Opening the Archives: Access to Information, Memory, and Justice Thirty Years After the End of the Brazilian Military Dictatorship
In 2012, Brazilian President Dilma Rousseff signed an Access to Information Law, establishing guidelines for declassifying documents and opening archives containing information about human rights violations committed by the Brazilian dictatorship (1964-85). She also appointed a Truth Commission to investigate the state’s involvement in torture and repression. Green has developed a joint project with a Brazilian historian to facilitate greater access to U.S. documents on Brazil for researchers in both countries. In conjunction with the Brazilian and U.S. National Archives, this collaborative team will coordinate a group of twelve Brown and two Brazilian students that will digitize and index U.S. State Department documents on Brazil from 1960 to 1980 that will appear on websites in Brazil and at Brown. The team will also identify documents for the Truth Commission’s investigations. This effort reinforces Brown’s reputation as the leading U.S. institution focusing on contemporary Brazilian history.
PI: James N. Green, Professor, History and Portuguese & Brazilian Studies
Co-PI: Sidnei Munhoz, State University of Maringá, Paraná Brazil
Solar Power by Optical Frequency Rectification with Plasmonic Concentrators Coupled to Junctions of Doped Mott Insulators
An alternative paradigm for the conversion of solar energy to electricity makes use of the collective electromagnetic nature of solar radiation instead of individual photons as conventional photovoltaic devices do. The electric field of sunlight is first intercepted by a nanoscale antenna, and then the oscillating electrical current is rectified into a useful DC current. Optical-frequency rectification – in effect a crystal radio that runs on visible light instead of radio waves – avoids altogether the mismatch between the photon energy and the semiconducting bandgap that limits the conversion efficiency of conventional photovoltaic cells. Solar rectification thus has the potential to create a cheaper and more efficient method for the exploitation of sunlight and could lead to a paradigm shift in solar technologies. This team will design and build prototype devices that combine plasmonic concentrators / antennas with novel rectifying junctions of doped Mott insulators to test the feasibility of the concept. A working device will be a compelling argument for external funding.
Domenico Pacifici, Assistant Professor, Engineering
Gang Xiao, Professor, Physics
Three-dimensional Traction Mapping Distinguish Neutrophils from Healthy and Septic Donors
Neutrophils are the most abundant white blood cell in the circulation and are among the first cells to response to an injury or infection; they are essential for health. Patients with decreased numbers of circulating neutrophils, or with inherited defects in neutrophil functions, are susceptible to opportunistic infections and have impaired wound healing. Efforts to study neutrophils under physiologically relevant settings have found that these cells are highly sensitive to physical and biochemical cues that regulate the magnitude of the cellular response to an insult. In order to translate laboratory findings to a better understanding of how the cells function in vivo, this Seed team will study neutrophils in a three dimensional setting rather than on standard 2D surfaces. This synergistic effort between laboratories in the Departments of Surgery at Rhode Island Hospital and the School Engineering will investigate neutrophil tractions in native 3D collagen gels and quantify cellular differences between healthy and septic cells.
Phosphatase Inhibitor Design – A Unique Possibility for Brown University
The specific and reciprocal relationship between kinases and phosphatases controls most biological processes. Thus, when the balance is disrupted, the result is often disease. To date, efforts to modulate phosphate signaling to treat these diseases have focused on inhibiting kinases. However, it has recently become evident that the exquisite regulation of phosphorylation signaling is driven by tyrosine and serine/threonine phosphatases, rather than by kinases. Thus, one of the fastest growing areas of research is to identify potent, specific inhibitors of phosphatases. The Seed team will combine expertise in biochemistry, structural biology, biophysics and synthetic organic chemistry in order to develop novel, potent inhibitors of phosphatases. This project aims to develop novel peptomimetic inhibitors of the ser/thr phosphatase PP1 using data from multiple PP1 holoenzyme structures, molecularly characterize and optimize inhibitors that target the tyr phosphatase PTP1B, and develop new, potent immunosuppressant drugs using data from the ser/thr phosphatase calcineurin and chemical scaffolds already shown to target calcineurin.
Paul G. Williard, Professor, Chemistry
Making Sense of the Data Windfall: New Statistical Approaches to Evolutionary Analyses of Gene Expression
Many studies analyze gene expression to identify genes that play a functional role in particular biological processes. New tools make it possible to inexpensively measure the expression of all genes in a tissue sample. These tools, as applied in current study designs, are proving to be blunt instruments that turn up thousands of candidate genes for a particular biological process, most of which are erroneous by-catch. There is critical need to sharpen the focus of gene expression studies so that they identify a smaller set of more relevant genes. We propose to address this by adding an evolutionary dimension to gene expression studies. It will then be possible to identify speciﬁc genes that have evolutionary shifts in expression that are correlated with evolutionary changes in biological processes of interest. The hurdle to this approach is that statistical methods have not yet been developed, implemented, and tested for evolutionary analyses of high-throughput gene expression data. This project assembles an interdisciplinary team to do exactly this, and leverages Brown’s strong investments in genome sequencing and high performance computing.
PIs: Casey W. Dunn, Assistant Professor, Ecology and Evolutionary Biology
Xi Luo, Assistant Professor, Biostatistics
Zhijin Wu, Associate Professor, Biostatistics
The Role of Electrical Coupling Between Mitral Cells in Olfactory Coding*
Smell is the primary sense used by many animals to find food and mates and to avoid predators. Olfactory deficits in people are associated with loss of appetite, anhedonia and depression, and olfactory dysfunction can be an early sign of neurodegenerative diseases. The basic mechanisms by which the brain discriminates odors are obscure. Odors are detected by sensory neurons in the nose that project to special neurons called mitral cells. Patterns of mitral cell activity are transformed by the brain into the percept of a smell. Some mitral cells are electrically coupled through structures called gap junctions, also known as electrical synapses. This Seed team combines multidisciplinary expertise and the techniques of mouse genetics, electrophysiology, and behavioral analyses to study the role of electrical synapses in olfactory coding.
The Role of the Right Hemisphere in Speech and Lexical Processing*
Past research using a variety of populations and research methodologies has produced conflicting findings on the role of the right hemisphere in speech and lexical (word) processing. This project research aims to examine this question by analyzing the effects of right hemisphere lesions on speech and lexical processing in the context of current models of the functional architecture of language using state-of-the-art behavioral paradigms, measures, and neuroimaging techniques. This novel approach will add to the continued and growing strength of the Brain Sciences at Brown by contributing to the breadth of approaches used and potentially opening new directions of research examining language functions of the right hemisphere using functional neuroimaging and the application of basic research findings (bench) to language rehabilitation (bedside). Additionally, it will add a new recruiting site at the Rhode Island Hospital.
PI: Sheila E. Blumstein, Professor, Cognitive Linguistic & Psychological Sciences
Co-PIs: Lynn Fanella, MRI Senior Research Technologist/Manager
Karen Furie, Chair and Professor, Neurology
Kathleen Kurowski, Assistant Professor, Cognitive Linguistic & Psychological Sciences (Research)
John Mertus, Assistant Professor, Cognitive Linguistic & Psychological Sciences (Research)
Carole Palumbo, Boston University School of Medicine and VA Boston Medical Center
Development of New Computational and Point of Care Platforms for HIV Drug Resistance**
HIV drug resistance is a major cause of treatment failure. The ability to identify drug resistance is important in patient care, and identification of specific drug resistance mutations can assist in efficient regimen design. Resistance testing, required in developed countries, is rarely used in resource-limited settings due to financial and infrastructure constraints. This is a major hurdle in the fight against HIV/AIDS since the vast majority of this pandemic is in resource limited settings. This project builds on preliminary research and a newly-developed microfluidic method termed SMART (Simple Method for Amplifying RNA Targets), to be integrated into a point of care chip platform, for drug resistance detection in resource limited settings. This Seed team will develop a computational platform for global analysis of position-specific pol sequence variation across geographic regions within HIV1 subtypes, develop a SMART Microfluidic Platform to amplify and detect drug resistance in a full-length HIV1 plasmid, and validate the platform in HIV-infected patient samples.
Sorin Istrail, Professor, Computer Science
Joseph Hogan, Professor, Biostatistics
*Made possible through a generous donation of an anonymous donor
**Special Seed award for translational research