Adrian Lee - US grants

Paul L. Richards
AST-0096933

Fully lithographed bolometer arrays using Voltage Biased Superconducting Bolometer (VSB) technology will be used to explore planar band-defining filters and RF multiplexers for use with antenna-coupled bolometers and to fabricate and test prototype arrays of antenna coupled hot-electron bolometers with RF multiplexers and filters, and fabricate and test 32 x 32 absorber-coupled focal-plane bolometer arrays. Also work to explore integrating these arrays with a recently developed readout multiplexer that uses only a single SQUID per row of detectors will continue.

This technology will provide new high sensitivity detectors in the currently unexplored but astrophysically interesting sub-millimeter part of the electromagnetic spectrum.
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AST-0138348
Lee, Adrian

A millimeter wave bolometric receiver will be built for the 12-meter diameter Atacama Pathfinder Experiment (APEX) telescope in transition with Max Planck Institute for Radioastronomy (MPIfR) in Bonn, Germany. This receiver is a 300-element bolometric receiver for observations at 150 and 217 GHz. The bolometers will be horn-coupled, spider-web devices with superconducting transistor-edge sensors (TES) each using SQUID ammeter readout configured for 1024 elements. This receiver will be used to discover and study galaxy clusters via the thermal Sunyaev-Zel'dovich (SZ) effect at millimeter wavelengths. Data recorded with optical and x-ray measurements, when correlated with data recorded by this receiver promise to 1. reveal the formation history of galaxies, 2. Probe the nature of dark energy by measuring its equation of state, and 3. measure cosmological parameters including the mass energy density and the Hubble constant.
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AST-0352992 -- Richards, Caltech

Planar-antenna-coupled superconducting bolometer systems for observations at submillimeter and millimeter wavelengths will be developed. Antenna-coupled arrays have the potential to greatly increase the efficiency of observations, opening the door to new science objectives. The objectives are to fully characterize the prototype antenna-coupled bolometer design; design and test wide-band dual-polarization antennas; develop an RF "channelizer" that splits the signal from a single antenna into multiple bands; and develop RF switches using Micro-Electro-Mechanical Systems techniques for polarization, phase, and load switches. The bolometer development may have impact in x-ray calorimeters, UV-IR spectrometers, and THz concealed weapons detection systems.

AST 0618398
Lee

Observations of Cosmic Microwave Background (CMB) polarization are a powerful probe of cosmology and will eventually probe the standard model of physics at ultrahigh energy. With this award, Dr. Adrian Lee, University of California at Berkeley, will lead a new project called POLARBEAR (POLARization of the Background Radiation) which will use a dedicated telescope equipped with a powerful 1,200-bolometer array receiver to produce maps of CMB polarization with unprecedented accuracy. The most exciting possibility is that POLARBEAR will detect the signature of gravitational waves from the end of the inflationary period, 10-38 seconds after the Big Bang. If detected, these signals will provide an independent verification of the inflationary paradigm and test specific models for inflation.

Another important scientific motivation is to characterize the gravitational lensing of the CMB
polarization. An accurate lensing measurement will yield constraints on Dark Energy. POLARBEAR can verify, or rule out, models with a strongly time-dependent Dark Energy equation of state w. In fact, POLARBEAR can provide information on w", the time derivative of w, which is comparable and complementary to that from a space-based supernovae search. The lensing signal is also sensitive to neutrino masses because massive neutrinos act as "hot" dark matter changing the formation of the lensing large scale structure.

POLARBEAR introduces unprecedented levels of instrumental sensitivity and control of systematic
errors. The high sensitivity is achieved with an array of planar-antenna-coupled Transition-Edge
Sensor (TES) bolometers operated at 250 mK. Dr. Lee and his colleagues have built and conducted tests of prototypes of these arrays. POLARBEAR's final configuration will include 1,200 bolometers distributed among three frequency bands at 90, 150, and 220 GHz.

Members of the collaboration have played key roles on many of the best CMB experiments to
date. They are also playing a key role in bringing the next generation of large TES focal plane
instruments. These experiments will be reaching maturity as POLARBEAR starts, and the collaboration members will be focused on building POLARBEAR. There will be significant international funding contributions from Canada on the readout electronics, from the UK on optical filters, and from France and the UK on data analysis.

POLARBEAR is the most ambitious CMB polarization experiment to date, and it will explore the
ultimate limit of ground-based CMB polarimetry. POLARBEAR's unique combination of high sensitivity and stringent control of systematic errors will result in a search for inflationary gravitational waves over most of the experimentally accessible range.

POLARBEAR will explore new technologies and methods that will carry forward to future CMB experiments such as NASA's CMBPOL mission. At UCSD, the team will connect POLARBEAR with the 'TRITONCAM' project that uses a radio telescope and polarimeter to teach physics to San Diego high school students.

AST-0709497
Lee

This project will carry out a deep blind survey for galaxy clusters via the Sunyaev-Zel'dovich effect (SZE), using the Atacama Pathfinder EXperiment (APEX) telescope and a 320-element superconducting bolometer array. This involves a close collaboration with the Max Planck Institute for Radioastronomy (MPIfR, Bonn, Germany). A high-quality catalog of SZE-selected clusters over a broad range of redshifts will provide deep insight into structure formation, high accuracy measurements of cosmological parameters, and a characterization of the dark energy equation of state. This dark energy measurement is complementary in parameter degeneracies to other types, such as those using supernovae. SZE surveys are expected to have a cleaner selection function that extends to higher redshift than optical and X-ray techniques. Hundreds of galaxy clusters will be detected, with as many as one hundred at redshift one or greater.

APEX is a fully operational 12-meter diameter on-axis Cassegrain telescope sited at 16,700 ft on the Chajnantor plateau in Chile. It was built by a consortium of the MPIfR, the European Southern Observatory (ESO), and the Swedish Onsala Space Observatory. The SZE survey will use at least one month of telescope time per year, and this allotment may increase. The receiver has had a successful engineering run and been upgraded to the observational configuration. This program leverages the substantial investments in receiver development and deployment, in superconducting transition edge sensors (TES), and in construction and operation of the telescope, by NSF and by the various national and international partners.

The planned calibration of the mass to SZE flux relation by APEX in an early emphasis project will be critical for interpreting the large cluster samples expected from future surveys by other telescopes. This will be carried out using multi-wavelength data from a variety of experiments all looking at the same patch of sky, and comparing the SZE data against measurements using optical weak lensing, optical galaxy counts, X-ray flux, and velocity dispersions. The work will cement relations across a strong international team. In addition, the detector development work has widespread implications for astronomy, other physics communities, and homeland security.

DESCRIPTION (provided by applicant): Insulin receptor substrates 1 and 2 (IRSs) are large adaptor proteins downstream of insulin-like growth factor-I receptor (IGF-IR) which modulate normal growth, metabolism, survival, and differentiation. Recent studies have shown that IRSs can interact with, and are functionally required for the transforming ability of many oncogenes, and IRSs are elevated and hyperactive in many human tumors including breast cancer. The long-term goal of these studies is to understand the role of inuslin receptor substrates (IRSs) in breast cancer, and determine if they may have a role in predicting response to anti-IGF-IR inhibitors. To better understand the role of IRSs in mammary gland development and breast cancer, in the last funding period, we created and studied several novel in vitro and in vivo models of IRS action. Using IRS-null mice we found that IRSs are required for embryonic mammary bud formation and for maximal lactation. Using human immortalized MCF-10A cells we showed that overexpression of IRSs disrupted formation of acini by altering polarity, proliferation, and survival. Finally, we generated transgenic mice with mammary-specific overexpression of either IRS-1 or IRS-2 with both lines of mice displaying progressive mammary hyperplasia, tumors, and metastasis. Intriguingly, studies from others using IRS-2-null mice have shown that only IRS-2 is required for mammary tumor metastasis. These studies have raised three fundamental questions: 1) How do IRSs modulate mammary cell polarity, transformation, and tumorigenesis? 2) Why do both IRS-1 and IRS-2 cause transformation, but only IRS-2 is required for metastasis? 3) Are IRSs important in breast cancer progression and prognosis, and can levels and/or activity predict response to anti-IGF-IR inhibitors? We will address these questions with the following specific aims: 1) Do both IRS-1 and IRS-2 disrupt morphogenesis of MCF-10A acini via aPKC mediated disruption of the polarity complex, and promote proliferation and survival downstream of IGF-IR? 2) Does IRS-2 utilize a unique bi-directional positive regulation of NF-?B activity to modulate migration, invasion, and metastasis? 3) Are IRSs important in breast cancer progression and prognosis, and can they be used as predictors of response to anti-IGF-IR therapy? The long-term impact of these studies will be a better understanidng of IRS action in breast cancer, and a possible new biomarker for predicting response to IGF-IR inhibitors in breast cancer.

This program will use the newly constructed POLARBEAR 3.5-meter-diameter off-axis telescope near ALMA in Chile for observations of cosmic microwave background (CMB) polarization, in order to measure or constrain primordial gravitational B-modes and CMB lensing. The data will be used to map large scale structure and constrain neutrino masses and early dark energy models. The award will fund both operation of the telescope and production of the scientific results.

Broader impacts of the work include training of graduate students and a postdoc, collaboration with Chilean and Japanese scientists, and outreach to low-income and under-represented high school students.

The most successful model of the universe involves a period of immense expansion during the first small fraction of a second following the Big Bang. This "phase-change" in the early universe explains a number of key observations, including the extreme flatness of the universe, the very similar properties of causally unrelated regions of the observable universe, and the lack of magnetic monopoles. An important prediction of inflation is the "handedness" of polarization imprinted by gravitational waves that are thought to have existed at the time of the last photon scattering. Searching for this "B-mode" polarization signal is a fundamental test of inflation, diagnostic of the energy scale over which the phase change operated, and one of the key science themes identified for the next decade by the ASTRO2010 survey New Worlds, New Horizons in Astronomy and Astrophysics.

Dr. Adrian Lee of the University of California Berkeley and collaborators elsewhere within the U.S. as well as in Canada, United Kingdom, and Japan plan an experiment to detect and explore for the first time the B-mode polarization using a dedicated radio antenna high on the Atacama Plateau in Chile and a state-of-the-art 7,588 pixel bolometer array to map the sky at the dual frequencies of 150 and 220 GHz with higher sensitivity and an order of magnitude faster than current experiments. The project, POLARBEAR-2, is very well motivated scientifically and equally well justified on a technical and management footing by the pilot project POLARBEAR-1, now complete and obtaining initial data at the Chilean site. Technical developments made through the project will be important at other wavelength regions of astronomical detection, including the sub-mm. Postdoctoral and student involvement is included in important elements of the development and testing, continuing the strong tradition of training in the hardware and techniques of radio astronomy at U.C. Berkeley.

Funding for the development of the POLARBEAR-2 project is being provided by NSF's Division of Astronomical Sciences through its Advanced Technologies and Instrumentation program.

Project Summary / Abstract In order to dynamically follow different conversations in a crowded environment, we must constantly direct attention to the auditory signal of interest and segregate sounds that originated from other sources. Normal- hearing listeners can achieve this task seamlessly, but hearing-impaired listeners, cochlear implant users, and individuals with (central) auditory processing disorders often find communicating in this everyday acoustic environment challenging. The long-term objective of this research is to characterize the cortical dynamics associated with different aspects of auditory attention and to incorporate these brain signals in a next- generation hearing assistive device that helps account for the listener's attentional focus. The current project is built on the hypothesis that there are distributed cortical regions that coordinate top-down and bottom-up auditory attention, and that these regions are functionally coupled to the auditory sensory areas differently depending on the task at hand. The brain dynamics associated with auditory attention are currently not well understood, and thus a necessary first step to achieve our long-term objective is to study the attentional network in normal-hearing listeners. The specific aims of this project seek to identify differences between the cortical regions recruited for attention based on spatial and non-spatial features (Aim 1), as well as how the rest of the cortex compensates when the peripheral auditory signal is degraded by simulating the reduction in spectrotemporal acuity experienced by listeners with hearing impairments and cochlear implant users (Aim 2). Furthermore, we propose to take a systems-level approach and investigate how other cortical regions communicate with the auditory sensory areas in order to coordinate switching and maintenance of attention in a crowded acoustical scene (Aim 3). Our proposal emphasizes designing behavioral paradigms that bridge the gap between psychoacoustics and neuroimaging research, thereby addressing how different regions of the cortex act in concert to aid us in communicating in everyday settings.

The POLARBEAR experiment measures polarized fluctuations in the Cosmic Microwave Background (CMB) to search for the signature of gravitational waves from inflation, potentially opening a window on the universe a fraction of a second after the Big Bang. This is a major quest of current physics and astronomy and has broad implications for our understanding of the origin and history of the universe. AST has previously funded the construction, commissioning, and initial operations of the first POLARBEAR 3.5m-diameter telescope at the Atacama desert site near ALMA in Chile. The current award will support commissioning and operations of a second telesope under partnership with the Simons foundation and other collaborating institutions in the US, Japan, Canada, and the UK. The award will support advanced traning for students in instrumentation and facility development. Other broader impacts include educational programs for K-12 students and the general public.

Science goals in addition to B-mode gravitational waves include a search for massive neutrinos, a map of large scale structure in the universe via gravitational lensing, and constraints on the primordial helium abundance and the effective number of relativistic species.

Abstract: Breast and Ovarian Cancer Program (BOCP) The mission of the Breast and Ovarian Cancer Program (BOCP), a newly established Program being proposed in this UPCI Cancer Center Support Grant renewal, is to reduce the incidence and death from women's cancer with a focus on breast and ovarian malignancies. This mission is achieved through the development and fostering of basic, translational, and clinical research in breast and ovarian cancer and aimed at translating novel discoveries into improved patient care. The BOCP has four main research themes: 1) basic cancer biology, 2) diagnostic and prognostic markers, 3) prevention, and 4) molecular therapeutics. The BOCP specific aims are to: 1) investigate mechanisms of cancer initiation and progression, 2) identify and validate new diagnostic and prognostic markers, 3) examine the role of tumor evolution and heterogeneity in progression and response to therapy, 4) discover the phenotypic and genotypic dependencies of metastatic cancer, and 5) translate knowledge of the biology into personalized prevention and treatment. The BOCP has 42 members representing 12 academic departments and 3 schools of the University of Pittsburgh. Based upon a retrospective analysis of historical data from January 2010 to April 2014, BOCP members authored or co- authored 517 cancer-related publications, of which 31% resulted from intra-programmatic and 30% from inter- programmatic collaborations. Approximately 54% of the papers represent collaborations with external investigators. Research in the BOCP is supported by an NCI Specialized Program of Research Excellence (SPORE) in Ovarian Cancer shared with Roswell Park Cancer Institute (RPCI), as well as individual federal grants, foundation awards, and philanthropy. BOCP members currently receive a total of $8.2 M in annual direct funding, including $2.6 M from the NCI and $2.1 M in other peer-reviewed grant support. A highly collaborative and interactive group, BOCP members meet regularly at work-in-progress meetings, journal clubs, and a yearly retreat. In addition, the BOCP forges relationships with other programs to enhance the multi-disciplinary nature of breast and ovarian cancer research at UPCI. UPCI support, including Clinical Protocol and Data Management and Shared Resources, specifically the Animal Facility, Biostatistics Facility, Cancer Bioinformatics Services, Cancer Genomics Facility, Cancer Pharmacokinetics and Pharmacodynamics Facility, Cancer Proteomics Facility, Cell and Tissue Imaging Facility, Chemical Biology Facility, Cytometry Facility, Immunological Monitoring and Cellular Products Laboratory, In Vivo Imaging Facility, Investigational Drug Services, and Tissue and Research Pathology Services facilitates and enhances BOCP research.

Despite receiving normal audiological assessments, some listeners still complain to clinicians that they struggle to hear, particularly in noisy or crowded environments. However, systematic investigations into how the brain processes sound (and how it can go wrong) are lacking. The goal of this funded project is to apply novel statistical approaches to study patterns of activity in the brain while it processes sound in complex situations like when listening in a multi-talker environment.

A wide variety of behavioral and electrophysiological responses will be collected under several different types of auditory stimulation. Behavioral data and physiological measures of brainstem response will be used to characterize individuals' hearing health in both monaural and binaural pathways, providing complementary information to their cortical magneto- and electroencephalography (M-EEG) responses during similar auditory tasks. Auditory attentional network connectivity will also be analyzed, to account for the neural underpinnings of aspects of auditory dysfunction such as the inability to maintain or switch attention between speakers. Using computationally-driven statistical approaches, flexible graphical model-based representations of high-dimensional time series will be learned, in order to characterize the auditory attentional network based on collected M-EEG data. Specifically, two computational aims will be tackled: 1) Construct Bayesian models to characterize dynamical cortical interactions at different spatial resolutions and 2) Develop models that infer connectivity structure at different canonical cortical rhythmic bands. This research program leverages the complementary expertise of the two investigators, bringing together auditory behavioral and systems neuroscience, with flexible and scalable statistical time series modeling approaches. Temporal structure is often ignored in big data analyses as well as in systems neuroscience, and this funded research will directly address this shortcoming by using a high-dimensional set of temporally continuous neural data. The cortical network discovered by this approach will enable neuroscientists to better understand the variability inherent in the auditory attentional network across both task types and individual differences in listening abilities.

Biomedical researchers have an increasing ability to comprehensively interrogate cell and molecular biology, for example with advanced imaging and next-generation sequencing. These techniques are producing datasets of increasing size and complexity and necessitate high-performance computing for biomedical researchers. Results from these studies are rapidly changing our understanding of normal development, our taxonomy of disease, and ultimately will enable precision medicine. Recognizing the importance of data science in precision medicine, the Institute for Precision Medicine (IPM) and the University of Pittsburgh invested in a high-throughput computing cluster (HTC), with infrastructure suited for memory-intensive and IO-intensive genomic and bioinformatic operations, and an education program dedicated to enabling computing for health science researchers. The HTC is located in the Center for Research Computing (CRC), a secure and centralized enterprise facility providing computing resources to the whole of the University. The CRC provides a scalable model for research computing with expertise in use and monitoring of advanced computing. In 2015, the HTC was installed with 16 nodes (256 cores). Usage of the HTC grew rapidly (2016 - 0.5M core-hours to 2019 ? 3.1M core-hours), and despite the addition of computing nodes in 2017 (4 nodes), 2018 (4 nodes) and 2019 (16 nodes) the system often runs at capacity. Furthermore, the nodes have reached their useable lifespan. In this application, we are requesting funds to replace the HTC cluster and increase computing availability with a new cluster of 20 CPU nodes (960 cores) and 8 GPU cards, 2 CPU nodes as application servers, and 1.2 PB of BeeGFS storage, all linked by Infiniband HDR networking. The new HTC cluster is dedicated to NIH-funded research in biomedical science including medicine, pediatrics, cancer, immunology, and other areas. To assist health science researchers, the IPM, CRC and the health science library system (HSLS) support institution-wide licenses from numerous analysis and bioinformatics software suites, several of which are installed on the HTC server. Importantly, HSLS and CRC provide education outreach through workshops for command line tools, R for genomics and software suites. Researchers using software suites such as CLC Genomics, Open OnDemand, or command line can transparently migrate data and perform analysis on the multi-core HTC. IPM collaboration with the CRC ensures that the new HTC cluster will be operated in the most cost-effective and efficient manner and will be of high value to health sciences researcher performing NIH-supported research. This collaborative effort significantly reduces barriers for biomedical researchers needing to perform computational research.