Research - Science & Engineering Recipient   California Institute of Technology City   Pasadena, CA Description   Based largely on recent observations of the Cosmic Microwave Background (CMB), cosmologists believe that the entire observable Universe was spawned in a fraction of a second by the superluminal “inflation” of a sub-atomic volume. This paradigm presents a remarkable opportunity. Inflation produced a Cosmic Gravitational-wave Background (CGB) that may be detectable now via a faint signature imprinted in the polarization of the CMB. To do so could probe the very moment at which the Universe sprang into existence and explore energies far higher than will ever be achieved in terrestrial accelerators. This project will search for the signature of the CGB due to inflation using a set of novel, microwave polarimeters sited at the South Pole. A prototype experiment now in its third year of operation at the South Pole has proven the methodology. A full set of more capable polarimeters is proposed to be built. This technique will allow a search for the CGB with sensitivity exceeding that targeted by the Task Force on CMB Research for a future orbital mission, at least a decade earlier and at ~ 1% of the cost of an orbital mission. A detection of the signature of the CGB would be an historic achievement for both cosmology and high-energy physics. (Amount Awarded:$2,300,000) Recipient   Princeton University City   Princeton, NJ Description   This grant proposes to develop a novel microscope to probe and manipulate quantum dynamics in real time on the nanometer scale and use it to identify the physical processes that limit the implementation of materials in quantum computing applications. Scanning tunneling microscopes (STMs) have evolved into powerful tools that can image and manipulate single atoms and are now routinely used to unveil phenomena at the nanoscale. These instruments operate by mapping on the microscopic scale interaction between a sharp probe and the sample. However, the most advanced nanoscale microscopes developed to date cannot probe quantum dynamics in real time, as they operate at low frequencies and are insensitive to phenomena that occur on faster timescales. Development of a high-frequency STM will enable a new generation of experimentation in which quantum dynamics can be measured and manipulated on an unprecedented scale. This instrument will allow researchers to characterize directly processes that limit the use of materials for quantum computing applications and to correlate these limitations with the nanoscale properties of the materials. Beyond quantum computing, the proposed microscope breaks new ground in the measurement of properties of matter and should create opportunities for discovery across a wide range of areas. (Amount Awarded:$1,300,000) Recipient   University of California, Davis City   Davis, CA Description   The routine observation of high-resolution atomic scale information of biological specimens has been a long-term goal for microscopy. Recent advances in microscopy for materials science, such as the high-resolution scanning transmission electron microscopy (STEM) and spherical aberration correction, have finally put the goal within grasp. Combining the knowledge of materials science and biology, the research group will develop a new electron detector tailored to maximize the efficiency of this new technology for determining atomic scale structural information of membrane proteins -an important class of proteins, which are the target of most pharmaceutical agents. The detector design will produce a number of signals, which will be analyzed and processed with custom written computer codes. The development of this detector along with the protocols for implementation may have the potential to revolutionize the way structural biology acquires its most fundamental data. (Amount Awarded: $1,200,000) Recipient   University of California, Santa Cruz City   Santa Cruz, CA Description   What if costly, high-end microscopes could be replaced with tiny chips that detect, analyze, and manipulate single biomolecules, in a spirit similar to the replacement of bulky vacuum tubes with planar transistors that created the integrated circuit? Single biomolecules and macromolecular complexes are nanoscale objects, and to build, manipulate and observe objects of this size requires specialized tools. A team at the University of California, Santa Cruz will obtain cutting-edge, versatile nanofabrication equipment and bring together an interdisciplinary group of leading experts and their students spanning the range from device engineering to molecular biology. They will define nanoscale features on integrated optofluidic chips in order to optimize them for single particle studies. These chips will then be the basis for comprehensive studies of properties and functions of some of the basic building blocks of life: ribonucleic acids (RNA) and their macromolecular complexes. (Amount Awarded: $1,500,000) Recipient   University of Hawaii at Manoa City   Honolulu, HI Description   The overall goal of this project is to comprehend the chemical evolution of the Solar System. This will be achieved through an understanding of the formation of carbon-, hydrogen-, oxygen-, and nitrogen-bearing (CHON) molecules in ices of Kuiper Belt Objects (KBOs) by reproducing the space environment in a specially designed experimental setup. KBOs are small planetary bodies orbiting the sun beyond the planet Neptune, and are considered as the most primitive objects in the Solar System. A study of KBOs is important because they resemble natural “time capsules” at a frozen stage before life developed on Earth. The methodology is based on a comparison of the molecules formed in the experiments with the current composition of KBOs; such an approach provides the potential to reconstruct the composition of icy Solar System bodies at the time of their formation billions of years ago. The significance of this project is that it will elucidate the origin of biologically relevant molecules and help unravel the chemical evolution of the Solar System. Since KBOs are believed to be the main reservoir of short-period comets, which are considered as “delivery systems” of biologically important molecules to the early Earth, the project will also bring a better understanding of how life might have emerged on Earth. (Amount Awarded:$1,200,000) Recipient   University of Maine City   Orono, ME Description   Ice cores provide highly robust, sub-annually resolved, multi-millennial reconstructions of past chemical and physical climate essential to understanding climate change because instrumented climate records barely cover the last 100 years and significantly longer perspective is required to assess current and predict future climate. Researchers at the University of Maine Climate Change Institute have longstanding experience in ice core research and have contributed to major climate science realizations. The team has a vision for the future of climate research that includes: completion of a global array of ice cores before many of these records are destroyed by warming; development of interactive climate data search engines utilizing ice core records as a framework; and, through the proposed work, cutting edge innovations. These innovations require purchase of a laser ablation inductively coupled plasma spectrometer and associated development of an innovative cold stage sampling system to allow unprecedented increase in sample resolution, efficiency, and through flow for over 40 elements. Support is also sought to develop radically new, in situ ice core measuring capability utilizing novel thin film chemical sensors embedded in an ice core drill, and a "disposable" GPS system for remote sampling in extremely hazardous environments needed for ice core site reconnaissance and interpretation. University of New Mexico, Albuquerque Jean-Claude Diels, PhD $1,100,000 The quest to visualize ever smaller structures has driven scientific progress. Spatial resolution and contrast, essential factors in imaging, are limited by the wavelength and the intensity noise, respectively. While shorter wavelengths (X-rays, electron beams) can improve resolution and fluorescent labeling can increase contrast, these benefits come at the expense of harmful radiation and invasive sample preparation. The project team proposes an optical instrument based on making differential measurements on the phase of two circulating ultrashort laser pulses in order to achieve unprecedented spatial resolution and sensitivity. The underlying physical principles, established in prior research programs at UNM, are the conversion of phase (or distance) as small as a billionth (10-9) of a wavelength inside a laser to a measurable frequency and the discovery that the injection of even one trillionth (10-12) of one pulse into the other is sufficient to change measurably the frequency of the latter. Equipped with mechanical nano-positioners, the complete instrument, which will be called the Scanning Phase Intracavity Nanoscope (SPIN), will provide three-dimensional images of biological objects with a spatial resolution of 1nm. To be housed in the Cancer Research and Treatment Center Microscopy Facility, SPIN has the potential to serve the biomedical community by opening a new window to the intra-cellular nanoworld. (Amount Awarded:$1,600,000) Recipient   University of New Mexico City   Albuquerque, NM Description   The quest to visualize ever smaller structures has driven scientific progress. Spatial resolution and contrast, essential factors in imaging, are limited by the wavelength and the intensity noise, respectively. While shorter wavelengths (X-rays, electron beams) can improve resolution and fluorescent labeling can increase contrast, these benefits come at the expense of harmful radiation and invasive sample preparation. The project team proposes an optical instrument based on making differential measurements on the phase of two circulating ultrashort laser pulses in order to achieve unprecedented spatial resolution and sensitivity. The underlying physical principles, established in prior research programs at UNM, are the conversion of phase (or distance) as small as a billionth (10-9) of a wavelength inside a laser to a measurable frequency and the discovery that the injection of even one trillionth (10-12) of one pulse into the other is sufficient to change measurably the frequency of the latter. Equipped with mechanical nano-positioners, the complete instrument, which will be called the Scanning Phase Intracavity Nanoscope (SPIN), will provide three-dimensional images of biological objects with a spatial resolution of 1nm. To be housed in the Cancer Research and Treatment Center Microscopy Facility, SPIN has the potential to serve the biomedical community by opening a new window to the intra-cellular nanoworld. (Amount Awarded:$1,100,000) Recipient   Buck Institute City   Novato, CA Description   Scientists at the Buck Institute share a common goal: to understand aging. We have recently made key discoveries that point to a deep mechanistic relationship between disease and aging across diverse species and various age-related diseases. Our collective data suggest that, rather than viewing aging as a risk factor, it may be more accurately viewed as a principal causal factor of these disorders. We propose to test the hypothesis that age-related human disease is the result of segmentally-accelerated aging--in other words, that diseases of aging such as Alzheimer's disease, prostate cancer, and osteoporosis are part and parcel of the fundamental aging process itself, simply enhanced in the affected tissues. This is based in part on our recent discovery of an acceleration of the aging process in terms of oxidative modification to mitochondrial complex I (CI) in affected regions of the Parkinsonian versus the normal aging brain; selective inhibition of this enzyme complex has been long associated with Parkinson’s disease (PD). To test our hypothesis, we propose two experimental programs: (1) to undertake a functional analysis of mitochondrial post-translational modifications (PTMs) particularly in CI to determine which are critical for neuronal cell dysfunction, death and progression of PD; and (2) to test the generality of this mechanism by surveying Alzheimer's disease models and post-mortem patient brain tissues for mitochondrial PTMs and their functional correlates particularly but not limited to mitochondrial complex IV whose inhibition has been suggested to be preferentially involved in this age-related disorder versus changes associated with normal aging. (Amount Awarded:$1,500,000) Recipient   J. David Gladstone Institutes City   San Francisco, CA Description   The ability to control one’s movements is essential to life. Neural circuits involving the basal ganglia are critical for proper motor control, and disruption of these circuits leads to movement disorders such as Parkinson’s disease and Huntington’s disease. The striatum, which is the input nucleus of the basal ganglia, is a major site of activity-dependent plasticity in both health and disease. Because the striatum lies upstream of other basal ganglia nuclei, cellular and synaptic plasticity within this region alters the transfer of information throughout basal ganglia circuits. However, studies of the striatum have been hampered by difficulties identifying different types of cells during both in vitro and in vivo experiments. Here, we propose to utilize recently developed optical and genetic technologies to characterize the properties of striatal neurons and the neural circuits in which they are embedded. In vivo fiber optic technology will be used in conjunction with expression of channelrhodopsin and halorhodopsin to identify and directly drive neural activity in striatal neurons of awake behaving mice. These experiments will allow us to address how the rate and timing of activity in basal ganglia circuits are causally related to motor behavior. The ultimate goal is to develop a framework that will enable the rational design of novel therapies for devastating disorders affecting the striatum. (Amount Awarded: $1,500,000) Recipient   Northwestern University City   Evanston, IL Description   Little is known about the signaling networks that support the integration of the male and female germ cells into a new totipotent cell, the one-cell embryo. We propose that heretofore poorly understood inorganic signaling molecules initiate the massive changes in the physiology of a fertilized egg. Based on preliminary studies, the team hypothesizes that fluxes in zinc ions mediate the first definitive signal in embryonic development. This hypothesis will be tested by two approaches: one targets real time changes in the subcellular concentrations of free zinc and calcium in live cells and the other rigorously maps specific changes in the total zinc pools at the nanometer level. The mouse oocyte is an ideal model system to study this novel inorganic signaling pathway. It undergoes a clear developmental pattern of receptor-mediated events as it transitions from a dormant stage to a fully active state upon fertilization. Also, its large size facilitates spatial localization of key molecular players. New analytical tools will be developed to map the abundance of specific inorganic molecules and biological receptors. (Amount Awarded:$1,600,000) Recipient   Stanford University City   Stanford, CA Description   Excitable cells are the biological building blocks of brain, heart, and muscle, and communicate and compute using tiny, transient electrical currents. Widespread throughout the body, these cells underlie remarkable behaviors, from orchestration of movement to high-level cognition. When they malfunction, these cells give rise to devastating diseases, ranging from heart failure to Parkinson's disease to depression; however, the interventional tools currently available to deal with these conditions are exceedingly primitive, have severe side effects, and yield little or no understanding of healthy cells or of disease processes. New technology is required, powerful enough to address the high speed and structural complexity of these electrical tissues. This grant is for a four-year project to address this fundamental obstacle by developing and applying emerging optical technologies first developed at Stanford. This light-based bioengineering approach has the power to control cellular functioning in vivo with millisecond precision, and to control intracellular messengers in specific cell types, thereby opening new vistas of both investigation and healing. The project personnel will develop the science and technology of this approach and apply these tools for the first time to mammalian models of neurological, neuropsychiatric and cardiac disease, spanning the central, peripheral, and autonomic nervous systems. (Amount Awarded:$1,500,000) Recipient   University of Colorado at Boulder City   Boulder, CO Description   This proposal requests support to develop innovative research strategies in mass spectrometry in order to detect and characterize all proteins in a cellular "proteome" (i.e. all proteins present in a single cell type). Mass spectrometry is the most powerful tool for addressing this problem and worldwide efforts are underway to define the proteomes of organisms, tissues and fluids. However, such efforts are stymied by the inability to comprehensively observe all proteins in highly complex biological samples. The goal is to create innovative experimental and computational technologies that will enhance the accuracy and sensitivity of protein detection by mass spectrometry, and enable comprehensive protein identification. In order to expand the depth to which the proteome can be observed, funds will be used to purchase a high resolution mass spectrometry system with capabilities for electron transfer dissociation. With this instrument, new methods will be developed to overcome limitations in data collection and solve major hurdles in recovering information from large scale datasets. These will be applied to collaborative research efforts between eight laboratories, providing the possibility for unprecedented capabilities to answer questions that were previously impossible to address. (Amount Awarded: $1,200,000) Grants awarded prior to new criteria and geographic restrictions as of August 2008. Recipient   California State University, Northridge City   Northridge, CA Description   The College of Engineering and Computer Science (CECS) at California State University Northridge (CSUN), in collaboration with the College of Science and Mathematics (CSM), will acquire a Field Emission Scanning Electron Microscope (FESEM) with Energy Dispersive Spectroscopy (EDS). This system will provide the fundamental tools needed by faculty and students in the interdisciplinary Nanotechnology Undergraduate Education (NUE) program to investigate the complex phenomena that occur at the nanosize scale, and should advance the overall goal of bridging experimental and theoretical approaches to nanotechnology in research and teaching. The FESEM-NUE project will greatly enrich both colleges undergraduate curricula, increase early student exposure to nanotechnology, provide opportunities for student participation in sophisticated academic-industry research collaborations, and grant diverse students a competitive advantage for graduate studies and careers while meeting their financial needs. The project builds upon earlier curricular advances and student research engagement achieved with advanced computing equipment and sensitive microanalytic instrumentation acquired under a prior W.M. Keck Foundation grant. (Amount Awarded: $500,000) Recipient   Simmons College City   Boston, MA Description   The Undergraduate Laboratory Renaissance program will replace closed-end laboratory experiments with research-based laboratory work in each area of undergraduate science. A project based on a faculty member's research will form the basis for the semester's laboratory work, with teams of four students working on different aspects of the project. Upper-division majors will mentor students in research methodology and instrumental techniques. To coordinate research activity among several laboratory sections meeting each week, a Wiki-based laboratory notebook will be used to communicate results. When this research-based program is fully implemented, all students contemplating majors in chemistry, biochemistry, chemistry/pharmacy, and biology will participate in research beginning in the sophomore year following an introduction to research methodology during the spring of their first year.(Amount Awarded:$245,000) Recipient   University of California, Los Angeles City   Los Angeles, CA Description   UCLA has identified, as a critical next step in its Digital Humanities initiative, the creation of an undergraduate curriculum in the emergent field of digital cultural mapping. By integrating Geographic Information Systems into traditional methods of humanistic inquiry, digital cultural mapping uses informatics, spatial modeling, and time-space visualizations to create new tools and methods for investigating cultural, historical and social dynamics. Building on the tradition of a liberal arts education at UCLA, the curriculum will teach students critical reasoning, sound judgment, intellectual openness, and team-based problem solving. Students will learn to utilize, create, and evaluate the tools and technologies related to the geo-temporal web, a global information network in which location and information have merged together and datastreams are organized, processed, and viewed according to the parameters of space and time. The curriculum is unique because it draws faculty from seven different disciplines, bridges the resources of three research and teaching centers at UCLA, and uses new geo-technologies to develop collaborative, project-based approaches to learning with real-world applications. (Amount Awarded:$500,000) Civic and Community Recipient   Boys & Girls Clubs of Southwest County City   Temecula, CA Description   Since 2000, Southwest Riverside County's population has more than doubled to over 360,000. Because this rapid growth has outpaced available youth resources, the Boys & Girls Clubs of Southwest County is constructing a 15,000 square foot clubhouse to provide safe, neighborhood-based youth development programs for children and teens from low income families in the French Valley area. The facility will include a teen center, educational center, arts and crafts room, library, recreational and games room, computer lab, and multipurpose room, as well as office space and a conference room. The eight-acre site also contains sports fields, a swimming pool facility and playgrounds. (Amount Awarded:$300,000) Recipient   Downtown Women’s Center City   Los Angeles, CA Description   Women are the fastest growing segment of the local homeless population. With more than 16,000 women nightly without a home in Los Angeles, there is an urgent need for additional long-term housing and supportive services for this group. Downtown Women’s Center is responding to this need by renovating a six-story building that will increase permanent supportive housing; expand drop-in services; provide the first women's medical & mental health clinic on Skid Row, and create a social enterprise/job training program. (Amount Awarded: $500,000) Recipient   Shelter Partnership City   Los Angeles, CA Description   The project involves the rehabilitation of a 108,000 square foot warehouse in the City of Bell, where the S. Mark Taper Foundation Shelter Resource Bank operates. The Resource Bank distributes donated new goods to over 200 agencies/unique projects annually, providing them with essential items for both their operations and the clients they serve. For 19 years, the Federal government provided free rent for the warehouse. In July 2007, under the McKinney-Vento Homeless Assistance Act, ownership of the warehouse and accompanying six acres of property was transferred to Shelter Partnership at no cost. The warehouse complex was built in the early 1940s and has never been significantly rehabilitated or upgraded. Although safe, it does not meet today's building codes. This project will upgrade the major systems of the warehouse and also increase the Resource Bank’s storage capacity by more than one-third, ensuring sufficient potential for future growth. (Amount Awarded: $350,000) Recipient   Union Rescue Mission City   Los Angeles, CA Description   There is a startling lack of programs that are effectively freeing families from homelessness, and there are few transitional housing options for families in Los Angeles. Hope Gardens Family Center responds to this need. It is designed to provide a safe, healthy, and positive living environment away from Skid Row for up to 225 women and children. Through rehabilitative, educational, and life skills-building services, the program aims to transition families out of homelessness in a sustainable way and break the cycle of homelessness within these families. (Amount Awarded:$750,000) Health Care Recipient   Childrens Hospital Los Angeles City   Los Angeles, CA Description   Childrens Hospital Los Angeles (CHLA) has provided state-of-the-art medical care to children in a family-centered environment throughout its 107 year history. When the hospital's current inpatient facility was dedicated in 1968, it supported the best possible care available at that time. However, medical technology and practice significantly evolved over the last 40 years. Further, the current inpatient building does not meet the new state-mandated seismic requirements (SB 1953) that were passed after the 1994 Northridge earthquake. To continue offering the highest standards of medical excellence and quality care for children, it became imperative that the existing inpatient building be replaced. The seven-story, 460,000 square foot, 317 bed new hospital building will enable CHLA to expand key acute care services; incorporate advances in medical technology; enhance family-centered care; and exceed new seismic safety standards.(Amount Awarded:$1,000,000) Recipient   Eisner Pediatric & Family Medical Center City   Los Angeles, CA Description   The goal of the expansion/capital project is to increase high quality, affordable, and culturally competent healthcare for low-income women of all ages. Existing space will be renovated to create a dedicated home for the Women’s Health Center (WHC), which offers a wide range of comprehensive perinatal and gynecological services, including preconception, perinatal, and post-partum clinical care; health management and education classes; childbirth services (on-site at California Hospital Medical Center); high-risk pregnancy care; and family planning and reproductive health education. When operating at capacity, the WHC will be able to provide women-focused medical care to over 3,000 unduplicated clients every year, while improving patient flow in the adult and pediatric clinics and freeing exam rooms for anticipated growth in the demand for primary care. (Amount Awarded: $150,000) Precollegiate Education Recipient   Green Dot Public Schools City   Los Angeles, CA Description   The mission of Green Dot Public Schools is to transform public education in Los Angeles. The strategy is to restructure large, failing high schools into clusters of small, successful schools. Green Dot’s first School Transformation was launched around Jefferson Senior High School in South Los Angeles. In fall 2006, five new charter high schools were established around the campus. Animo Pat Brown was one of those new schools, opening in temporary quarters with its first class of 150 ninth graders. By fall 2009, it will be at full capacity with 560 students in grades nine through twelve. This project will construct a permanent facility in South Los Angeles that will help Animo Pat Brown solidify and increase its students' academic gains. (Amount Awarded: $400,000) Recipient   Unite-LA City   Los Angeles, CA Description   UNITE-LA promotes secondary school success and options for students in the Los Angeles Unified School District through the College & Career Success (C&CS) Network and C&CS Schools. This project engages a broad team of administrators, specialists, educators and corporate leaders to work collaboratively to directly support the small schools and small learning communities (SS/SLCs) being launched as part of reform efforts at four new and seven traditional high schools. UNITE-LA provides leadership development, staff training, and communication strategies. UNITE-LA also leverages resources from key partners to cultivate sustainable business-school partnerships to improve student achievement at more than 350 SS/SLCs. (Amount Awarded:$750,000) Early Learning Recipient   Information and Referral Federation of Los Angeles County City   San Gabriel, CA Description   211 LA County (211) operates the First 5 LA Parent Help-Line with trained specialists that provide information and referral services and support to parents and/or caregivers of children birth to five years of age. The Parent Help-Line serves an average of 3,000 to 4,000 low-income families monthly. In this three-year pilot project, 211 project staff will be trained to use the high-quality Parents' Evaluation of Developmental Status Screening tool (PEDS) with parents who already contact 211 for other information and express a concern about their child’s development. When a problem is flagged, the child will be referred for a more comprehensive assessment and, when needed, to services through a partnership with the Early Identification and Intervention Collaborative (EIIC), a network of more than 250 organizations serving children and families throughout the County. (Amount Awarded: $300,000) 2009 2008 2007 2006 2005 2004