Thomas Murphy - US grants

Angiotensin II (angII) is the major effector molecule of the renin angiotensin system and a principal determinant of blood pressure and fluid volume. Progress towards an understanding of the molecular properties of receptors for angII (AT receptors) has lagged that achieved for other components of the renin-angiotensin system. Although evidence of AT receptor heterogeneity has accumulated over two decades, progress towards defining an AT receptor family has been hindered by a lack of information on receptor primary structure. On the basis of newly developed nonpeptidic ligands, the existence of two classes of AT receptors, termed AT1 and AT2, has been proposed. However, no known biological response has been associated with AT2 binding sites. Thus, its existence could not have been predicted by earlier studies. Therefore, diversity within the AT1 receptor class most likely accounts for early evidence of AT receptor heterogeneity. A cDNA encoding a rat vascular smooth muscle AT1 receptor has now been isolated. the amino acid sequence encoded by this clone shares seven hydrophobic, putative membrane spanning structures and conserved amino acid motifs with the rhodopsin-like superfamily of G-protein-coupled receptors. Genomic Southern analysis demonstrates several hybridizing bands to a cloned cDNA probe that suggests the possibility of molecular diversity in AT1 receptors. The objective of this proposal is to define rigorously the molecular basis for this diversity by isolating cDNAs and/or genes encoding additional AT1 receptor subtypes. Using a model system whereby each cloned receptor is uniquely transfected and expressed in a cell line, their pharmacological attributes and biochemical signalling mechanisms will be studied in the absence of AT receptor heterogeneity commonly found in other tissue models. Experiments are proposed to localize the tissue and cellular distribution of AT1 receptor subtypes using in situ hybridization and immuno-cytochemical approaches. These studies should improve knowledge of the pharmacology, function and distribution of AT receptors subtypes. They should improve the rational development of selective therapeutic agents for the treatment of cardiovascular disorders, and provide insights into potential pathophysiological roles of AT receptors.

DESCRIPTION: Angiotensin (AT) receptor antagonism shows promise as a strategy for therapeutic control of some forms of hypertension. Many of the effective, antihypertensive non-peptide AT1 receptor antagonists developed over the past several years have complex mechanisms of action. A need still exists to understand better the properties of these compounds as a need for more safe and selective drugs may arise in the future. One means of achieving this is to develop a model of AT1 receptor structure. Until unforeseen technological advances are made in purifying and crystallizing integral membrane receptor proteins, models of receptor structure can still be developed by combining site- directed mutagenesis with structure-activity-relationship (SAR) analysis. The fundamental goal of this research is to develop such a model by identifying molecular interactions of currently available AT peptides and non- peptide compounds with the AT receptors. The longer term benefit and ultimate test of this research would be the production of novel drug structures designed rationally from predictions of the spatial arrangement of AT receptor domains. The outcomes may be even more broadly generalized as a test for the utility of structural predictions for drug design and development for this broad class of proteins. Hypotheses are proposed to: 1) test the possibility that residues in extracellular domains of AT receptors are involved in AT peptide interactions, unlike for G-protein coupled receptors for biogenic amines; 2) to identify the receptor binding sites for the non-peptide phenylimidazole antagonist ligands and to understand the forces of interactions between the receptor and these compounds and 3) to determine if insurmountable antagonism of AT receptors by peptide and non-peptide antagonists results from a pharmacologic disequilibrium and not complex allostericism and to understand the structural and molecular basis for insurmountable antagonism. To begin to address these issues, the pharmacological, functional and molecular diversity of AT receptor species isoforms will be exploited to identify domains and specific amino acid residues in the receptors associated with their divergent phenotypes. Mutagenic strategies that include the exchange of divergent amino acid residues among differing AT receptor isoforms, are proposed as a first step in identifying these binding domains. Once sites of ligand contact have been established by this comparative approach, an empirical approach will be employed to refine the model, to reveal other residues that contact ligand which are common to all AT receptor isoforms, and to determine the specificity and forces dictating these receptor-ligand interactions. To achieve this, the effects of mutations at sites neighboring those identified by the comparative approach will be analyzed. The effects of a series of point mutations at any single of these sites will then be analyzed using radioligand binding and functional SAR studies, employing a diverse array of peptide and non- peptide ligand derivatives. Similar approaches will be employed to reveal the mechanisms of insurmountable antagonism of AT receptors, and to establish the molecular determinants that differentiate it from surmountable antagonism.

DESCRIPTION (provided by applicant): Vascular smooth muscle cells respond to a diverse array of extracellular ligands acting through cell surface receptors, many of which have been implicated as causative factors in vascular disease. Although these initiate complex streams of intracellular signaling information, little is known about how this complexity is integrated. Receptor signaling is well known to control transcriptionally acting processes, whereas little is known about control of processes that act at the post-transcriptional level. We propose to focus on mechanisms of the latter in the context of the problem of signaling integration. Our general hypothesis is that regulated post-transcriptional mechanisms in smooth muscle cells play as important a role in controlling immediate early gene expression as do regulated transcriptional mechanisms. We plan to develop three specific themes: i) To understand in one system whether multiple signaling pathways modulate functional post-transcriptional mechanisms. ii) To demonstrate that simultaneously triggered transcriptional and post-transcriptional mechanisms can cooperate synergistically in specifying immediate-early mRNA responses evoked by a stimulus. iii) To make progress in identifying molecular factors and/or molecular mechanisms that function as trans-acting agents mediating post-transcriptional responsiveness to receptor signaling. Our four specific aims are to: 1) To test the hypothesis that the 5' untranslated region of the vascular AT1 -R mRNA interacts with a complex of factors that include substrates of cAMP-dependent kinase signaling. 2) To test the hypothesis that mitogen-induced immediate-early COX 2 gene expression involves coordinate activation of factors that simultaneously function at transcriptional and post-transcriptional levels. 3) To test the hypothesis that signaling pathways and mechanisms involved in controlling immediate-early post-transcriptional modulation of IL-6 gene expression differ from those involved in COX 2 gene induction. 4) To test the hypothesis that changes in gene expression by activation of the 0 protein-coupled mating pheromone pathway in yeast can involve post-transcriptional mechanisms. This course of research will clarify both how the VSMC phenotype integrates signal transduction information and will continue solid progress in understanding the molecular and cellular basis of post-transcriptional regulation in gene expression.

As a group, the twelve investigators supervise vigorous research programs, share complementary research interests, and are amply supported by MH mechanisms. The design of this Molecular Imaging Unit is composed of three synergistic modules of equipment. The combination of these modules fully exploits the dramatic convergence of imaging technologies with the analytical methods used to study the regulation of cellular function and gene expression patterns. As the various world-wide Genome Initiatives are nearing fruition, we recognize unique opportunities to examine the significance of individual research problems on sub-genomic, and eventually genomic, scales. The Molecular Imaging Unit will both enhance our current research activities and facilitate our entry into this new and exciting direction of biomedical research. The first module is a Molecular Dynamics Storm 860 Phosphorimager/Fluorimager system, which will enhance data acquisition and quantitative analysis of experiments based upon protein and nucleic acid blots and gels. This module both fills a glaring gap in our present analytical capacity and will expand the utility of the additional modules in the Unit. The second module is a General Scanning Inc. ScanArray-5000 microarray slide reader, which will allow for comprehensive and quantitative analysis of gene expression patterns using gene microarray technology. The Storm 860 system will prove to be an, indispensable tool for full exploitation of the vast amount of information that will be collected by our investigators using microarray analysis. The third module is an Arcturus Laser Capture Microdissection PixCell II system. This device is used to extract individual cells or clusters of cells from complex tissues. Protein and nucleic acid content within these cells can then be subjected to further molecular analysis at either a sub- genome wide level, using microarray analysis, or to examine the modulation of specific molecules in the cells using the Storm 860 system.

DESCRIPTION (provided by the applicant): The immunosuppressants cyclosporin A (CsA) and FK506 cause a spectrum of serious side effects, including impaired cardiovascular function. This is not only a serious clinical problem, but also indicates that cellular processes affected by immunosuppressant are crucial for the maintenance of normal cardiovascular homeostasis. Through binding to either of two distinct cellular adapters, both drugs inhibit the phosphatase calcineurin. A family of transcription factors termed the nuclear factors of activated T-cells (NFAT) are well-known calcineurin substrates. Although initially considered T-cell restricted, studies indicate that NFAT isoforms are widely distributed in non-lymphoid tissues throughout the body. The applicant has published several studies supporting the general notion that NFAT can serve as a transcriptional effector for signaling evoked by various hormones, autacoids and growth factors within subsets of vascular smooth muscle and endothelial cells. We speculate that NFAT participates in the modulation of vascular gene expression programs elicited by such physiological agonists and that interference with NFAT mediated transcription may contribute to immunosuppressant drug toxicity. If so, on balance, NFAT likely serves as a key regulator of important homeostatic processes, and its targets would be of great interest to discover. General objectives of this project include deriving a better understanding of how NFAT mediated transcription operates in a vasculature smooth muscle cell context, and what genes it may be involved in regulating. To explore this, we will assess whether four distinct NFAT isoforms are differentially regulated and drive unique patterns of vascular gene expression. Since no NFAT gene targets in smooth muscle cells have been definitively described, we will carry forward studies that strongly support the hypothesis that NFATs trans-activate the COX-2 and IL-6 genes within VSMC. We will also study how co-activation of cAMP-dependent kinase pathways modulate NFAT transcription. Lastly, we will examine the physiologic consequences of disrupted NFAT function by studying how CsA treatment and NFAT gene ablation influence vascular function using murine models. The project will exploit innovative and powerful recombinant gene expression techniques in cultured cell models, coupled with state-of-the-art physiological assessments. Our expected findings are likely to provide important new insights into the role of NFAT in vascular smooth muscle and its relationship to immunosuppressant-induced vascular dysfunction.

A consortium of four community colleges, each serving a geographically defined region, together with seven affiliate supercomputer sites and business partners, constitute a National Science Foundation Advanced Technology Education Center of Excellence for High Performance Computing (HPC) technology. High Performance Computing refers to multi-processor computers performing complex computational operations with a particular focus on clusters. Each college in the consortium has at least one partner High Performance Computing facility, referred to as an HPC site. The National Center is partnering with business and industry to develop skill set standards and competencies needed for certifying HPC technicians and for developing an articulated Associate Degree program in HPC technology. The Regional Education and Training Centers (RETCs), established at each community college, are developing curricula in HPC Technology that articulate with four- year college information science, computer science, and high performance computing technology programs and that include the establishment of 2 + 2 agreements with regional high school Tech Prep Programs.

Maui Community College is the lead institution in a consortium with Wake Technical Community College, Pellissippi State Technical Community College, and Contra Costa College, each chosen because of the diversity of student populations, partnerships with HPC sites and regional business and industry, and potential four-year college affiliations. An NSF planning grant (award 0101643) supported a nation-wide survey that revealed that within the next 2 to 5 years, a) 71% of surveyed business and industry will utilize high performance computing, (2) PC-cluster use will grow by 9% and there will be a distinct shift offsetting the balance between PC-cluster and supercomputer use in favor of PC-clusters and c) industry will continue to struggle to recruit, train and/or retain HPC employees.

The National Center administrator is responsible for (a) creating and administering a web-based certification examination for technical personnel, (b) overseeing curriculum development and teaching methodologies, (c) developing strategies for recruitment, retention and placement; (d) creating a national repository of PC-cluster software, curricula and training materials for HPC technician educational programs; (e) providing professional development activities for college faculty, secondary teachers and business professionals; (f) developing and providing a consortium communications infrastructure; and (g) supervising dissemination, evaluation and reporting activities.

RETC directors are responsible for (a) developing curriculum and learner centered teaching methodologies, (b) educating faculty, people from business and industry, and secondary teachers in PC-cluster construction, management and use; (c) providing professional development activities; (d) developing and coordinating professional internship programs at HPC sites and business for college faculty and secondary teachers; (e) coordinating student internship programs; (f) assisting with program graduate placement and (g) developing four-year college articulation agreements and local high school 2 + 2 agreements.

APOLLO (Apache Point Observatory Lunar Laser-ranging Operation) is a next-generation laser-ranging apparatus capable of obtaining lunar ranges with millimeter accuracy. Relying on the still-operational retroreflector arrays placed on the lunar surface by Apollo astronauts, APOLLO
constitutes the ground-link of a dynamically clean orbital laboratory. APOLLO will bring new life to lunar ranging by applying advanced laser and detector technology on a large telescope, by incorporating precision gravimetry, millimeter-accuracy GPS positioning, and a meteorological
array on the site, and by forming a tight interface between the observation and data analysis efforts.

The order-of-magnitude improvement in range precision expected from APOLLO will advance by a similar factor the scientific power of lunar ranging to determine a number of qualitative aspects of the fundamental properties of gravity. Among the tests that lunar ranging currently leads are tests of the equivalence principle, time variation of the gravitational constant, geodetic precession, gravitomagnetic effects, and the possible presence of long-range forces. Through its comprehensive investigation of the nature of gravity, lunar ranging addresses the question: is general relativity correct? The technique, ambitious goals, and connection to our remarkable history of space exploration make APOLLO especially appealing to the public, presenting excellent outreach potential. The APOLLO team is committed to sharing the excitement of this project with its immediate community and beyond.

Murphy
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Nonlinear optical devices are expected to play a growing role in optical networks by replacing costly electronic components with fast optical processes. One critical challenge faced by nonlinear devices is that they can require impractically high power or long lengths to achieve a sufficient interaction. A new type of nonlinear optical detector is proposed that uses low-loss integrated waveguides and nanofabricated Bragg resonators to amplify the nonlinear interaction. The underlying nonlinear mechanism to be exploited is two-photon absorption in semiconductors: a process that has applications including optical autocorrelation, temporal demultiplexing, optical sampling, optical memory, and clock recovery. This research could lead to a new generation of ultrafast nonlinear components that operate at hundreds of Gb/s, occupy very little space on a chip, and require less than 100 microWatts of optical input power.

The educational objective of this CAREER award is to imbue students with excitement for science in the classroom and the laboratory. For K-12 students, a series of inquiry-based hands-on experiments will be produced that reveal how optics and optoelectronic devices are used in everyday life. For undergraduate students, involvement in research will be promoted through well-defined short-term summer and semester research projects that are specifically suited for undergraduate students. At the graduate level, the PI will continue to develop and update a unique course in optical communications which combines a rigorous treatment of the physics of fiber and integrated optics with research projects and numerical simulation.

APOLLO (the Apache Point Observatory Lunar Laser-ranging Operation) aims to test the foundations of our current theory of gravity--Einstein's General Relativity--by measuring the shape of the lunar orbit to one-millimeter precision. The technique involves bouncing laser pulses off reflectors placed on the moon by the Apollo astronauts. Measuring the round-trip time-of-flight of the laser pulses determines the distance to the moon, thus allowing the shape of the lunar orbit to be traced.
Prior to APOLLO, this technique determined the lunar orbit shape to 2-3 cm precision, and verified the correctness of General Relativity to about the 0.1% level of precision. By using a 3.5 meter telescope and modern instrumentation, APOLLO is capable of one-millimeter range precision, and will thus allow 0.01% precision tests of General Relativity. APOLLO is now in routine operation collecting its first data. Under this award, APOLLO will refine its technique and produce its first scientific results. The simple elegance of the lunar ranging technique, coupled with its connection to our historically inspiring Apollo lunar program, make APOLLO an apt vehicle for communicating the excitement of science to the public. This award is co-funded by the Physics Division and by the Office of Multidisciplinary Activities in the Mathematical and Physical Sciences Directorate.

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).

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Murphy


This NSF award by the Biosensing /CBET program supports work by Professor Murphy at University of Maryland College Park to develop a label-free biosensor that uses optical waveguides and resonant cavities comprised of nanoporous silicon. Nanoporous silicon is a unique material with several features that make it attractive for biological sensors, including a very high surface area to volume ratio, simple and inexpensive fabrication techniques, and suitability for integration with silicon electronics. The proposed sensor is designed to measure small changes in the refractive index of porous silicon waveguides that occur when biological molecules attach to the internal surfaces. In addition to the promise of improved sensitivity, this approach could be faster and less expensive than conventional techniques that require fluorescent labels. As a target application, they will explore the possibility of detecting prions, the protein molecules responsible for transmissible spongiform encephalopathies.
Beyond these intellectual goals, the project will also provide summer research opportunities for undergraduate students, mentoring for high-school students, and will promote multidisciplinary collaboration between chemists, biologists and optical engineers.

The recently built Apache Point Observatory Lunar Laser-ranging Operation (APOLLO) has become the premier lunar laser ranging (LLR) facility in the world, delivering one-millimeter range precision between Earth and Moon as a way to test General Relativity. General Relativity makes specific predictions about the shape of the lunar orbit, so that we may use the Moon as a laboratory, made possible by the reflectors left on the Moon by the Apollo astronauts and unmanned Soviet rovers. The goal of this work is to extend high-quality LLR observations over an additional three-year period, simultaneously collecting calibrated measurements of local gravity well enough to determine site displacements at the millimeter level. In tandem, an intensive effort will be initiated to advance the solar system model to a state that can take advantage of millimeter-quality data. It is by comparison to a complete and sophisticated model that questions relating to gravity, geophysics, and lunar physics can be explored. Though not the main focus, knowledge of the lunar interior stands to gain the most from APOLLO, as the experiment routinely acquires 4 to 5 reflectors in one session, providing exquisite measurements of the lunar orientation and distortion. But this refined knowledge of the moon will also facilitate understanding of how the moon moves in its orbit, as such information is crucial to determining the path of the Moon's center of mass through space.

LLR tests many fundamental aspects of gravity, like the equivalence principle, the constancy of gravity, gravitomagnetism, and the inverse-square law. Improving our knowledge of gravity therefore informs a diverse range of cosmologists, astrophysicists, particle physicists, and string theorists. This effort will also contribute to Earth and planetary science, especially via the inclusion of the superconducting gravimeter data. The open-source solar-system analysis code emerging from the project will provide an interesting platform for analyzing a wide range of data sets, including radar ranging in the solar system, Doppler radar to spacecraft around the solar system, pulsar timing experiments, etc. The same platform can form the basis of covariant studies for future proposed space missions that aim to test fundamental physics. Additionally, graduate student and postdoctoral training is a valuable component of the total effort. Finally, APOLLO will continue its strong tradition of public outreach, including featured appearances on popular television shows.

This award is to support hosting LittleFe buildouts as part of the HPC Educators Program at the Supercomputing 12 and Supercomputing 13 Conferences, and for the first external evaluation of the LittleFe project. LittleFe is a complete 6 node Beowulf style portable computational cluster which supports shared memory parallelism (OpenMP), distributed memory parallelism (MPI), and GPGPU parallelism (CUDA). These low-cost light-weight units are well-suited for institutions and teaching environments that do not have access to parallel platforms for parallel and distributed computing education. Teaching key concepts such as speedup, efficiency, and load balancing are much more effectively done on a parallel platform. These units will also support parallel programming and distributed computing in the undergraduate CS curriculum at colleges and universities. They will also support student programming contests which will be hosted at e.g. the XSEDE12 and XSEDE13 conferences, and outreach events at junior and senior high schools across the United States.

This award supports the continuation of the Research Experiences for Undergraduates (REU) program at the University of Maryland College Park. The main goal of the program will be to introduce undergraduate students to the university research environment through participation in frontier research. Participating undergraduates become members of research groups and are mentored by faculty members, post-docs and graduate students. Students see first-hand and participate directly in the research process. Past research topics have included: nano-photonic devices, spatio-temporal chaos and synchronism of chaotic systems, chaotic microwave circuits, dynamics of granular media, development of singularities in fluids and solids, nonlinear dynamics in optical systems and charged particle beams, magnetic reconnection, and turbulence and nonlinear phenomena in plasmas. Seminar series will complement and reinforce the learning experience. Student projects and presentations will be judged on the final day of the program, and winners will be funded to present their work at a relevant national conference. In addition, the summer program offers seminars and trips that expose students to a wide variety of subjects and opportunities. This will likely include trips to nearby government research laboratories, and lectures on topics such as applying to graduate school.

Objective: The proposed research seeks to develop a new type of graphene photodetector that operates at room temperature and exploits plasmonic resonances to achieve tunable spectral sensitivity throughout the terahertz spectral regime.

Intellectual Merit: Graphene is a unique two-dimensional material that has the potential to transform the field of terahertz and infrared photonics. Favorable thermoelectric transport properties, including low specific heat and weak electron-phonon interaction allow for sensitive detection and ultrafast response time in graphene devices. While a single layer of graphene can yield a small, but measurable photoabsorption, structured graphene films can support collective plasmonic excitations that show a far greater photoabsorption, at a resonance frequency that can be electrically tuned through the application of a gate voltage. The device concept proposed here could lead to a transformative advances in terahertz photonics, by enabling tunable room-temperature sensitivity and noise performance that is orders of magnitude superior to existing detector technologies.

Broader Impact: Practical room temperature terahertz photodetection could have far reaching impact in a number of key sectors ranging from pharmaceutical development to homeland security and medical imaging, and could spur the development of a robust terahertz technology. Furthermore, we propose a new outreach activity that would introduce young scientists from developing countries to new economical techniques for advanced signal recovery.

The University of Pennsylvania's central computing organization is partnering with leading campus researchers in engineering, physics, biology, pathology, genomics, bioinformatics, and computer science to optimize the campus network in support of big data research and high-performance computing. This project establishes a 100 Gbps-capable Science DMZ that is distinct from the general purpose campus network and is engineered for research applications. Additionally, it extends 10 Gbps connectivity to select research projects and increases Penn's connection to Internet2 from 1 Gbps to 100 Gbps, while also extending that connection to the Science DMZ. The project also lays the foundation for further enhancements to research networking infrastructure by extending IPv6 capabilities; upgrading network monitoring tools such as perfSONAR; and enhancing Penn's ability to support experimental networks and network architectures, including OpenFlow and Software Defined Networking.

The project will benefit a range of scientifically meritorious research. It will provide support for the large-scale data transfer, processing, and storage needs of researchers across Penn, while supporting intra- and inter-institutional collaborations and the broad dissemination of research results. Rather than focusing on the logistics of data storage and transfer, researchers will be able to concentrate on the transformation of these data into the information that will drive new discoveries and the creation of new technologies, drugs, therapies, and cures. Network enhancements will also support Penn's commitment to integrating research and education by supporting the network needs of the cross-disciplinary Penn Institute for Computation Science that where faculty actively integrate computation-based research with the training of future generations of STEM researchers.

Gravity, the most evident force of nature, is in fact the weakest of the fundamental forces, and consequently the most poorly tested. Einstein's general relativity, which is currently our best description of gravity, is fundamentally incompatible with quantum mechanics and is likely to be replaced by a more complete theory in the future. A modified theory would predict small deviations in the solar system that could have profound consequences for our understanding of the Universe as a whole. Lunar laser ranging (LLR), in which short laser pulses launched from a telescope are bounced off of reflectors placed on the moon by U.S. astronauts and Soviet landers, has for decades produced various leading tests of gravity by mapping the shape of the lunar orbit to high precision. The group proposes to continue conducting leading-edge observations with the Apache Point Observatory Lunar Laser-ranging Operation (APOLLO), in an effort to subject gravity to the most stringent tests yet. APOLLO, situated atop a 9,200 ft summit in Southern New Mexico, introduces a new regime of millimeter-precision in measuring the lunar orbit. However, incomplete models are thus far unable to confirm the accuracy. The group will therefore seek to build a calibration system to ensure that APOLLO meets its millimeter measurement goal, in addition to continuing the observation campaign. The proposed work will benefit the broader community in a number of ways. On the intellectual front, improving our knowledge of gravity informs a diverse range of cosmologists, astrophysicists, particle physicists, and string theorists. The effort would also contribute to Earth and planetary science, especially via measurements produced by the superconducting gravimeter. The APOLLO team will continue a track record of engagement in education and outreach activities, and will no doubt continue to attract public interest through print, web, radio, and television media.

Among other attributes that contribute to APOLLO's superior observations, routine ranging to all five lunar reflectors on timescales of minutes dramatically improves our ability to gauge lunar orientation and body distortion. This information allows a more precise determination of the path for the Moon's center of mass, thereby facilitating tests of fundamental gravity. Simultaneously, higher precision range measurements, together with data from a superconducting gravimeter at the Apache Point Observatory and from a high-quality Global Positioning System (GPS) station 2.5 km away, will greatly improve our understanding of the instantaneous location of the Observatory with respect to the Earth's center of mass (needed for the gravitational tests) by exposing subtle Earth dynamics that must be incorporated into the model. LLR measurements provide the best available tests of the strong equivalence principle, the time-rate-of-change of Newton's gravitational constant, gravitomagnetism, the inverse-square law, and preferred frame effects. In addition to these classical gravitational tests, APOLLO will permit testing of new ideas in physics relating to dark energy, extra dimensions, and violations of Lorentz Invariance. A large part of the effort proposed here is the construction of an absolute calibration system based on a cesium clock standard, a low-jitter short-pulse laser, and a precision interval counter. This system will provide an independent check of APOLLO's fundamental measurement, potentially identifying faults and confirming their pursuant remediation.

This award supports the renewal of the Research Experience for Undergraduates (REU) site in non-linear dynamics at the University of Maryland. The main goal of the program is to engage undergraduate students in cutting-edge research in the area of nonlinear dynamics. Through guided mentorship by faculty members and interactions with post-docs and graduate students, undergraduates will gain hands-on experience by participating directly in the research process. One major impact of the program of the program will be in the education of the next generation of scientists and engineers. Further, the program offers seminars and trips that expose students to a wide variety of subjects and opportunities while building a sense of community. Another impact of the program takes the form of the refereed publications generated by the research efforts of the TREND students and other program participants, in addition to the conference presentations that arise from the program.

The site will support ten undergraduates per summer in ten weeks of research. Potential research topics include: magnetic reconnection, turbulence, and nonlinear phenomena in plasmas; chaos and synchronism in large systems of network-coupled components; dynamics of granular and soft-matter flow; development of singularities in fluids and solids; nonlinear dynamics in optical systems and charged particle beams; autonomous control of vehicles with forecast uncertainty; and nonlinear physics of living systems. Two weekly seminar series will complement and reinforce the learning experience. The first seminar series will expose students to state-of-the-art research in nonlinear science at a level appropriate for undergraduates. The second seminar series will focus on research skills development, including critical reading of research papers, oral and written communication, and preparation for graduate school. Students will give oral presentations and participate in a poster session on the final day of the program, and funding will be provided to all students to subsequently present their work at a relevant national or regional conference.

Many phenomena in natural and engineered systems are both spatial and temporal, meaning that they involve dynamical changes and movements of nonuniform patterns. Examples include wave propagation, heating and cooling, chemical reactions, and diffusion. The ability to visualize these phenomena is fundamentally limited both by how fast they are and how small they are. Science has made remarkable improvements in the spatial resolution of microscopes, which has enabled the now-mature field of nanotechnology. At the same time, pulsed laser systems can resolve dynamical processes with femtosecond resolution -- far faster than even the best electrical detectors or cameras. This project aims to develop a novel instrument that will combine the spatial capabilities of a near-field microscope with the temporal resolution of a femtosecond laser, which is currently not available in commercial instruments. This tool will be capable of resolving nanoscale spatial structure, while simultaneously measuring ultrafast effects with femtosecond resolution in systems ranging from nanoelectronic devices to metallic nanostructures and solar cells. The unique instrument will provide valuable training for scientists and students at all levels, who will both develop and utilize it.

The combination of two different technologies, the femtosecond laser and the near-field microscope, will require significant engineering research, iteration, optimization, and system integration over the three-year period of this project. The proposed instrument will replace the continuous-wave laser typically used in a near-field scanning optical microscope with an ultrafast tunable pulsed laser, in order to produce an intense spatially and temporally localized optical stimulus that can excite nonlinear effects in the material or device at the nanoscale. A second, weaker temporally-delayed optical pulse will then be used to probe the properties and dynamics with femtosecond resolution. The proposed system will allow for time-resolved and spatially-resolved measurements at wavelengths ranging from 340 nm to 12,000 nm. The new instrument will enable the study of hot-carrier dynamics in metals and two-dimensional (2D) materials, investigation of the dynamic electrical response of perovskite materials for advanced optoelectronics, direct imaging of nanophotonic devices and resonant structures, and observation of heterogeneous surface chemistry and grain boundaries in transition-metal oxides.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.