A5043449753- Advanced Fluorescence Microscopy Techniques
- Parallel Computing and Optimization Techniques
- Cell Image Analysis Techniques
- Photoacoustic and Ultrasonic Imaging
- Embedded Systems Design Techniques
- Photoreceptor and optogenetics research
- Distributed and Parallel Computing Systems
- Advanced Electron Microscopy Techniques and Applications
- Neural dynamics and brain function
- Distributed systems and fault tolerance
- Formal Methods in Verification
- Logic, programming, and type systems
- Pluripotent Stem Cells Research
- Molecular Biology Techniques and Applications
- Advanced Data Storage Technologies
- Neuroscience and Neuropharmacology Research
- Optical Coherence Tomography Applications
- Algorithms and Data Compression
- Advanced Memory and Neural Computing
- Advanced Malware Detection Techniques
- Security and Verification in Computing
- Solid-state spectroscopy and crystallography
- Single-cell and spatial transcriptomics
- Real-Time Systems Scheduling
- Optical Imaging and Spectroscopy Techniques
Stanford University
2019-2024
Yale University
2024
ETH Zurich
1988-2023
Janelia Research Campus
2017-2023
Howard Hughes Medical Institute
2017-2023
Board of the Swiss Federal Institutes of Technology
2016-2022
ORCID
2020
Helix (United States)
2018-2019
Karlsruhe Institute of Technology
2011-2018
Carnegie Mellon University
2011
Abstract The fluorescent glutamate indicator iGluSnFR enables imaging of neurotransmission with genetic and molecular specificity. However, existing variants exhibit low in vivo signal-to-noise ratios, saturating activation kinetics exclusion from postsynaptic densities. Using a multiassay screen bacteria, soluble protein cultured neurons, we generated improved ratios kinetics. We developed surface display constructs that improve iGluSnFR’s nanoscopic localization to postsynapses. resulting...
Hematopoietic cell transplantation after myeloablative conditioning has been used to treat various genetic metabolic syndromes but is largely ineffective in diseases affecting the brain presumably due poor and variable myeloid incorporation into central nervous system. Here, we developed characterized a near-complete homogeneous replacement of microglia with bone marrow cells mice without need for manipulation donor or host. The high chimerism resulted from competitive advantage scarce...
Abstract Information within the brain travels from neuron to across billions of synapses. At any given moment, only a small subset neurons and synapses are active, but finding active in tissue has been technical challenge. Here we introduce SynTagMA tag user-defined time window. Upon 395–405 nm illumination, this genetically encoded marker activity converts green red fluorescence if, it is bound calcium. Targeted presynaptic terminals, preSynTagMA allows discrimination between silent axons....
Green-to-red photoconvertible fluorescent proteins (pcFPs) are powerful tools for super-resolution localization microscopy and protein tagging. Recently, they have been found to undergo efficient photoconversion not only by the traditional 400-nm illumination but also an alternative method termed primed conversion, employing dual wavelength with blue far-red/near-infrared light. Primed conversion has reported Dendra2 its mechanism remained elusive. Here, we uncover molecular of reporting...
Abstract The fluorescent glutamate indicator iGluSnFR enables imaging of neurotransmission with genetic and molecular specificity. However, existing variants exhibit saturating activation kinetics are excluded from post-synaptic densities, limiting their ability to distinguish synaptic extrasynaptic glutamate. Using a multi-assay screen in bacteria, soluble protein, cultured neurons, we generated novel improved signal-to-noise ratios. We also developed surface display constructs that improve...
Writing concurrent applications is extremely challenging, not only in terms of producing bug-free and maintainable software, but also for enabling developer productivity. In this article we present the Æminium concurrent-by-default programming language. Using programmers express data dependencies rather than control flow between instructions. Dependencies are expressed using permissions, which used by type system to automatically parallelize application. The approach provides a modular...
In pharmacological research the development of promising lead compounds requires a detailed understanding dynamics disease progression. However, for many diseases, such as kidney fibrosis, gaining complex real-time, multi-dimensional analysis diseased and healthy tissue. To allow studies with increased throughput we established dextran hydrogel-based in vitro 3D co-culture model fibrosis aimed at discovery modulating epithelial/mesenchymal crosstalk. This platform mimics simplified...
The ability of fluorescent proteins (FPs) to fold robustly is fundamental the autocatalytic formation chromophore. While importance tertiary protein structure well appreciated, impact individual amino acid mutations for FPs often not intuitive and requires direct testing. In this study, we describe engineering a monomeric photoswitchable FP, moxMaple3, use in oxidizing cellular environments, especially eukaryotic secretory pathway. Surprisingly, point mutation replace cysteine substantially...
Third-harmonic generation microscopy is a powerful label-free nonlinear imaging technique, providing essential information about structural characteristics of cells and tissues without requiring external labelling agents. In this work, we integrated recently developed compact adaptive optics module into third-harmonic microscope, to measure correct for optical aberrations in complex tissues. Taking advantage the high sensitivity process material interfaces thin membranes, along with 1,300-nm...
Abstract Green‐to‐red photoconvertible fluorescent proteins (pcFPs) are powerful tools for super‐resolution localization microscopy and protein tagging. Recently, they have been found to undergo efficient photoconversion not only by the traditional 400‐nm illumination but also an alternative method termed primed conversion, employing dual wavelength with blue far‐red/near‐infrared light. Primed conversion has reported Dendra2 its mechanism remained elusive. Here, we uncover molecular of...
Linear permissions have been proposed as a lightweight way to specify how an object may be aliased, and whether those aliases allow mutation. Prior work has demonstrated the value of for addressing many software engineering concerns, including information hiding, protocol checking, concurrency, security, memory management.
Access permissions (permissions for short) are a lightweight way to specify how an object may be aliased and whether aliases allow mutation. Prior work has demonstrated the value of addressing many software engineering concerns, including information hiding, protocol checking, concurrency, security, memory management.
Accurate lineage reconstruction of mammalian pre-implantation development is essential for inferring the earliest cell fate decisions. Lineage tracing using global fluorescence labeling techniques complicated by increasing density and rapid embryo rotation, which hampers automatic alignment accurate tracking obtained four-dimensional imaging data sets. Here, we exploit advantageous properties primed convertible fluorescent proteins (pr-pcFPs) to simultaneously visualize green photoconverted...
ABSTRACT Information within the brain travels from neuron to across synapses. At any given moment, only a few synapses billions will be active and are thought transmit key information about environment, behavior being executed or memory recalled. Here we present SynTagMA, which marks ~2 s time window. Upon violet illumination, genetically expressed tag converts green red fluorescence if bound calcium. Targeted presynaptic terminals, preSynTagMA allows discrimination between silent axons....
Abstract Understanding complex biological systems requires visualizing structures and processes deep within living organisms. We developed a compact adaptive optics module incorporated it into two- three-photon fluorescence microscopes, to measure correct tissue-induced aberrations. resolved synaptic in cortical subcortical areas of the mouse brain, demonstrated high-resolution imaging neuronal somatosensory-evoked calcium responses spinal cord at unprecedented depths vivo.
Register allocation is one of the most time-consuming parts compilation process. Depending on quality register allocation, a large amount shuffle code to move values between registers generated. In this paper, we propose processor architecture extension provide file permutations by which can be implemented more efficiently. We present compiler support utilize extension, an evaluation regarding performance and time using SPEC CINT2000 benchmark, as well analysis area frequency overhead our...