 2003). New approaches are needed that are capable of quickly generating, executing, and modifying plans for high degree-of-freedom robots in unstructured environments (Murphy, 2004). Users should be able to specify goals at a high level, such as reaching a goal state. For example, the operator should be able to simply point to the objects in their current location and tell the robot that they should be stacked in a new location, which is pointed to by the operator. Ideally, with this approach, no explicit OCU is required at all. The operator directs the robot through gestures and speech. This type of operator control interface represents a revolutionary advancement over the current situation, in which one or more operators must devote their full attention (and use both hands) to interact with a briefcase-sized OCU. Freeing operators from having to use such large and attention-intensive OCUs would make the robots more accessible to soldiers in the field, and to other personnel that are not trained to use OCUs. The autonomy system should automatically take advantage of spatial and temporal goal flexibility to enhance robustness and energy efficiency. The task execution system should incorporate necessary sensing and state estimation capabilities. This might include local terrain sensing vision or LIDAR systems to support locomotion, and stereo or time of flight vision and touch sensors to support manipulation. PHASE I: Conduct survey of robots with human-like mobility and dexterity being developed for medical applications. Develop operator interface design concepts that translate functional robot requirements into implementable task strategies. Develop an animated computer model of the robot and software emulation of operator interface(s) along with medically-relevant operational tasks. The prototype model should be capable of demonstrating a humanoid robot performing high level tasks using minimal user-operator intervention. Develop a complete plan for a Phase II proof of concept demonstration and model validation of the new operator interface and autonomous control. PHASE II: Build and demonstrate a working prototype Joint Architecture for Unmanned Systems (JAUS) compliant robot control unit that implements execution of high level tasks on two systems: (1) the CAD software model developed in Phase I, and (2) a humanoid robot hardware prototype of the proposer"s choice. JAUS standards and documentation can be found at References 11-13. The prototype control unit should be capable of demonstrating key elements of Army medical robotic tasks such casualty extraction, e.g., lifting a payload and placing it in a desired location using minimal user-operator invention. At least semi-autonomous operation must be demonstrated with the goal of maximum autonomy. PHASE III DUAL USE APPLICATIONS: Produce a ruggedized, deployable prototype control unit ready for demonstration and limited operational testing on a humanoid robot used in military and civilian emergency response scenarios, such as recovering injured personnel in mine, construction site and nuclear power plant accidents; chemical spills; fire fighting, terrorist, hostage situations; and, in police response to situations involving armed suspects. Commercialization of this technology could potentially save many lives among military and civilian emergency medical personnel, as well as among the targeted casualties and injured persons. REFERENCES: 1. Lane JC, Carignan C, Akin D: Advanced Operator Interface Design for Complex Space Telerobots, Autonomous Robots 11, Kluwer Academic Publishers, 49-58, 2001 2. Atwood T, Klein J: A life-size humanoid robot & #8232;that searches for & #8232;and rescues & #8232;people, Botmag, April 25, 2007. http://www.botmag.com/articles/04-25-07_vecna_bear.shtml 3. Yamauchi, Brian."PackBot: A Versatile Platform for Military Robotics,"In Proceedings of SPIE Vol. 5422: Unmanned Ground Vehicle Technology VI, Orlando, FL, April 2004, http://robotfrontier.com/papers/SPIEUGV.pdf 4. Ambrose R, Aldridge H, Askew RS, Burridge RR, Bluethmann W, Diftler M, Lovchik C, Magruder D, and Rehnmark F. Robonaut: NASA"s Space Humanoid. Humanoid Robotics, July/Aug. 2000, pp. 57-63. 5. Bradberry TJ, Gentili RJ, Contreras-Vidal JL. Decoding three-dimensional hand kinematics from electroencephalographic signals. Conf Proc IEEE Eng Med Biol Soc. 2009:5010-3. 6. Bowen, David G. and Scott C. MacKenzie, DEFENCE R & D CANADA,"Unmanned Vehicles: Technological Drivers and Constraints,"Sep 2003, http://pubs.drdc.gc.ca/PDFS/unc28/p519508.pdf 7. Murphy, Robin R."Human-Robot Interaction in Rescue Robotics,"Trans. Systems, Man, and Cybernetics, vol. 34, no. 2, 2004, 138153. http://www.cc.gatech.edu/~athomaz/papers/murphy04.pdf 8. USAMRMC TATRC Autonomous Combat Casualty Care Programs. http://www.tatrc.org/website_robotics/index.html 9. Department of the Army Pamphlet 525-7-15,"US Army Concept Capability Plan for Army Aviation Operations 2015-2024,"page 43, paragraph 2-11b(5)(e). http://www.tradoc.army.mil/tpubs/pams/p525-7-15.pdf 10. Schneider, David."The Gulf Spill"s Lessons for Robotics,"IEEE Spectrum, 47(8): pp9-12, August 2010. http://spectrum.ieee.org/robotics/industrial-robots/the-gulf-spills-lessons-for-robotics 11. Joint Architecture for Unmanned Systems (JAUS) Documentation: http://www.openjaus.com/support/jaus-documents 12. JAUS Transport Specfication: http://standards.sae.org/as5669a/ 13. Society of Automotive Engineers (SAE) Standard AS5669, JAUS/SDP Transport Specification: http://sae.nufu.eu/std/AS5669

OBJECTIVE: Develop autonomous terrain classification and driving control systems that enable medical robots and mobility assist devices to safely negotiate various types of terrain. Applications would include casualty assessment/extraction robots, chem/bio-hazard detection robots, and electric-powered wheelchairs. DESCRIPTION: The military is currently developing several robotic platforms for casualty triage/assessment, casualty extraction, medical resupply, and chemical/biological hazard detection that require navigation of hazardous terrain such as steep inclines, ice, mud, and loose gravel. These conditions can cause wheel/track slippage, sinkage, or in the worst case, overturn, resulting in end of mission. Hazardous terrain may also threaten electric-powered wheelchairs (EPW) and other mobility aids for wounded warriors and disabled veterans. Developing a driving control system that can reliably detect hazardous terrain and then implement safe driving control strategies would therefore be of great benefit to the military. To accomplish these objectives, two systems will need to be developed: (a) terrain sensing and classification system, and (b) terrain-dependent driving control system. The terrain classifier would identify the type of terrain (sand, grass, gravel, mud) based on visual and/or tactile sensory input. The robot control system would then make appropriate adjustments to driving parameters such as speed, acceleration, turning radius, and braking to avoid loss of control. Additional sensors may need to be retrofitted to the robot"s drive system to enable closed-loop control of the drive system. Terrain classification falls into two basic approaches: visual and tactile. Many autonomous ground vehicles developed for the military use vision-based approaches employing cameras and LIDAR [1]. While visual methods have been effectively showcased in events such as the DARPA Grand Challenge [2] and even on the surface of Mars [3], their performance can be greatly diminished under wet/snowy conditions, superficial ground coverings, and shadows. In addition, vision approaches may also have difficulty distinguishing between surfaces that look similar but have different texture, such as dirt versus mud. Alternatively, tactile approaches employ vibration sensors and measurements for slip estimation. Vibration methods are robust with respect to climatic conditions and ground coverings and are naturally able to sense the roughness in terrain that will directly affect driving control [4]. However, they cannot"look"ahead like cameras to anticipate dramatic changes in conditions such as an icy patch on the road. Slip estimation is often used to distinguish between wet and dry conditions, but implementation is challenging [5,6]. The most effective terrain classification system might therefore combine both visual and tactile approaches. Off-road driving experts have developed substantial lists of terrain-dependent driving rules in several sources to improve driving safety and efficiency on potentially hazardous surfaces such as snow, ice, mud, and loose gravel [7,8,9]. The main strategy behind these rules is to reduce wheel slip and thereby improve traction. The"Terrain Response"system used on the Land Rover LR3 and Freelander commercial vehicles [10] uses low-level, terrain-dependent feedback to prevent slipping via traction control and the anti-lock brake system (ABS). The operator selects from one of five modes (everyday, grass/gravel/snow, mud/ruts, sand, and rock crawl), which are then used to alter settings on the engine throttling, ABS, transmission, differentials, and traction/stability control systems. A substantial body of additional research has been conducted in the academic community on terrain-dependent traction control and ABS [11,12]. The Army has a demonstrated clear need for terrain-dependent driving control in medical robotics and assistive device applications. Such a system would significantly reduce risk and increase the probability of mission success. Recent advances in sensor technology, particularly in lasers/LIDAR and piezo-electric chips, have not only made deployment of terrain-dependent driving control feasible, but economically viable as well. This project is an initial step toward that goal. PHASE I: Determine the types of hazardous terrain that must be navigated by medical robots and mobility assist devices such as electric-powered wheelchairs. Identify terrain classification features that will allow safe passage across hazardous terrain. Design a preliminary terrain classification system and identify the sensors required. Conduct a literature survey of driving control rules for off-road vehicles and identify key driving control strategies that could be implemented in medical robotics applications. Develop a research plan for Phase II. PHASE II: Develop, integrate, and test terrain-dependent Joint Architecture for Unmanned Systems (JAUS) driving control on both a two-wheel drive mobility assist device (e.g., EPW) and a four-wheel drive medical robots. JAUS documentation and specification can be found at Referenced 13-15. Collect data to determine how these robots perform on different terrains and surfaces under different conditions including speed, turning radii, and acceleration. Use the collected data to determine driving rules for different terrains and integrate into the robot control system. Collect vibration and slip estimation data on a variety of terrains and surfaces at multiple speeds. Tune the terrain classifier for terrain-dependent control, and configure the terrain classifier for multiple speeds and loads. Develop a commercialization plan for Phase III. PHASE III DUAL USE APPLICATIONS: Assist the Army in transitioning and implementing the terrain classification and terrain-dependent driving control systems in two commercial applications: a four-wheel drive robot and electric-powered wheelchairs. Develop and market an inexpensive commercial version of the terrain classification and driving control systems for deployment on passive wheelchairs. REFERENCES: 1. A. Angelova, L. Matthies, D. Helmick, and P. Perona,"Fast terrain classification using variable-length representation for autonomous navigation,"Proceedings of the IEEE Computer Society Conference on Computer Vision and Pattern Recognition, pp. 18, June 2007. 2. J. Markoff:"Crashes and Traffic Jams in Military Test of Robotic Vehicles", New York Times, Nov. 5, 2007, http://www.nytimes.com/2007/11/05/technology/05robot.htm?_r=1 3. I. Halatci, C. A. Brooks, and K. Iagnemma,"Terrain classification and classifier fusion for planetary exploration rovers,"Proc. of the IEEE Aerospace Conference, pp. 111, March 2007. 4. K. Iagnemma, K. and S. Dubowsky,"Terrain estimation for high speed rough terrain autonomous vehicle navigation,"Proc. of the SPIE Conf. for Unmanned Ground Vehicle Technology IV, Orlando, Florida, 2002. 5. A. Angelova, L. Matthies, D. Helmick, and P. Perona,"Learning and Prediction of Slip from Visual Information,"Journal of Field Robotics, Vol. 24, No. 3, pp. 205-231, 2007. 6. D. Helmick, A. Angelova, and L. Matthies,"Terrain Adaptive Navigation for Planetary Rovers, Journal of Field Robotics, Vol. 26, No. 4, pp. 391-410, 2009. 7. B. Delong, 4-Wheel Freedom: The Art of Off-Road Driving, Paladin Press, Boulder, CO, 2000. 8. J. Allen, Four-Wheeler's Bible, MotorBooks, St Paul, MN, 2002. 9. C. Ordonez, and E. G. Collins, Jr.,"Rut Detection for Mobile Robots,"Proc. of the IEEE 40th Southeastern Symposium on System Theory, New Orleans, LA, pp. 334-337, March 16-18, 2008. 10. D. Vanderwerp,"What Does Terrain Response Do?", http://www.caranddriver.com/features/9026/ whatdoes-terrain-response-do.html 2005. 11. J. Van Der Burg and P. Blazevic,"Anti-lock braking and traction control concept for all-terrain robotic vehicles,"Proceedings of the IEEE International Conference on Robotics and Automation, Albuquerque, New Mexico, 1997. 12. P. Khatun, C. M. Bingham, N. Schofield, and P. H. Mellor,"Application of fuzzy control algorithms for electric vehicle antilock braking/traction control systems"IEEE Transactions on Vehicular Technology, Vol.52, No. 5, pp. 13561364, 2003. 13. Joint Architecture for Unmanned Systems (JAUS) Documentation: http://www.openjaus.com/support/jaus-documents 14. JAUS Transport Specfication: http://standards.sae.org/as5669a/ 15. Society of Automotive Engineers (SAE) Standard AS5669, JAUS/SDP Transport Specification: http://sae.nufu.eu/std/AS5669

OBJECTIVE: The objective of this topic is to develop an in vitro culture approach to generating the approximately 50 grams of brown adipose tissue or brown fat from autologous cells that could be used for re-implantation and prevention or treatment of obesity. Brown fat appears to arise from a progenitor cell that preferentially differentiates into white fat. Under certain conditions these progenitor (or pre-progenitor) cells can be induced to differentiate into brown fat. Factors that have been implicated in this pathway include cold exposure, cytokines, adrenergic modulation, enzymes, growth factors and specific phosphorylation pathways. DESCRIPTION: Obesity along with its metabolic concomitant condition, diabetes are becoming increasingly prevalent in the general population as well as the military. Increasingly personnel are being rejected for these factors or need to be deferred later because of acquired obesity during service. Brown fat is a primary site of energy expenditure through thermogenesis that is mediated by the uncoupling protein-1 located in mitochondria. Brown fat is present in mammals especially in babies and during hibernation. Human adults have also been shown to have brown fat (1,2). The present project seeks proposals that will use easily accessible cells from a given individual to generate brown fat for re-implantation in that same individual. The approach would help the overweight and obese by boosting energy metabolism and thus making weight loss and maintenance feasible. Increasing brown fat in rats in amounts comparable by weight to the 50 grams of brown adipose for humans noted above resulted in the body weights being 20% lower than that of normal animals. Even on a calorie-rich diet the animals did not put on weight. (3). A number of approaches have been utilized to study brown fat. PHASE I: Conduct a detailed design and feasibility study to define a prototype source and culture system for the generation of brown adipose tissue. The source of cells should be readily available, for example in a subcutaneous fat or muscle biopsy or circulating blood (3-6). Cell culture systems should be consistent with a smooth transfer to the clinic through ethical, legal, social, and regulatory constraints. No human or animal use studies should be conducted during this phase. PHASE II: Based on the detailed design of phase I, a prototype system shall be fabricated and demonstrated during Phase II. The performance of the prototype should be quantitatively tested and characterized. The evaluation data will be used to refine the initial prototype, improve its performance and validate improvement and potential performance using militarily relevant procedures. FDA will be approached to determine requirements for clearance should a given system prove efficacious in animal experiments. The product will be a patentable system to generate brown adipose tissue. PHASE III DUAL USE APPLICATIONS: Animal studies consistent with FDA input progressing to phase I/II human studies will be performed in this phase. It is expected that this work will set the stage for a pivotal trial of this approach to obesity/overweight. REFERENCES [1] Cypress A et al. NEJM 360:1509 [2] Higuchi T, Kinuya S, Taki J et al. Annals of Nuclear Medicine 18:547 (2004). [3] Veliopoulos A, Muller-Decker K, Strzoda D et al. Science 10:1126 (2010). [4] Kajimura S et al. Nature online 10:1038 (2010) [5] Petrovic N et al. JBC on line 285:7153 (2010) [6] Haas B et al. Sci. Signal. On line 210:1126 (2009). [7] Newson SA et al. J. Endo rinology on line preprint 5 July 2010. Also see: http://www.sciencenews.org/view/generic/id/45988/title/Creating_fat_that_burns_calories REFERENCES: