3,986 results on '"Cohen, Bruce"'
Search Results
52. Fluorescence activation mechanism and imaging of drug permeation with new sensors for smoking-cessation ligands.
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Nichols, Aaron L, Blumenfeld, Zack, Fan, Chengcheng, Luebbert, Laura, Blom, Annet EM, Cohen, Bruce N, Marvin, Jonathan S, Borden, Philip M, Kim, Charlene H, Muthusamy, Anand K, Shivange, Amol V, Knox, Hailey J, Campello, Hugo Rego, Wang, Jonathan H, Dougherty, Dennis A, Looger, Loren L, Gallagher, Timothy, Rees, Douglas C, and Lester, Henry A
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Animals ,Humans ,Mice ,Alkaloids ,Azepines ,Azocines ,Quinolizines ,Nicotinic Agonists ,Ligands ,Smoking Cessation ,Fluorescence ,Heterocyclic Compounds ,4 or More Rings ,biosensors ,iDrugSnFRs ,inside-out pharmacology ,mouse ,neuroscience ,nicotine ,nicotinic agonists ,pharmacokinetics ,Brain Disorders ,Tobacco Smoke and Health ,Tobacco ,Substance Misuse ,Drug Abuse (NIDA only) ,Neurosciences ,Cancer ,Generic health relevance ,Good Health and Well Being ,Mouse ,Biochemistry and Cell Biology - Abstract
Nicotinic partial agonists provide an accepted aid for smoking cessation and thus contribute to decreasing tobacco-related disease. Improved drugs constitute a continued area of study. However, there remains no reductionist method to examine the cellular and subcellular pharmacokinetic properties of these compounds in living cells. Here, we developed new intensity-based drug-sensing fluorescent reporters (iDrugSnFRs) for the nicotinic partial agonists dianicline, cytisine, and two cytisine derivatives - 10-fluorocytisine and 9-bromo-10-ethylcytisine. We report the first atomic-scale structures of liganded periplasmic binding protein-based biosensors, accelerating development of iDrugSnFRs and also explaining the activation mechanism. The nicotinic iDrugSnFRs detect their drug partners in solution, as well as at the plasma membrane (PM) and in the endoplasmic reticulum (ER) of cell lines and mouse hippocampal neurons. At the PM, the speed of solution changes limits the growth and decay rates of the fluorescence response in almost all cases. In contrast, we found that rates of membrane crossing differ among these nicotinic drugs by >30-fold. The new nicotinic iDrugSnFRs provide insight into the real-time pharmacokinetic properties of nicotinic agonists and provide a methodology whereby iDrugSnFRs can inform both pharmaceutical neuroscience and addiction neuroscience.
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- 2022
53. Immunotargeting of Nanocrystals by SpyCatcher Conjugation of Engineered Antibodies
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Pedroso, Cassio CS, Mann, Victor R, Zuberbühler, Kathrin, Bohn, Markus-Frederik, Yu, Jessica, Altoe, Virginia, Craik, Charles S, and Cohen, Bruce E
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Biological Sciences ,Biomedical and Clinical Sciences ,Industrial Biotechnology ,Bioengineering ,Breast Cancer ,Cancer ,Nanotechnology ,Humans ,Receptors ,Urokinase Plasminogen Activator ,Antibodies ,Nanoparticles ,Cell Membrane ,Quantum Dots ,Urokinase-Type Plasminogen Activator ,bioconjugation ,upconverting nanoparticles ,quantum dots ,antibodies ,uPAR ,cancer cells ,receptor trafficking ,Nanoscience & Nanotechnology - Abstract
Inorganic nanocrystals such as quantum dots (QDs) and upconverting nanoparticles (UCNPs) are uniquely suited for quantitative live-cell imaging and are typically functionalized with ligands to study specific receptors or cellular targets. Antibodies (Ab) are among the most useful targeting reagents owing to their high affinities and specificities, but common nanocrystal labeling methods may orient Ab incorrectly, be reversible or denaturing, or lead to Ab-NP complexes too large for some applications. Here, we show that SpyCatcher proteins, which bind and spontaneously form covalent isopeptide bonds with cognate SpyTag peptides, can conjugate engineered Ab to nanoparticle surfaces with control over stability, orientation, and stoichiometry. Compact SpyCatcher-functionalized QDs and UCNPs may be labeled with short-chain variable fragment Ab (scFv) engineered to bind urokinase-type plasminogen activator receptors (uPAR) that are overexpressed in many human cancers. Confocal imaging of anti-uPAR scFv-QD conjugates shows the antibody mediates specific binding and internalization by breast cancer cells expressing uPAR. Time-lapse imaging of photostable scFv-UCNP conjugates shows that Ab binding causes uPAR internalization with a ∼20 min half-life on the cell surface, and uPAR is internalized to endolysosomal compartments distinct from general membrane stains and without significant recycling to the cell surface. The controlled and stable conjugation of engineered Ab to NPs enables targeting of diverse receptors for live-cell study of their distribution, trafficking, and physiology.
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- 2021
54. Surface-Sensitive Photon Avalanche Behavior Revealed by Single-Avalanching-Nanoparticle Imaging
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Kwock, Kevin WC, Lee, Changhwan, Teitelboim, Ayelet, Liu, Yawei, Yao, Kaiyuan, Alam, Sardar B, Cohen, Bruce E, Chan, Emory M, and Schuck, P James
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Nanotechnology ,Bioengineering ,Chemical Sciences ,Engineering ,Technology ,Physical Chemistry - Abstract
Avalanching nanoparticles (ANPs) are a new class of lanthanide-based upconverting material demonstrating steep optical nonlinearities with the potential to advance applications ranging from subwavelength bioimaging to neuromorphic computing, nanothermometry, and pressure transduction. Here, we use single-nanocrystal imaging to uncover design-dependent heterogeneity in ANP threshold intensity (Ith). Quantitative comparisons between distributions of Ith and ANP shell properties reveal correlations between mean Ith values, histogram widths, and nanocrystal shell thickness. Evaluating avalanching behaviors using an established model of shell-dependent surface energy transfer shows that variations in shell thickness-and the resultant energy transfer through the shell to the surface and environment-are likely the primary contributor to ANP-to-ANP Ith heterogeneity. Further, nanocrystals with an ∼6 nm average shell thickness show Ith heterogeneity beyond the extent expected from statistical measurements of shell size and variability using transmission electron microscopy (TEM). These results provide a principal guide for the design and application of ANPs to environmental sensing.
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- 2021
55. EVAP: A two-photon imaging tool to study conformational changes in endogenous Kv2 channels in live tissues.
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Thapa, Parashar, Stewart, Robert, Sepela, Rebecka J, Vivas, Oscar, Parajuli, Laxmi K, Lillya, Mark, Fletcher-Taylor, Sebastian, Cohen, Bruce E, Zito, Karen, and Sack, Jon T
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Animals ,Carrier Proteins ,Hippocampus ,Neurons ,Rats ,Shab Potassium Channels ,Spider Venoms ,Neurosciences ,Bioengineering ,2.1 Biological and endogenous factors ,Physiology ,Medical Physiology - Abstract
A primary goal of molecular physiology is to understand how conformational changes of proteins affect the function of cells, tissues, and organisms. Here, we describe an imaging method for measuring the conformational changes of the voltage sensors of endogenous ion channel proteins within live tissue, without genetic modification. We synthesized GxTX-594, a variant of the peptidyl tarantula toxin guangxitoxin-1E, conjugated to a fluorophore optimal for two-photon excitation imaging through light-scattering tissue. We term this tool EVAP (Endogenous Voltage-sensor Activity Probe). GxTX-594 targets the voltage sensors of Kv2 proteins, which form potassium channels and plasma membrane-endoplasmic reticulum junctions. GxTX-594 dynamically labels Kv2 proteins on cell surfaces in response to voltage stimulation. To interpret dynamic changes in fluorescence intensity, we developed a statistical thermodynamic model that relates the conformational changes of Kv2 voltage sensors to degree of labeling. We used two-photon excitation imaging of rat brain slices to image Kv2 proteins in neurons. We found puncta of GxTX-594 on hippocampal CA1 neurons that responded to voltage stimulation and retain a voltage response roughly similar to heterologously expressed Kv2.1 protein. Our findings show that EVAP imaging methods enable the identification of conformational changes of endogenous Kv2 voltage sensors in tissue.
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- 2021
56. New sub equipment & training will save lives
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Cohen, Bruce A., CAPT
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SUBMARINES - Safety Measures ,WARSHIPS - Safety Measures ,ESCAPE EQUIPMENT ,ACCIDENTS, MARINE - Safety Measures ,SHIPS - Emergency Procedures - Abstract
illus
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- 2003
57. The need for evidence-based updating of ICD and DSM models of psychotic and mood disorders
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Cohen, Bruce M. and Öngür, Dost
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- 2023
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58. Henry Johnson (ed.) (2010) Many voices : music and national identity in Aotearoa/New Zealand
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Cohen, Bruce M. Z.
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- 2012
59. Still Life
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Cohen, Bruce
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- 2012
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60. American Academy of Neurology Telehealth Position Statement
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Hatcher-Martin, Jaime M, Busis, Neil A, Cohen, Bruce H, Wolf, Rebecca A, Jones, Elaine C, Anderson, Eric R, Fritz, Joseph V, Shook, Steven J, and Bove, Riley M
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Clinical Research ,Health Services ,Health and social care services research ,8.1 Organisation and delivery of services ,Good Health and Well Being ,Health Services Accessibility ,Humans ,Neurology ,Societies ,Medical ,Telemedicine ,United States ,Clinical Sciences ,Neurosciences ,Cognitive Sciences ,Neurology & Neurosurgery - Abstract
Telehealth services complement in-person neurologic care. The American Academy of Neurology supports patient access to telehealth services regardless of location, coverage for telehealth services by all subscriber benefits and insurance, equitable provider reimbursement, simplified state licensing requirements easing access to virtual care, and expanding telehealth research and quality initiatives. The roles and responsibilities of providers should be clearly delineated in telehealth service models.
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- 2021
61. Opioid-Free Analgesia Provides Pain Control Following Thumb Carpometacarpal Joint Arthroplasty
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Hysong, Alexander A., Odum, Susan M., Lake, Nicholas H., Hietpas, Kayla T., Michalek, Caleb J., Hamid, Nady, Gaston, Raymond G., Loeffler, Bryan J., Chapman, Todd M., Jr, Cohen, Bruce E., Connor, Patrick M., Curtin, Brian M., Davis, W. Hodges, Ellington, J. Kent, Fleischli, James E., Ford, Samuel E., Irwin, Todd A., Jones, Carroll P., III, Alden Milam, R., IV, Saltzman, Bryan M., Segebarth, P. Bradley P., Schiffern, Shadley C., and Shawen, Scott B.
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- 2023
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62. Giant nonlinear optical responses from photon avalanching nanoparticles
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Lee, Changhwan, Xu, Emma, Liu, Yawei, Teitelboim, Ayelet, Yao, Kaiyuan, Fernandez-Bravo, Angel, Kotulska, Agata, Nam, Sang Hwan, Suh, Yung Doug, Bednarkiewicz, Artur, Cohen, Bruce E., Chan, Emory M., and Schuck, P. James
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Physics - Optics ,Condensed Matter - Mesoscale and Nanoscale Physics ,Condensed Matter - Materials Science ,Condensed Matter - Other Condensed Matter - Abstract
Avalanche phenomena leverage steeply nonlinear dynamics to generate disproportionately high responses from small perturbations and are found in a multitude of events and materials, enabling technologies including optical phase-conjugate imaging, infrared quantum counting, and efficient upconverted lasing. However, the photon avalanching (PA) mechanism underlying these optical innovations has been observed only in bulk materials and aggregates, and typically at cryogenic temperatures, limiting its utility and impact. Here, we report the realization of PA at room temperature in single nanostructures--small, Tm-doped upconverting nanocrystals--and demonstrate their use in superresolution imaging at near-infrared (NIR) wavelengths within spectral windows of maximal biological transparency. Avalanching nanoparticles (ANPs) can be pumped by continuous-wave or pulsed lasers and exhibit all of the defining features of PA. These hallmarks include excitation power thresholds, long rise time at threshold, and a dominant excited-state absorption that is >13,000x larger than ground-state absorption. Beyond the avalanching threshold, ANP emission scales nonlinearly with the 26th power of pump intensity. This enables the realization of photon-avalanche single-beam superresolution imaging (PASSI), achieving sub-70 nm spatial resolution using only simple scanning confocal microscopy and before any computational analysis. Pairing their steep nonlinearity with existing superresolution techniques and computational methods, ANPs allow for imaging with higher resolution and at ca. 100-fold lower excitation intensities than is possible with other probes. The low PA threshold and exceptional photostability of ANPs also suggest their utility in a diverse array of applications including sub-wavelength bioimaging, IR detection, temperature and pressure transduction, neuromorphic computing, and quantum optics., Comment: 14 pages, 4 figures
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- 2020
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63. Controlled and Stable Patterning of Diverse Inorganic Nanocrystals on Crystalline Two-Dimensional Protein Arrays
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Mann, Victor R, Manea, Francesca, Borys, Nicholas J, Ajo-Franklin, Caroline M, and Cohen, Bruce E
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Medical Biotechnology ,Macromolecular and Materials Chemistry ,Biomedical and Clinical Sciences ,Chemical Sciences ,Nanotechnology ,Bioengineering ,Bacterial Proteins ,Gold ,Metal Nanoparticles ,Models ,Molecular ,Nanoparticles ,Optical Imaging ,Protein Conformation ,beta-Strand ,Quantum Dots ,Medicinal and Biomolecular Chemistry ,Biochemistry and Cell Biology ,Medical Biochemistry and Metabolomics ,Biochemistry & Molecular Biology ,Biochemistry and cell biology ,Medical biochemistry and metabolomics ,Medicinal and biomolecular chemistry - Abstract
Controlled patterning of nanoparticles on bioassemblies enables synthesis of complex materials for applications in optics, nanoelectronics, and sensing. Biomolecular self-assembly offers molecular control for engineering patterned nanomaterials, but current approaches have been limited in their ability to combine high nanoparticle coverage with generality that enables incorporation of multiple nanoparticle types. Here, we synthesize photonic materials on crystalline two-dimensional (2D) protein sheets using orthogonal bioconjugation reactions, organizing quantum dots (QDs), gold nanoparticles (AuNPs), and upconverting nanoparticles along the surface-layer (S-layer) protein SbsB from the extremophile Geobacillus stearothermophilus. We use electron and optical microscopy to show that isopeptide bond-forming SpyCatcher and SnoopCatcher systems enable the simultaneous and controlled conjugation of multiple types of nanoparticles (NPs) at high densities along the SbsB sheets. These NP conjugation reactions are orthogonal to each other and to Au-thiol bond formation, allowing tailorable nanoparticle combinations at sufficient labeling efficiencies to permit optical interactions between nanoparticles. Fluorescence lifetime imaging of SbsB sheets conjugated to QDs and AuNPs at distinct attachment sites shows spatially heterogeneous QD emission, with shorter radiative decays and brighter fluorescence arising from plasmonic enhancement at short interparticle distances. This specific, stable, and efficient conjugation of NPs to 2D protein sheets enables the exploration of interactions between pairs of nanoparticles at defined distances for the engineering of protein-based photonic nanomaterials.
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- 2021
64. X‑ray-Based Techniques to Study the Nano–Bio Interface
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Sanchez-Cano, Carlos, Alvarez-Puebla, Ramon A, Abendroth, John M, Beck, Tobias, Blick, Robert, Cao, Yuan, Caruso, Frank, Chakraborty, Indranath, Chapman, Henry N, Chen, Chunying, Cohen, Bruce E, Conceição, Andre LC, Cormode, David P, Cui, Daxiang, Dawson, Kenneth A, Falkenberg, Gerald, Fan, Chunhai, Feliu, Neus, Gao, Mingyuan, Gargioni, Elisabetta, Glüer, Claus-C, Grüner, Florian, Hassan, Moustapha, Hu, Yong, Huang, Yalan, Huber, Samuel, Huse, Nils, Kang, Yanan, Khademhosseini, Ali, Keller, Thomas F, Körnig, Christian, Kotov, Nicholas A, Koziej, Dorota, Liang, Xing-Jie, Liu, Beibei, Liu, Sijin, Liu, Yang, Liu, Ziyao, Liz-Marzán, Luis M, Ma, Xiaowei, Machicote, Andres, Maison, Wolfgang, Mancuso, Adrian P, Megahed, Saad, Nickel, Bert, Otto, Ferdinand, Palencia, Cristina, Pascarelli, Sakura, Pearson, Arwen, Peñate-Medina, Oula, Qi, Bing, Rädler, Joachim, Richardson, Joseph J, Rosenhahn, Axel, Rothkamm, Kai, Rübhausen, Michael, Sanyal, Milan K, Schaak, Raymond E, Schlemmer, Heinz-Peter, Schmidt, Marius, Schmutzler, Oliver, Schotten, Theo, Schulz, Florian, Sood, AK, Spiers, Kathryn M, Staufer, Theresa, Stemer, Dominik M, Stierle, Andreas, Sun, Xing, Tsakanova, Gohar, Weiss, Paul S, Weller, Horst, Westermeier, Fabian, Xu, Ming, Yan, Huijie, Zeng, Yuan, Zhao, Ying, Zhao, Yuliang, Zhu, Dingcheng, Zhu, Ying, and Parak, Wolfgang J
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Medical Biotechnology ,Biomedical and Clinical Sciences ,Physical Sciences ,Bioengineering ,Nanotechnology ,Generic health relevance ,Lasers ,Nanoparticles ,Radiography ,Synchrotrons ,X-Rays ,nano-bio interface ,X-ray techniques ,synchrotron radiation ,imaging ,nanoparticles ,delivery ,degradation ,spectroscopy ,nano−bio interface ,Nanoscience & Nanotechnology - Abstract
X-ray-based analytics are routinely applied in many fields, including physics, chemistry, materials science, and engineering. The full potential of such techniques in the life sciences and medicine, however, has not yet been fully exploited. We highlight current and upcoming advances in this direction. We describe different X-ray-based methodologies (including those performed at synchrotron light sources and X-ray free-electron lasers) and their potentials for application to investigate the nano-bio interface. The discussion is predominantly guided by asking how such methods could better help to understand and to improve nanoparticle-based drug delivery, though the concepts also apply to nano-bio interactions in general. We discuss current limitations and how they might be overcome, particularly for future use in vivo.
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- 2021
65. Theorising mental health: Introduction to special issue
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Cohen, Bruce MZ
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- 2023
66. Nitinol Staple Use in Primary Arthrodesis of Lisfranc Fracture-Dislocations
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Dombrowsky, Alexander R., primary, Strickland, Carson D., additional, Walsh, Devin F., additional, Hietpas, Kayla, additional, Conti, Matthew S., additional, Irwin, Todd A., additional, Cohen, Bruce E., additional, Ellington, J. Kent, additional, Jones, Carroll P., additional, Shawen, Scott B., additional, and Ford, Samuel E., additional
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- 2024
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67. Giant nonlinear optical responses from photon-avalanching nanoparticles
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Lee, Changhwan, Xu, Emma Z, Liu, Yawei, Teitelboim, Ayelet, Yao, Kaiyuan, Fernandez-Bravo, Angel, Kotulska, Agata M, Nam, Sang Hwan, Suh, Yung Doug, Bednarkiewicz, Artur, Cohen, Bruce E, Chan, Emory M, and Schuck, P James
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Quantum Physics ,Engineering ,Atomic ,Molecular and Optical Physics ,Physical Sciences ,Bioengineering ,Nanotechnology ,physics.optics ,cond-mat.mes-hall ,cond-mat.mtrl-sci ,cond-mat.other ,General Science & Technology - Abstract
Avalanche phenomena use steeply nonlinear dynamics to generate disproportionately large responses from small perturbations, and are found in a multitude of events and materials1. Photon avalanching enables technologies such as optical phase-conjugate imaging2, infrared quantum counting3 and efficient upconverted lasing4-6. However, the photon-avalanching mechanism underlying these optical applications has been observed only in bulk materials and aggregates6,7, limiting its utility and impact. Here we report the realization of photon avalanching at room temperature in single nanostructures-small, Tm3+-doped upconverting nanocrystals-and demonstrate their use in super-resolution imaging in near-infrared spectral windows of maximal biological transparency. Avalanching nanoparticles (ANPs) can be pumped by continuous-wave lasers, and exhibit all of the defining features of photon avalanching, including clear excitation-power thresholds, exceptionally long rise time at threshold, and a dominant excited-state absorption that is more than 10,000 times larger than ground-state absorption. Beyond the avalanching threshold, ANP emission scales nonlinearly with the 26th power of the pump intensity, owing to induced positive optical feedback in each nanocrystal. This enables the experimental realization of photon-avalanche single-beam super-resolution imaging7 with sub-70-nanometre spatial resolution, achieved by using only simple scanning confocal microscopy and without any computational analysis. Pairing their steep nonlinearity with existing super-resolution techniques and computational methods8-10, ANPs enable imaging with higher resolution and at excitation intensities about 100 times lower than other probes. The low photon-avalanching threshold and excellent photostability of ANPs also suggest their utility in a diverse array of applications, including sub-wavelength imaging7,11,12 and optical and environmental sensing13-15.
- Published
- 2021
68. Midterm Outcomes of the INBONETM II Total Ankle Arthroplasty
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Loewy, Evan, Conti, Matthew S., Jones, Carroll P., Cohen, Bruce E., Anderson, Robert B., Irwin, Todd A., and Davis, W. Hodges
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- 2023
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69. Currently available means to achieve personalized psychiatry
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Cohen, Bruce M. and Harris, Peter Q.
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- 2023
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70. Monopoly Control
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Abbott, Malcolm, primary and Cohen, Bruce, additional
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- 2023
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71. Distinguishing Potassium Channel Resting State Conformations in Live Cells with Environment-Sensitive Fluorescence
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Fletcher-Taylor, Sebastian, Thapa, Parashar, Sepela, Rebecka J, Kaakati, Rayan, Yarov-Yarovoy, Vladimir, Sack, Jon T, and Cohen, Bruce E
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Analytical Chemistry ,Biochemistry and Cell Biology ,Biological Sciences ,Medicinal and Biomolecular Chemistry ,Chemical Sciences ,Bioengineering ,Neurosciences ,Underpinning research ,1.1 Normal biological development and functioning ,Generic health relevance ,Fluorescence ,Ion Channel Gating ,Membrane Potentials ,Potassium Channels ,Spider Venoms ,Potassium channel ,fluorophore ,toxin ,allostery ,structure ,spectroscopy ,Biochemistry and cell biology ,Analytical chemistry ,Medicinal and biomolecular chemistry - Abstract
Ion channels are polymorphic membrane proteins whose high-resolution structures offer images of individual conformations, giving us starting points for identifying the complex and transient allosteric changes that give rise to channel physiology. Here, we report live-cell imaging of voltage-dependent structural changes of voltage-gated Kv2.1 channels using peptidyl tarantula toxins labeled with an environment-sensitive fluorophore, whose spectral shifts enable identification of voltage-dependent conformation changes in the resting voltage sensing domain (VSD) of the channel. We synthesize a new environment-sensitive, far-red fluorophore, julolidine phenoxazone (JP) azide, and conjugate it to tarantula toxin GxTX to characterize Kv2.1 VSD allostery during membrane depolarization. JP has an inherent response to the polarity of its immediate surroundings, offering site-specific structural insight into each channel conformation. Using voltage-clamp spectroscopy to collect emission spectra as a function of membrane potential, we find that they vary with toxin labeling site, the presence of Kv2 channels, and changes in membrane potential. With a high-affinity conjugate in which the fluorophore itself interacts closely with the channel, the emission shift midpoint is 50 mV more negative than the Kv2.1 gating current midpoint. This suggests that substantial conformational changes at the toxin-channel interface are associated with early gating charge transitions and these are not concerted with VSD motions at more depolarized potentials. These fluorescent probes enable study of conformational changes that can be correlated with electrophysiology, putting channel structures and models into a context of live-cell membranes and physiological states.
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- 2020
72. Theoretical Plasma Physics
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Kaufman, Allan N. and Cohen, Bruce I.
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Physics - Plasma Physics - Abstract
These lecture notes were presented by Allan N. Kaufman in his graduate plasma theory course and a follow-on special topics course (Physics 242A, B, C and Physics 250 at the University of California Berkeley). The notes follow the order of the lectures. The equations and derivations are as Kaufman presented, but the text is a reconstruction of Kaufman's discussion and commentary. The notes were transcribed by Bruce I. Cohen in 1971 and 1972, and word-processed, edited, and illustrations added by Cohen in 2017 and 2018. The series of lectures are divided into four major parts: (1) collisionless Vlasov plasmas (linear theory of waves and instabilities with and without an applied magnetic field, Vlasov-Poisson and Vlasov-Maxwell systems, WKBJ eikonal theory of wave propagation); (2) nonlinear Vlasov plasmas and miscellaneous topics (the plasma dispersion function, singular solutions of the Vlasov-Poisson system, pulse-response solutions for initial-value problems, Gardiner's stability theorem, gyroresonant effects, nonlinear waves, particle trapping in waves, quasi-linear theory, nonlinear three-wave interactions); (3) plasma collisional and discreteness phenomena (test-particle theory of dynamic friction and wave emission, classical resistivity, extension of test-particle theory to many-particle phenomena and the derivation of the Boltzmann and Lenard-Balescu equations, the Fokker-Planck collision operator, a general scattering theory, nonlinear Landau damping, radiation transport, and Dupree's theory of clumps); (4) nonuniform plasmas (adiabatic invariance, guiding center drifts, hydromagnetic theory, introduction to drift-wave stability theory)., Comment: 264 pages, 38 numbered figures, 1 table, 2 photographs
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- 2019
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73. A single TRPV1 amino acid controls species sensitivity to capsaicin.
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Chu, Ying, Cohen, Bruce E, and Chuang, Huai-Hu
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Animals ,Chickens ,Humans ,Rats ,Capsaicin ,Amino Acids ,Amino Acid Substitution ,Species Specificity ,Structure-Activity Relationship ,Drug Resistance ,Mutation ,TRPV Cation Channels - Abstract
Chili peppers produce capsaicin (a vanilloid) that activates the transient receptor potential cation channel subfamily V member 1 (TRPV1) on sensory neurons to alter their membrane potential and induce pain. To identify residues responsible for differential TRPV1 capsaicin sensitivity among species, we used intracellular Ca2+ imaging to characterize chimeras composed of capsaicin-sensitive rat TRPV1 (rTRPV1) and capsaicin-insensitive chicken TRPV1 (cTRPV1) exposed to a series of capsaicinoids. We found that chimeras containing rat E570-V686 swapped into chicken receptors displayed capsaicin sensitivity, and that simply changing the alanine at position 578 in the S4-S5 helix of the chicken receptor to a glutamic acid was sufficient to endow it with capsaicin sensitivity in the micromolar range. Moreover, introduction of lysine, glutamine or proline at residue A578 also elicited capsaicin sensitivity in cTRPV1. Similarly, replacing corresponding rTRPV1 residue E570 with lysine or glutamine retained capsaicin sensitivity. The hydrophilic capsaicin analog Cap-EA activated a cTRPV1-A578E mutant, suggesting that A578 may participate in vanilloid binding. The hydrophilic vanilloid agonist zingerone did not activate any A578 mutants with capsaicin sensitivity, suggesting that the vanilloid group alone is not sufficient for receptor activation. Our study demonstrates that a subtle modification of TRPV1 in different species globally alters capsaicin responses.
- Published
- 2020
74. Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson’s Disease
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Schweitzer, Jeffrey S, Song, Bin, Herrington, Todd M, Park, Tae-Yoon, Lee, Nayeon, Ko, Sanghyeok, Jeon, Jeha, Cha, Young, Kim, Kyungsang, Li, Quanzheng, Henchcliffe, Claire, Kaplitt, Michael, Neff, Carolyn, Rapalino, Otto, Seo, Hyemyung, Lee, In-Hee, Kim, Jisun, Kim, Taewoo, Petsko, Gregory A, Ritz, Jerome, Cohen, Bruce M, Kong, Sek-Won, Leblanc, Pierre, Carter, Bob S, and Kim, Kwang-Soo
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Medical Biotechnology ,Biomedical and Clinical Sciences ,Neurodegenerative ,Transplantation ,Regenerative Medicine ,Stem Cell Research - Induced Pluripotent Stem Cell ,Clinical Research ,Stem Cell Research - Induced Pluripotent Stem Cell - Human ,Stem Cell Research ,Parkinson's Disease ,Brain Disorders ,Neurosciences ,Neurological ,Good Health and Well Being ,Aged ,Animals ,Basal Ganglia ,Cell Differentiation ,Disease Models ,Animal ,Dopaminergic Neurons ,Follow-Up Studies ,Humans ,Induced Pluripotent Stem Cells ,Male ,Mice ,Mice ,SCID ,Parkinson Disease ,Pars Compacta ,Positron-Emission Tomography ,Putamen ,Tomography ,X-Ray Computed ,Transplantation ,Autologous ,Transplantation ,Homologous ,Medical and Health Sciences ,General & Internal Medicine ,Biomedical and clinical sciences ,Health sciences - Abstract
We report the implantation of patient-derived midbrain dopaminergic progenitor cells, differentiated in vitro from autologous induced pluripotent stem cells (iPSCs), in a patient with idiopathic Parkinson's disease. The patient-specific progenitor cells were produced under Good Manufacturing Practice conditions and characterized as having the phenotypic properties of substantia nigra pars compacta neurons; testing in a humanized mouse model (involving peripheral-blood mononuclear cells) indicated an absence of immunogenicity to these cells. The cells were implanted into the putamen (left hemisphere followed by right hemisphere, 6 months apart) of a patient with Parkinson's disease, without the need for immunosuppression. Positron-emission tomography with the use of fluorine-18-L-dihydroxyphenylalanine suggested graft survival. Clinical measures of symptoms of Parkinson's disease after surgery stabilized or improved at 18 to 24 months after implantation. (Funded by the National Institutes of Health and others.).
- Published
- 2020
75. Controlled Assembly of Upconverting Nanoparticles for Low-Threshold Microlasers and Their Imaging in Scattering Media
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Liu, Yawei, Teitelboim, Ayelet, Fernandez-Bravo, Angel, Yao, Kaiyuan, Altoe, M Virginia P, Aloni, Shaul, Zhang, Chunhua, Cohen, Bruce E, Schuck, P James, and Chan, Emory M
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Physical Sciences ,Engineering ,Nanotechnology ,Bioengineering ,Generic health relevance ,Lasers ,Microspheres ,Nanoparticles ,Particle Size ,Surface Properties ,Titanium ,anti-Stokes laser ,self-assembly ,nanoparticle ,microlaser ,upconversion ,Nanoscience & Nanotechnology - Abstract
Micron-sized lasers fabricated from upconverting nanoparticles (UCNP) coupled to whispering gallery mode (WGM) microresonators can exhibit continuous-wave anti-Stokes lasing useful for tracking cells, environmental sensing, and coherent stimulation of biological activity. The integration of these microlasers into organisms and microelectronics requires even smaller diameters, however, which raises threshold pump powers beyond practical limits for biological applications. To meet the need for low lasing thresholds and high fidelity fabrication methods, we use correlative optical and electron microscopy to uncover the nanoparticle assembly process and structural factors that determine efficient upconverted lasing. We show that 5 μm microspheres with controlled submonolayer UCNP coatings exhibit, on average, 25-fold lower laser thresholds (1.7 ± 0.7 kW/cm2) compared to the mean values of the lowest threshold UCNP lasers, and variability is reduced 30-fold. WGMs are observed in the upconversion spectra for TiO2-coated microspheres as small as 3 μm, a size at which optical losses had previously prevented such observations. Finally, we demonstrate that the WGM signatures of these upconverting microlasers can be imaged and distinguished through tissue-mimicking phantoms. These advances will enable the fabrication of more efficient upconverting lasers for imaging, sensing, and actuation in optically complex environments.
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- 2020
76. Ligand-conjugated quantum dots for fast sub-diffraction protein tracking in acute brain slices
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Thal, Lucas B, Mann, Victor R, Sprinzen, David, McBride, James R, Reid, Kemar R, Tomlinson, Ian D, McMahon, Douglas G, Cohen, Bruce E, and Rosenthal, Sandra J
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Engineering ,Nanotechnology ,Neurosciences ,Bioengineering ,Biotechnology ,1.1 Normal biological development and functioning ,Underpinning research ,Animals ,Brain ,Brain Chemistry ,Ligands ,Mice ,Microscopy ,Fluorescence ,Microtomy ,Proteins ,Quantum Dots ,Selenium Compounds ,Staining and Labeling ,Zinc Compounds ,Medicinal and Biomolecular Chemistry ,Biochemistry and Cell Biology ,Medical Biotechnology ,Medical biotechnology ,Biomedical engineering - Abstract
Semiconductor quantum dots (QDs) have demonstrated utility in long-term single particle tracking of membrane proteins in live cells in culture. To extend the superior optical properties of QDs to more physiologically relevant cell platforms, such as acute brain slices, we examine the photophysics of compact ligand-conjugated CdSe/CdS QDs using both ensemble and single particle analysis in brain tissue media. We find that symmetric core passivation is critical for both photostability in oxygenated media and for prolonged single particle imaging in brain slices. We then demonstrate the utility of these QDs by imaging single dopamine transporters in acute brain slices, achieving 20 nm localization precision at 10 Hz frame rates. These findings detail design requirements needed for new QD probes in complex living environments, and open the door to physiologically relevant studies that capture the utility of QD probes in acute brain slices.
- Published
- 2020
77. Psychiatric Expansion and the Rise of Workplace Mental Health Initiatives
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Cohen, Bruce M. Z. and Harbusch, Martin, editor
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- 2022
- Full Text
- View/download PDF
78. Ultralow-threshold, continuous-wave upconverting lasing from subwavelength plasmons
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Fernandez-Bravo, Angel, Wang, Danqing, Barnard, Edward S, Teitelboim, Ayelet, Tajon, Cheryl, Guan, Jun, Schatz, George C, Cohen, Bruce E, Chan, Emory M, Schuck, P James, and Odom, Teri W
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Physical Sciences ,Quantum Physics ,Engineering ,Nanotechnology ,Lasers ,Optical Phenomena ,Photons ,Temperature ,Nanoscience & Nanotechnology - Abstract
Miniaturized lasers are an emerging platform for generating coherent light for quantum photonics, in vivo cellular imaging, solid-state lighting and fast three-dimensional sensing in smartphones1-3. Continuous-wave lasing at room temperature is critical for integration with opto-electronic devices and optimal modulation of optical interactions4,5. Plasmonic nanocavities integrated with gain can generate coherent light at subwavelength scales6-9, beyond the diffraction limit that constrains mode volumes in dielectric cavities such as semiconducting nanowires10,11. However, insufficient gain with respect to losses and thermal instabilities in nanocavities has limited all nanoscale lasers to pulsed pump sources and/or low-temperature operation6-9,12-15. Here, we show continuous-wave upconverting lasing at room temperature with record-low thresholds and high photostability from subwavelength plasmons. We achieve selective, single-mode lasing from Yb3+/Er3+-co-doped upconverting nanoparticles conformally coated on Ag nanopillar arrays that support a single, sharp lattice plasmon cavity mode and greater than wavelength λ/20 field confinement in the vertical dimension. The intense electromagnetic near-fields localized in the vicinity of the nanopillars result in a threshold of 70 W cm-2, orders of magnitude lower than other small lasers. Our plasmon-nanoarray upconverting lasers provide directional, ultra-stable output at visible frequencies under near-infrared pumping, even after six hours of constant operation, which offers prospects in previously unrealizable applications of coherent nanoscale light.
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- 2019
79. Clinical phenotypes of five patients with psychotic disorders carrying rare schizophrenia-associated loss-of-function variants
- Author
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Cohen, Bruce M., Singh, Tarjinder, Öngür, Dost, Konstantin, Grace E., and Gardner, Margaret E.
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- 2022
- Full Text
- View/download PDF
80. Diagnostic terms psychiatrists prefer to use for common psychotic and personality disorders
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Cohen, Bruce M., Öngür, Dost, Babb, Suzann M., and Harris, Peter Q.
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- 2022
- Full Text
- View/download PDF
81. Correspondence of fentanyl brain pharmacokinetics and behavior measured via engineering opioids biosensors and computational ethology
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Muthusamy, Anand K, primary, Rosenberg, Matthew, additional, Kim, Charlene H, additional, Wang, Alexander Z, additional, Ebisu, Haruka, additional, Chin, Theodore M, additional, Koranne, Ashil, additional, Marvin, Jonathan S, additional, Cohen, Bruce N, additional, Looger, Loren L, additional, Oka, Yuki, additional, Meister, Markus, additional, and Lester, Henry A, additional
- Published
- 2024
- Full Text
- View/download PDF
82. Sphingosine 1‐phosphate receptor modulators in multiple sclerosis treatment: A practical review
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Coyle, Patricia K., primary, Freedman, Mark S., additional, Cohen, Bruce A., additional, Cree, Bruce A. C., additional, and Markowitz, Clyde E., additional
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- 2024
- Full Text
- View/download PDF
83. Characterization of Fatigue in Primary Mitochondrial Myopathies
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Karaa, Amel, primary, Johnson, Nathan, additional, Clarkson, Ian, additional, Newman, Wendy, additional, Dorenbaum, Alejandro, additional, and Cohen, Bruce H., additional
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- 2024
- Full Text
- View/download PDF
84. The 22q11.2 region regulates presynaptic gene-products linked to schizophrenia
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Nehme, Ralda, Pietiläinen, Olli, Artomov, Mykyta, Tegtmeyer, Matthew, Valakh, Vera, Lehtonen, Leevi, Bell, Christina, Singh, Tarjinder, Trehan, Aditi, Sherwood, John, Manning, Danielle, Peirent, Emily, Malik, Rhea, Guss, Ellen J., Hawes, Derek, Beccard, Amanda, Bara, Anne M., Hazelbaker, Dane Z., Zuccaro, Emanuela, Genovese, Giulio, Loboda, Alexander A., Neumann, Anna, Lilliehook, Christina, Kuismin, Outi, Hamalainen, Eija, Kurki, Mitja, Hultman, Christina M., Kähler, Anna K., Paulo, Joao A., Ganna, Andrea, Madison, Jon, Cohen, Bruce, McPhie, Donna, Adolfsson, Rolf, Perlis, Roy, Dolmetsch, Ricardo, Farhi, Samouil, McCarroll, Steven, Hyman, Steven, Neale, Ben, Barrett, Lindy E., Harper, Wade, Palotie, Aarno, Daly, Mark, and Eggan, Kevin
- Published
- 2022
- Full Text
- View/download PDF
85. Bright sub-20 nm cathodoluminescent nanoprobes for multicolor electron microscopy
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Prigozhin, Maxim B., Maurer, Peter C., Courtis, Alexandra M., Liu, Nian, Wisser, Michael D., Siefe, Chris, Tian, Bining, Chan, Emory, Song, Guosheng, Fischer, Stefan, Aloni, Shaul, Ogletree, D. Frank, Barnard, Edward S., Joubert, Lydia-Marie, Rao, Jianghong, Alivisatos, A. Paul, Macfarlane, Roger M., Cohen, Bruce E., Cui, Yi, Dionne, Jennifer A., and Chu, Steven
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Condensed Matter - Materials Science ,Physics - Biological Physics ,Physics - Optics - Abstract
Electron microscopy (EM) has been instrumental in our understanding of biological systems ranging from subcellular structures to complex organisms. Although EM reveals cellular morphology with nanoscale resolution, it does not provide information on the location of proteins within a cellular context. An EM-based bioimaging technology capable of localizing individual proteins and resolving protein-protein interactions with respect to cellular ultrastructure would provide important insights into the molecular biology of a cell. Here, we report on the development of luminescent nanoprobes potentially suitable for labeling biomolecules in a multicolor EM modality. In this approach, the labels are based on lanthanide-doped nanoparticles that emit light under electron excitation in a process known as cathodoluminescence (CL). Our results suggest that the optimization of nanoparticle composition, synthesis protocols and electron imaging conditions could enable high signal-to-noise localization of biomolecules with a sub-20-nm resolution, limited only by the nanoparticle size. In ensemble measurements, these luminescent labels exhibit narrow spectra of nine distinct colors that are characteristic of the corresponding rare-earth dopant type.
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- 2018
- Full Text
- View/download PDF
86. Economics, ideology, and the creation and performance of state-owned electricity utilities in Australia, 1900 to 1950
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Abbott, Malcolm and Cohen, Bruce
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- 2022
- Full Text
- View/download PDF
87. Bright sub-20-nm cathodoluminescent nanoprobes for electron microscopy
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Prigozhin, Maxim B, Maurer, Peter C, Courtis, Alexandra M, Liu, Nian, Wisser, Michael D, Siefe, Chris, Tian, Bining, Chan, Emory, Song, Guosheng, Fischer, Stefan, Aloni, Shaul, Ogletree, D Frank, Barnard, Edward S, Joubert, Lydia-Marie, Rao, Jianghong, Alivisatos, A Paul, Macfarlane, Roger M, Cohen, Bruce E, Cui, Yi, Dionne, Jennifer A, and Chu, Steven
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Biological Sciences ,Engineering ,Nanotechnology ,Bioengineering ,Generic health relevance ,Fluorescent Dyes ,Microscopy ,Electron ,Transmission ,Nanoparticles ,cond-mat.mtrl-sci ,physics.bio-ph ,physics.optics ,Nanoscience & Nanotechnology - Abstract
Electron microscopy has been instrumental in our understanding of complex biological systems. Although electron microscopy reveals cellular morphology with nanoscale resolution, it does not provide information on the location of different types of proteins. An electron-microscopy-based bioimaging technology capable of localizing individual proteins and resolving protein-protein interactions with respect to cellular ultrastructure would provide important insights into the molecular biology of a cell. Here, we synthesize small lanthanide-doped nanoparticles and measure the absolute photon emission rate of individual nanoparticles resulting from a given electron excitation flux (cathodoluminescence). Our results suggest that the optimization of nanoparticle composition, synthesis protocols and electron imaging conditions can lead to sub-20-nm nanolabels that would enable high signal-to-noise localization of individual biomolecules within a cellular context. In ensemble measurements, these labels exhibit narrow spectra of nine distinct colours, so the imaging of biomolecules in a multicolour electron microscopy modality may be possible.
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- 2019
88. Determining the pharmacokinetics of nicotinic drugs in the endoplasmic reticulum using biosensors
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Shivange, Amol V, Borden, Philip M, Muthusamy, Anand K, NIchols, Aaron, Bera, Kallol, Bao, Huan, Bishara, Ishak, Jeon, Janice, Mulcahy, Matthew J, Cohen, Bruce, O'Riordan, Saidhbhe L, Kim, Charlene, Dougherty, Dennis A, Chapman, Edwin R, Marvin, Jonathan, Looger, Loren, and Lester, Henry A
- Published
- 2019
89. Dysregulated protocadherin-pathway activity as an intrinsic defect in induced pluripotent stem cell–derived cortical interneurons from subjects with schizophrenia
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Shao, Zhicheng, Noh, Haneul, Bin Kim, Woong, Ni, Peiyan, Nguyen, Christine, Cote, Sarah E, Noyes, Elizabeth, Zhao, Joyce, Parsons, Teagan, Park, James M, Zheng, Kelvin, Park, Joshua J, Coyle, Joseph T, Weinberger, Daniel R, Straub, Richard E, Berman, Karen F, Apud, Jose, Ongur, Dost, Cohen, Bruce M, McPhie, Donna L, Rapoport, Judith L, Perlis, Roy H, Lanz, Thomas A, Xi, Hualin Simon, Yin, Changhong, Huang, Weihua, Hirayama, Teruyoshi, Fukuda, Emi, Yagi, Takeshi, Ghosh, Sulagna, Eggan, Kevin C, Kim, Hae-Young, Eisenberg, Leonard M, Moghadam, Alexander A, Stanton, Patric K, Cho, Jun-Hyeong, and Chung, Sangmi
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Biomedical and Clinical Sciences ,Biological Psychology ,Neurosciences ,Psychology ,Pharmacology and Pharmaceutical Sciences ,Stem Cell Research ,Brain Disorders ,Regenerative Medicine ,Mental Health ,Schizophrenia ,2.1 Biological and endogenous factors ,Aetiology ,Mental health ,Neurological ,Animals ,Cadherins ,Female ,Humans ,Induced Pluripotent Stem Cells ,Interneurons ,Male ,Mice ,Mice ,Knockout ,Prefrontal Cortex ,Protocadherins ,Signal Transduction ,Synapses ,Cognitive Sciences ,Neurology & Neurosurgery ,Biological psychology - Abstract
We generated cortical interneurons (cINs) from induced pluripotent stem cells derived from 14 healthy controls and 14 subjects with schizophrenia. Both healthy control cINs and schizophrenia cINs were authentic, fired spontaneously, received functional excitatory inputs from host neurons, and induced GABA-mediated inhibition in host neurons in vivo. However, schizophrenia cINs had dysregulated expression of protocadherin genes, which lie within documented schizophrenia loci. Mice lacking protocadherin-α showed defective arborization and synaptic density of prefrontal cortex cINs and behavioral abnormalities. Schizophrenia cINs similarly showed defects in synaptic density and arborization that were reversed by inhibitors of protein kinase C, a downstream kinase in the protocadherin pathway. These findings reveal an intrinsic abnormality in schizophrenia cINs in the absence of any circuit-driven pathology. They also demonstrate the utility of homogenous and functional populations of a relevant neuronal subtype for probing pathogenesis mechanisms during development.
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- 2019
90. Energy Transfer Networks within Upconverting Nanoparticles Are Complex Systems with Collective, Robust, and History-Dependent Dynamics
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Teitelboim, Ayelet, Tian, Bining, Garfield, David J, Fernandez-Bravo, Angel, Gotlin, Adam C, Schuck, P James, Cohen, Bruce E, and Chan, Emory M
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Bioengineering ,Affordable and Clean Energy ,Chemical Sciences ,Engineering ,Technology ,Physical Chemistry - Abstract
Applications of photon upconverting nanoparticles (UCNPs) in biological imaging and solar energy conversion demand that their anti-Stokes luminescence be both tunable and efficient. Rational design of more efficient UCNPs requires an understanding of energy transfer (ET) between their lanthanide dopants, dynamics that are typically characterized by measuring luminescence lifetimes. Existing knowledge, however, cannot explain basic observations in lifetime experiments, such as their dependence on excitation power, significantly limiting the generality and reliability of lifetime measurements. Here, we elucidate the origins of the ET dynamics and luminescence lifetimes of Yb3+-, Er3+-co-doped NaYF4 UCNPs using time-resolved luminescence and novel applications of rate equations and stochastic simulations. Experiments and calculations consistently show that at high concentrations of Er3+, the luminescence lifetimes of UCNPs decrease as much as six-fold when excitation power densities are increased over 6 orders of magnitude. Since power-dependent lifetimes cannot be explained by intrinsic relaxation rates of individual transitions, we analyze lifetime data by treating each UCNP as a complex ET network. We find that UCNP ET networks exhibit four distinguishing characteristics of complex systems: collectivity, nonlinear feedback, robustness, and history dependence. We conclude that power-dependent lifetimes are the consequence of thousands of minor relaxation pathways that act collectively to depopulate and repopulate Er3+ emitting levels. These ET pathways are dependent on past excitation power because they originate from excited donors and excited acceptors; however, each transition has an unexpectedly small impact on lifetimes due to negative feedback in the network. This robustness is determined by systematically "knocking out", or disabling, ET transitions in kinetic models. Our classification of UCNP ET networks as complex systems explains why UCNP luminescence lifetimes do not match the intrinsic lifetimes of emitting states. In the future, UCNP networks may be engineered to rival the complexity of biological networks that pattern features with unmatched precision. ©
- Published
- 2019
91. Engineering the S‑Layer of Caulobacter crescentus as a Foundation for Stable, High-Density, 2D Living Materials
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Charrier, Marimikel, Li, Dong, Mann, Victor R, Yun, Lisa, Jani, Sneha, Rad, Behzad, Cohen, Bruce E, Ashby, Paul D, Ryan, Kathleen R, and Ajo-Franklin, Caroline M
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Biochemistry and Cell Biology ,Bioinformatics and Computational Biology ,Biological Sciences ,Regenerative Medicine ,Bioengineering ,1.3 Chemical and physical sciences ,Underpinning research ,Caulobacter crescentus ,Cell Membrane ,Cyanobacteria ,DNA ,Bacterial ,Gene Editing ,RsaA ,engineered living materials ,quantum dots ,Caulobacter ,biomaterial ,Medicinal and Biomolecular Chemistry ,Biomedical Engineering ,Biochemistry and cell biology ,Bioinformatics and computational biology - Abstract
Materials synthesized by organisms, such as bones and wood, combine the ability to self-repair with remarkable mechanical properties. This multifunctionality arises from the presence of living cells within the material and hierarchical assembly of different components across nanometer to micron scales. While creating engineered analogues of these natural materials is of growing interest, our ability to hierarchically order materials using living cells largely relies on engineered 1D protein filaments. Here, we lay the foundation for bottom-up assembly of engineered living material composites in 2D along the cell body using a synthetic biology approach. We engineer the paracrystalline surface-layer (S-layer) of Caulobacter crescentus to display SpyTag peptides that form irreversible isopeptide bonds to SpyCatcher-modified proteins, nanocrystals, and biopolymers on the extracellular surface. Using flow cytometry and confocal microscopy, we show that attachment of these materials to the cell surface is uniform, specific, and covalent, and its density can be controlled on the basis of the insertion location within the S-layer protein, RsaA. Moreover, we leverage the irreversible nature of this attachment to demonstrate via SDS-PAGE that the engineered S-layer can display a high density of materials, reaching 1 attachment site per 288 nm2. Finally, we show that ligation of quantum dots to the cell surface does not impair cell viability, and this composite material remains intact over a period of 2 weeks. Taken together, this work provides a platform for self-organization of soft and hard nanomaterials on a cell surface with precise control over 2D density, composition, and stability of the resulting composite, and is a key step toward building hierarchically ordered engineered living materials with emergent properties.
- Published
- 2019
92. A 25 micron-thin microscope for imaging upconverting nanoparticles with NIR-I and NIR-II illumination
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Najafiaghdam, Hossein, Papageorgiou, Efthymios, Torquato, Nicole A, Tian, Bining, Cohen, Bruce E, and Anwar, Mekhail
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Nanotechnology ,Biomedical Imaging ,Bioengineering ,Animals ,Lanthanoid Series Elements ,Male ,Mice ,Microscopy ,Fluorescence ,Miniaturization ,Nanoparticles ,intraoperative imaging ,upconverting nanoparticle ,time-resolved imaging ,NIR excitation ,Oncology and carcinogenesis - Abstract
Rationale: Intraoperative visualization in small surgical cavities and hard-to-access areas are essential requirements for modern, minimally invasive surgeries and demand significant miniaturization. However, current optical imagers require multiple hard-to-miniaturize components including lenses, filters and optical fibers. These components restrict both the form-factor and maneuverability of these imagers, and imagers largely remain stand-alone devices with centimeter-scale dimensions. Methods: We have engineered INSITE (Immunotargeted Nanoparticle Single-Chip Imaging Technology), which integrates the unique optical properties of lanthanide-based alloyed upconverting nanoparticles (aUCNPs) with the time-resolved imaging of a 25-micron thin CMOS-based (complementary metal oxide semiconductor) imager. We have synthesized core/shell aUCNPs of different compositions and imaged their visible emission with INSITE under either NIR-I and NIR-II photoexcitation. We characterized aUCNP imaging with INSITE across both varying aUCNP composition and 980 nm and 1550 nm excitation wavelengths. To demonstrate clinical experimental validity, we also conducted an intratumoral injection into LNCaP prostate tumors in a male nude mouse that was subsequently excised and imaged with INSITE. Results: Under the low illumination fluences compatible with live animal imaging, we measure aUCNP radiative lifetimes of 600 μs - 1.3 ms, which provides strong signal for time-resolved INSITE imaging. Core/shell NaEr0.6Yb0.4F4 aUCNPs show the highest INSITE signal when illuminated at either 980 nm or 1550 nm, with signal from NIR-I excitation about an order of magnitude brighter than from NIR-II excitation. The 55 μm spatial resolution achievable with this approach is demonstrated through imaging of aUCNPs in PDMS (polydimethylsiloxane) micro-wells, showing resolution of micrometer-scale targets with single-pixel precision. INSITE imaging of intratumoral NaEr0.8Yb0.2F4 aUCNPs shows a signal-to-background ratio of 9, limited only by photodiode dark current and electronic noise. Conclusion: This work demonstrates INSITE imaging of aUCNPs in tumors, achieving an imaging platform that is thinned to just a 25 μm-thin, planar form-factor, with both NIR-I and NIR-II excitation. Based on a highly paralleled array structure INSITE is scalable, enabling direct coupling with a wide array of surgical and robotic tools for seamless integration with tissue actuation, resection or ablation.
- Published
- 2019
93. Biosensors Show the Pharmacokinetics of S-Ketamine in the Endoplasmic Reticulum
- Author
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Bera, Kallol, Kamajaya, Aron, Shivange, Amol V, Muthusamy, Anand K, Nichols, Aaron L, Borden, Philip M, Grant, Stephen, Jeon, Janice, Lin, Elaine, Bishara, Ishak, Chin, Theodore M, Cohen, Bruce N, Kim, Charlene H, Unger, Elizabeth K, Tian, Lin, Marvin, Jonathan S, Looger, Loren L, and Lester, Henry A
- Subjects
Biochemistry and Cell Biology ,Biomedical and Clinical Sciences ,Biological Sciences ,Stem Cell Research ,Bioengineering ,Stem Cell Research - Induced Pluripotent Stem Cell - Human ,Neurosciences ,Stem Cell Research - Induced Pluripotent Stem Cell ,Generic health relevance ,antidepressants ,organelles ,green fluorescent protein ,protein engineering and design ,periplasmic binding proteins ,inside-out pharmacology ,iSketSnFR1 ,iSketSnFR2 ,Biochemistry and cell biology ,Biological psychology - Abstract
The target for the "rapid" (100-fold selectivity over other ligands tested, including R-ketamine. We targeted each of the sensors to either the plasma membrane (PM) or the endoplasmic reticulum (ER). Measurements on these biosensors expressed in Neuro2a cells and in human dopaminergic neurons differentiated from induced pluripotent stem cells (iPSCs) show that S-ketamine enters the ER within a few seconds after appearing in the external solution near the PM, then leaves as rapidly after S-ketamine is removed from the extracellular solution. In cells, S-slopes for the ER and PM-targeted sensors differ by
- Published
- 2019
94. Photostable and efficient upconverting nanocrystal-based chemical sensors
- Author
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Tajon, Cheryl A, Yang, Hao, Tian, Bining, Tian, Yue, Ercius, Peter, Schuck, P James, Chan, Emory M, and Cohen, Bruce E
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Atomic ,Molecular and Optical Physics ,Physical Sciences ,Condensed Matter Physics ,Nanotechnology ,Biotechnology ,Bioengineering ,Generic health relevance ,Affordable and Clean Energy ,Upconverting nanoparticles ,Sensors ,Fluorescence ,Energy transfer ,Photostability ,Optical Physics ,Materials Engineering ,Applied Physics ,Atomic ,molecular and optical physics ,Condensed matter physics - Abstract
Chemical sensing in living systems demands optical sensors that are bright, stable, and sensitive to the rapid dynamics of chemical signaling. Lanthanide-doped upconverting nanoparticles (UCNPs) efficiently convert near infrared (NIR) light to higher energy emission and allow biological systems to be imaged with no measurable background or photobleaching, and with reduced scatter for subsurface experiments. Despite their advantages as imaging probes, UCNPs have little innate chemical sensing ability and require pairing with organic fluorophores to act as biosensors, although the design of stable UCNP-fluorophore hybrids with efficient upconverted energy transfer (UET) has remained a challenge. Here, we report Yb3+- and Er3+-doped UCNP-fluorophore conjugates with UET efficiencies up to 88%, and photostabilities 100-fold greater by UET excitation than those of the free fluorophores under direct excitation. Despite adding distance between Er3+ donors and organic acceptors, thin inert shells significantly enhance overall emission without compromising UET efficiency. This can be explained by the large increase in quantum yield of Er3+ donors at the core/shell interface and the large number of fluorophore acceptors at the surface. Sensors excited by UET show increases in photostability well beyond those reported for other methods for increasing the longevity of organic fluorophores, and those covalently attached to UCNP surface polymers show greater chemical stability than those directly coordinated to the nanocrystal surface. By conjugating other fluorescent chemosensors to UCNPs, these hybrids may be extended to a series of NIR-responsive biosensors for quantifying the dynamic chemical populations critical for cell signaling.
- Published
- 2018
95. Upconverting nanoparticle micro-lightbulbs designed for deep tissue optical stimulation and imaging
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Chamanzar, Maysamreza, Garfield, David J, Iafrati, Jillian, Chan, Emory M, Sohal, Vikaas, Cohen, Bruce E, Schuck, P James, and Maharbiz, Michel M
- Subjects
Engineering ,Physical Sciences ,Biomedical Engineering ,Nanotechnology ,Neurosciences ,Bioengineering ,Affordable and Clean Energy ,(130.3990) Micro-optical devices ,(170.0110) Imaging systems ,(190.7220) Upconversion ,Optical Physics ,Materials Engineering ,Ophthalmology and optometry ,Biomedical engineering ,Atomic ,molecular and optical physics - Abstract
Optical methods for imaging and stimulation of biological events based on the use of visible light are limited to the superficial layers of tissue due to the significant absorption and scattering of light. Here, we demonstrate the design and implementation of passive micro-structured lightbulbs (MLBs) containing bright-emitting lanthanide-doped upconverting nanoparticles (UCNPs) for light delivery deep into the tissue. The MLBs are realized as cylindrical pillars made of Parylene C polymer that can be implanted deep into the tissue. The encapsulated UCNPs absorb near-infrared (NIR) light at λ = 980 nm, which undergoes much less absorption than the blue light in the brain tissue, and then locally emit blue light (1G4→3H6 and 1D2→3F4 transitions) that can be used for optogenetic excitation of neurons in the brain. The 3H4→3H6 transition will result in the emission of higher energy NIR photons at λ = 800 nm that can be used for imaging and tracking MLBs through thick tissue.
- Published
- 2018
96. Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis
- Author
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Fox, Robert J, Coffey, Christopher S, Conwit, Robin, Cudkowicz, Merit E, Gleason, Trevis, Goodman, Andrew, Klawiter, Eric C, Matsuda, Kazuko, McGovern, Michelle, Naismith, Robert T, Ashokkumar, Akshata, Barnes, Janel, Ecklund, Dixie, Klingner, Elizabeth, Koepp, Maxine, Long, Jeffrey D, Natarajan, Sneha, Thornell, Brenda, Yankey, Jon, Bermel, Robert A, Debbins, Josef P, Huang, Xuemei, Jagodnik, Patricia, Lowe, Mark J, Nakamura, Kunio, Narayanan, Sridar, Sakaie, Ken E, Thoomukuntla, Bhaskar, Zhou, Xiaopeng, Krieger, Stephen, Alvarez, Enrique, Apperson, Michelle, Bashir, Khurram, Cohen, Bruce A, Coyle, Patricia K, Delgado, Silvia, Dewitt, L Dana, Flores, Angela, Giesser, Barbara S, Goldman, Myla D, Jubelt, Burk, Lava, Neil, Lynch, Sharon G, Moses, Harold, Ontaneda, Daniel, Perumal, Jai S, Racke, Michael, Repovic, Pavle, Riley, Claire S, Severson, Christopher, Shinnar, Shlomo, Suski, Valerie, Weinstock-Guttman, Bianca, Yadav, Vijayshree, and Zabeti, Aram
- Subjects
Neurosciences ,Neurodegenerative ,Brain Disorders ,Clinical Trials and Supportive Activities ,Autoimmune Disease ,Multiple Sclerosis ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Neurological ,Adult ,Atrophy ,Brain ,Depression ,Diffusion Tensor Imaging ,Disease Progression ,Double-Blind Method ,Female ,Gastrointestinal Diseases ,Headache ,Humans ,Male ,Middle Aged ,Multiple Sclerosis ,Chronic Progressive ,Phosphodiesterase Inhibitors ,Pyridines ,NN102/SPRINT-MS Trial Investigators ,Medical and Health Sciences ,General & Internal Medicine - Abstract
BackgroundThere are limited treatments for progressive multiple sclerosis. Ibudilast inhibits several cyclic nucleotide phosphodiesterases, macrophage migration inhibitory factor, and toll-like receptor 4 and can cross the blood-brain barrier, with potential salutary effects in progressive multiple sclerosis.MethodsWe enrolled patients with primary or secondary progressive multiple sclerosis in a phase 2 randomized trial of oral ibudilast (≤100 mg daily) or placebo for 96 weeks. The primary efficacy end point was the rate of brain atrophy, as measured by the brain parenchymal fraction (brain size relative to the volume of the outer surface contour of the brain). Major secondary end points included the change in the pyramidal tracts on diffusion tensor imaging, the magnetization transfer ratio in normal-appearing brain tissue, the thickness of the retinal nerve-fiber layer, and cortical atrophy, all measures of tissue damage in multiple sclerosis.ResultsOf 255 patients who underwent randomization, 129 were assigned to ibudilast and 126 to placebo. A total of 53% of the patients in the ibudilast group and 52% of those in the placebo group had primary progressive disease; the others had secondary progressive disease. The rate of change in the brain parenchymal fraction was -0.0010 per year with ibudilast and -0.0019 per year with placebo (difference, 0.0009; 95% confidence interval, 0.00004 to 0.0017; P=0.04), which represents approximately 2.5 ml less brain-tissue loss with ibudilast over a period of 96 weeks. Adverse events with ibudilast included gastrointestinal symptoms, headache, and depression.ConclusionsIn a phase 2 trial involving patients with progressive multiple sclerosis, ibudilast was associated with slower progression of brain atrophy than placebo but was associated with higher rates of gastrointestinal side effects, headache, and depression. (Funded by the National Institute of Neurological Disorders and Stroke and others; NN102/SPRINT-MS ClinicalTrials.gov number, NCT01982942 .).
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- 2018
97. Low irradiance multiphoton imaging with alloyed lanthanide nanocrystals.
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Tian, Bining, Fernandez-Bravo, Angel, Najafiaghdam, Hossein, Torquato, Nicole A, Altoe, M Virginia P, Teitelboim, Ayelet, Tajon, Cheryl A, Tian, Yue, Borys, Nicholas J, Barnard, Edward S, Anwar, Mekhail, Chan, Emory M, Schuck, P James, and Cohen, Bruce E
- Subjects
Nanotechnology ,Bioengineering - Abstract
Multiphoton imaging techniques that convert low-energy excitation to higher energy emission are widely used to improve signal over background, reduce scatter, and limit photodamage. Lanthanide-doped upconverting nanoparticles (UCNPs) are among the most efficient multiphoton probes, but even UCNPs with optimized lanthanide dopant levels require laser intensities that may be problematic. Here, we develop protein-sized, alloyed UCNPs (aUCNPs) that can be imaged individually at laser intensities >300-fold lower than needed for comparably sized doped UCNPs. Using single UCNP characterization and kinetic modeling, we find that addition of inert shells changes optimal lanthanide content from Yb3+, Er3+-doped NaYF4 nanocrystals to fully alloyed compositions. At high levels, emitter Er3+ ions can adopt a second role to enhance aUCNP absorption cross-section by desaturating sensitizer Yb3+ or by absorbing photons directly. Core/shell aUCNPs 12 nm in total diameter can be imaged through deep tissue in live mice using a laser intensity of 0.1 W cm-2.
- Published
- 2018
98. The Transformation of Documenting and Coding for Neurologic Hospital Inpatient and Observation Services
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Villanueva, Raissa, Busis, Neil A., Cohen, Bruce H., and Ciccarelli, Luana
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- 2023
- Full Text
- View/download PDF
99. Pharmacogenomic Clinical Support Tools for the Treatment of Depression.
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Baum, Matthew L., Widge, Alik S., Carpenter, Linda L., McDonald, William M., Cohen, Bruce M., and Nemeroff, Charles B.
- Subjects
ATTITUDE testing ,MENTAL depression ,NEW trials ,GENETIC variation - Abstract
Objective: In this review, the authors update the 2018 position statement of the American Psychiatric Association Council of Research Workgroup on Biomarkers and Novel Treatments on pharmacogenomic (PGx) tools for treatment selection in depression. Methods: The literature was reviewed for new clinical trials and meta-analyses, published from 2017 to 2022, of studies using PGx tools for treatment selection in depression. The blinding and control conditions, as well as primary and secondary outcomes and post hoc analyses, were summarized. Results: Eleven new clinical trials and five meta-analyses were identified; all studies had primary outcome measures related to speed or efficacy of treatment response. Three trials (27%) demonstrated efficacy on the primary outcome measure with statistical significance; the three studies used different PGx tools; one study was open-label and the other two were small single-blind trials. Five trials (45%) did not detect efficacy with statistical significance on either primary or secondary outcome measures. Only one trial (9%) used adverse events as a primary outcome measure. All studies had significant limitations; for example, none adopted a fully blinded study design, only two studies attempted to blind the treating clinician, and none incorporated measures to estimate the effectiveness of the blinds or the influence of lack of blinding on the study results. Conclusions: The addition of these new data do not alter the recommendations of the 2018 report, or the advice of the U.S. Food and Drug Administration, that the evidence does not support the use of currently available combinatorial PGx tools for treatment selection in major depressive disorder. Priority efforts for future studies and the development and testing of effective tools include fully blinded study designs, inclusion of promising genetic variants not currently included in any commercially available tests, and investigation of other uses of pharmacogenomics, such as estimating the likelihood of rare adverse drug effects, rather than increasing the speed or magnitude of drug response. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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100. Well-Being in the Nation : A Living Library of Measures to Drive Multi-Sector Population Health Improvement and Address Social Determinants
- Author
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SAHA, SOMAVA, COHEN, BRUCE B., NAGY, JULIA, McPHERSON, MARIANNE E., and PHILLIPS, ROBERT
- Published
- 2020
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