Recursos de colección

Caltech Authors (160.010 recursos)

Repository of works by Caltech published authors.

Group = Heritage Medical Research Institute

Mostrando recursos 1 - 20 de 43

  1. Machine learning to design integral membrane channelrhodopsins for efficient eukaryotic expression and plasma membrane localization

    Maranas, Costas D.; Bedbrook, Claire N.; Yang, Kevin K.; Rice, Austin J.; Gradinaru, Viviana; Arnold, Frances H.
    There is growing interest in studying and engineering integral membrane proteins (MPs) that play key roles in sensing and regulating cellular response to diverse external signals. A MP must be expressed, correctly inserted and folded in a lipid bilayer, and trafficked to the proper cellular location in order to function. The sequence and structural determinants of these processes are complex and highly constrained. Here we describe a predictive, machine-learning approach that captures this complexity to facilitate successful MP engineering and design. Machine learning on carefully-chosen training sequences made by structure-guided SCHEMA recombination has enabled us to accurately predict the rare...

  2. Machine learning to design integral membrane channelrhodopsins for efficient eukaryotic expression and plasma membrane localization

    Bedbrook, Claire N.; Yang, Kevin K.; Rice, Austin J.; Gradinaru, Viviana; Arnold, Frances H.
    There is growing interest in studying and engineering integral membrane proteins (MPs) that play key roles in sensing and regulating cellular response to diverse external signals. A MP must be expressed, correctly inserted and folded in a lipid bilayer, and trafficked to the proper cellular location in order to function. The sequence and structural determinants of these processes are complex and highly constrained. Here we describe a predictive, machine-learning approach that captures this complexity to facilitate successful MP engineering and design. Machine learning on carefully-chosen training sequences made by structure-guided SCHEMA recombination has enabled us to accurately predict the rare...

  3. Scanning confocal vibrometer microscope for vibration analysis of energy-harvesting MEMS in wearables

    Kowarsch, Robert; Janzen, Jürgen; Cho, Hyunjun; Choo, Hyuck; Rembe, Christian
    We present a scanning confocal laser-Doppler vibrometer microscope for sensitive, contactless measurement of microelectromechanical systems (MEMS). This systems enables the dynamic analysis up to 3.2 MHz with a lateral resolution of few micrometers. We show measurements on developed MEMS for vocal-energy harvesting in wearables and medical implants. For efficient harvesting a cantilever beam with a serpentine form was designed with a fundamental resonance at 200 Hz. We verified the simulated mode shapes with our vibration measurements. The observed deviations in resonance frequencies between simulation and measurement are due to modelling and manufacturing dissimilarities.

  4. Real-Time In Vivo Intraocular Pressure Monitoring using an Optomechanical Implant and an Artificial Neural Network

    Kim, Kun ho; Lee, Jeong Oen; Du, Juan; Sretavan, David; Choo, Hyuck
    Optimized glaucoma therapy requires frequent monitoring and timely lowering of elevated intraocular pressure (IOP). A recently developed microscale IOP-monitoring implant, when illuminated with broadband light, reflects a pressure-dependent optical spectrum that is captured and converted to measure IOP. However, its accuracy is limited by background noise and the difficulty of modeling non-linear shifts of the spectra with respect to pressure changes. Using an end-to-end calibration system to train an artificial neural network (ANN) for signal demodulation we improved the speed and accuracy of pressure measurements obtained with an optically probed IOP-monitoring implant and make it suitable for real-time in vivo...

  5. Real-Time In Vivo Intraocular Pressure Monitoring using an Optomechanical Implant and an Artificial Neural Network

    Kim, Kun Ho; Lee, Jeong Oen; Du, Juan; Sretavan, David; Choo, Hyuck
    Optimized glaucoma therapy requires frequent monitoring and timely lowering of elevated intraocular pressure (IOP). A recently developed microscale IOP-monitoring implant, when illuminated with broadband light, reflects a pressure-dependent optical spectrum that is captured and converted to measure IOP. However, its accuracy is limited by background noise and the difficulty of modeling non-linear shifts of the spectra with respect to pressure changes. Using an end-to-end calibration system to train an artificial neural network (ANN) for signal demodulation we improved the speed and accuracy of pressure measurements obtained with an optically probed IOP-monitoring implant and make it suitable for real-time in vivo...

  6. Q&A: How can advances in tissue clearing and optogenetics contribute to our understanding of normal and diseased biology?

    Greenbaum, Alon; Jang, Min J.; Challis, Collin; Gradinaru, Viviana
    Mammalian organs comprise a variety of cells that interact with each other and have distinct biological roles. Access to evaluate and perturb intact biological systems at the cellular and molecular levels is essential to fully understand their functioning in normal and diseased conditions, yet technical limitations have constrained most research to small pieces of tissue. Tissue clearing and optogenetics can help overcome this hurdle: tissue clearing affords optical interrogation of whole organs at the molecular level, and optogenetics enables the scalable control and measurement of cellular activity with light. In this Q&A, we delineate recent advances and practical challenges associated...

  7. Q&A: How can advances in tissue clearing and optogenetics contribute to our understanding of normal and diseased biology?

    Greenbaum, Alon; Jang, Min J.; Challis, Collin; Gradinaru, Viviana
    Mammalian organs comprise a variety of cells that interact with each other and have distinct biological roles. Access to evaluate and perturb intact biological systems at the cellular and molecular levels is essential to fully understand their functioning in normal and diseased conditions, yet technical limitations have constrained most research to small pieces of tissue. Tissue clearing and optogenetics can help overcome this hurdle: tissue clearing affords optical interrogation of whole organs at the molecular level, and optogenetics enables the scalable control and measurement of cellular activity with light. In this Q&A, we delineate recent advances and practical challenges associated...

  8. The Jellyfish Cassiopea Exhibits a Sleep-like State

    Nath, Ravi D.; Bedbrook, Claire N.; Abrams, Michael J.; Basinger, Ty; Bois, Justin S.; Prober, David A.; Sternberg, Paul W.; Gradinaru, Viviana; Goentoro, Lea
    Do all animals sleep? Sleep has been observed in many vertebrates, and there is a growing body of evidence for sleep-like states in arthropods and nematodes. Here we show that sleep is also present in Cnidaria, an earlier-branching metazoan lineage. Cnidaria and Ctenophora are the first metazoan phyla to evolve tissue-level organization and differentiated cell types, such as neurons and muscle. In Cnidaria, neurons are organized into a non-centralized radially symmetric nerve net that nevertheless shares fundamental properties with the vertebrate nervous system: action potentials, synaptic transmission, neuropeptides, and neurotransmitters . It was reported that cnidarian soft corals and box...

  9. The Jellyfish Cassiopea Exhibits a Sleep-like State

    Nath, Ravi D.; Bedbrook, Claire N.; Abrams, Michael J.; Basinger, Ty; Bois, Justin S.; Prober, David A.; Sternberg, Paul W.; Gradinaru, Viviana; Goentoro, Lea
    Do all animals sleep? Sleep has been observed in many vertebrates, and there is a growing body of evidence for sleep-like states in arthropods and nematodes. Here we show that sleep is also present in Cnidaria, an earlier-branching metazoan lineage. Cnidaria and Ctenophora are the first metazoan phyla to evolve tissue-level organization and differentiated cell types, such as neurons and muscle. In Cnidaria, neurons are organized into a non-centralized radially symmetric nerve net that nevertheless shares fundamental properties with the vertebrate nervous system: action potentials, synaptic transmission, neuropeptides, and neurotransmitters . It was reported that cnidarian soft corals and box...

  10. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models

    Cekanaviciute, Egle; Yoo, Bryan B.; Runia, Tessel F.; Debelius, Justine W.; Singh, Sneha; Nelson, Charlotte A.; Kanner, Rachel; Bencosme, Yadira; Lee, Yun Kyung; Hauser, Stephen L.; Crabtree-Hartman, Elizabeth; Katz Sand, Ilana; Gacias, Mar; Zhu, Yungjiao; Casaccia, Patrizia; Cree, Bruce A. C.; Knight, Rob; Mazmanian, Sarkis K.; Baranzini, Sergio E.
    The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice. In contrast, Parabacteroides distasonis, which was reduced in MS patients, stimulated antiinflammatory...

  11. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models

    Cekanaviciute, Egle; Yoo, Bryan B.; Runia, Tessel F.; Debelius, Justine W.; Singh, Sneha; Nelson, Charlotte A.; Kanner, Rachel; Bencosme, Yadira; Lee, Yun Kyung; Hauser, Stephen L.; Crabtree-Hartman, Elizabeth; Katz Sand, Ilana; Gacias, Mar; Zhu, Yungjiao; Casaccia, Patrizia; Cree, Bruce A. C.; Knight, Rob; Mazmanian, Sarkis K.; Baranzini, Sergio E.
    The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice. In contrast, Parabacteroides distasonis, which was reduced in MS patients, stimulated antiinflammatory...

  12. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models

    Cekanaviciute, Egle; Yoo, Bryan B.; Runia, Tessel F.; Debelius, Justine W.; Singh, Sneha; Nelson, Charlotte A.; Kanner, Rachel; Bencosme, Yadira; Lee, Yun Kyung; Hauser, Stephen L.; Crabtree-Hartman, Elizabeth; Katz Sand, Ilana; Gacias, Mar; Zhu, Yungjiao; Casaccia, Patrizia; Cree, Bruce A. C.; Knight, Rob; Mazmanian, Sarkis K.; Baranzini, Sergio E.
    The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice. In contrast, Parabacteroides distasonis, which was reduced in MS patients, stimulated antiinflammatory...

  13. Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models

    Cekanaviciute, Egle; Yoo, Bryan B.; Runia, Tessel F.; Debelius, Justine W.; Singh, Sneha; Nelson, Charlotte A.; Kanner, Rachel; Bencosme, Yadira; Lee, Yun Kyung; Hauser, Stephen L.; Crabtree-Hartman, Elizabeth; Katz Sand, Ilana; Gacias, Mar; Zhu, Yungjiao; Casaccia, Patrizia; Cree, Bruce A. C.; Knight, Rob; Mazmanian, Sarkis K.; Baranzini, Sergio E.
    The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice. In contrast, Parabacteroides distasonis, which was reduced in MS patients, stimulated antiinflammatory...

  14. Localization of Microscale Devices In Vivo using Addressable Transmitters Operated as Magnetic Spins

    Monge, Manuel; Lee-Gosselin, Audrey; Shapiro, Mikhail G.; Emami, Azita
    The function of miniature wireless medical devices, such as capsule endoscopes, biosensors and drug-delivery systems, depends critically on their location inside the body. However, existing electromagnetic, acoustic and imaging-based methods for localizing and communicating with such devices suffer from limitations arising from physical tissue properties or from the performance of the imaging modality. Here, we embody the principles of nuclear magnetic resonance in a silicon integrated-circuit approach for microscale device localization. Analogous to the behaviour of nuclear spins, the engineered miniaturized radio frequency transmitters encode their location in space by shifting their output frequency in proportion to the local magnetic...

  15. Preparation of biogenic gas vesicle nanostructures for use as contrast agents for ultrasound and MRI

    Lakshmanan, Anupama; Lu, George J.; Farhadi, Arash; Nety, Suchita P.; Kunth, Martin; Lee-Gosselin, Audrey; Maresca, David; Bourdeau, Raymond W.; Yin, Melissa; Yan, Judy; Witte, Christopher; Malounda, Dina; Foster, F. Stuart; Schröder, Leif; Shapiro, Mikhail G.
    Gas vesicles (GVs) are a unique class of gas-filled protein nanostructures that are detectable at subnanomolar concentrations and whose physical properties allow them to serve as highly sensitive imaging agents for ultrasound and MRI. Here we provide a protocol for isolating GVs from native and heterologous host organisms, functionalizing these nanostructures with moieties for targeting and fluorescence, characterizing their biophysical properties and imaging them using ultrasound and MRI. GVs can be isolated from natural cyanobacterial and haloarchaeal host organisms or from Escherichia coli expressing a heterologous GV gene cluster and purified using buoyancy-assisted techniques. They can then be modified by...

  16. Preparation of biogenic gas vesicle nanostructures for use as contrast agents for ultrasound and MRI

    Lakshmanan, Anupama; Lu, George J.; Farhadi, Arash; Nety, Suchita P.; Kunth, Martin; Lee-Gosselin, Audrey; Maresca, David; Bourdeau, Raymond W.; Yin, Melissa; Yan, Judy; Witte, Christopher; Malounda, Dina; Foster, F. Stuart; Schröder, Leif; Shapiro, Mikhail G.
    Gas vesicles (GVs) are a unique class of gas-filled protein nanostructures that are detectable at subnanomolar concentrations and whose physical properties allow them to serve as highly sensitive imaging agents for ultrasound and MRI. Here we provide a protocol for isolating GVs from native and heterologous host organisms, functionalizing these nanostructures with moieties for targeting and fluorescence, characterizing their biophysical properties and imaging them using ultrasound and MRI. GVs can be isolated from natural cyanobacterial and haloarchaeal host organisms or from Escherichia coli expressing a heterologous GV gene cluster and purified using buoyancy-assisted techniques. They can then be modified by...

  17. Going Deeper: Biomolecular Tools for Acoustic and Magnetic Imaging and Control of Cellular Function

    Piraner, Dan I.; Farhadi, Arash; Davis, Hunter C.; Wu, Di; Maresca, David; Szablowski, Jerzy O.; Shapiro, Mikhail G.
    Most cellular phenomena of interest to mammalian biology occur within the context of living tissues and organisms. However, today’s most advanced tools for observing and manipulating cellular function, based on fluorescent or light-controlled proteins, work best in cultured cells, transparent model species, or small, surgically accessed anatomical regions. Their reach into deep tissues and larger animals is limited by photon scattering. To overcome this limitation, we must design biochemical tools that interface with more penetrant forms of energy. For example, sound waves and magnetic fields easily permeate most biological tissues, allowing the formation of images and delivery of energy for...

  18. Going Deeper: Biomolecular Tools for Acoustic and Magnetic Imaging and Control of Cellular Function

    Piraner, Dan I.; Farhadi, Arash; Davis, Hunter C.; Wu, Di; Maresca, David; Szablowski, Jerzy O.; Shapiro, Mikhail G.
    Most cellular phenomena of interest to mammalian biology occur within the context of living tissues and organisms. However, today’s most advanced tools for observing and manipulating cellular function, based on fluorescent or light-controlled proteins, work best in cultured cells, transparent model species, or small, surgically accessed anatomical regions. Their reach into deep tissues and larger animals is limited by photon scattering. To overcome this limitation, we must design biochemical tools that interface with more penetrant forms of energy. For example, sound waves and magnetic fields easily permeate most biological tissues, allowing the formation of images and delivery of energy for...

  19. Going Deeper: Biomolecular Tools for Acoustic and Magnetic Imaging and Control of Cellular Function

    Piraner, Dan I.; Farhadi, Arash; Davis, Hunter C.; Wu, Di; Maresca, David; Szablowski, Jerzy O.; Shapiro, Mikhail G.
    Most cellular phenomena of interest to mammalian biology occur within the context of living tissues and organisms. However, today’s most advanced tools for observing and manipulating cellular function, based on fluorescent or light-controlled proteins, work best in cultured cells, transparent model species, or small, surgically accessed anatomical regions. Their reach into deep tissues and larger animals is limited by photon scattering. To overcome this limitation, we must design biochemical tools that interface with more penetrant forms of energy. For example, sound waves and magnetic fields easily permeate most biological tissues, allowing the formation of images and delivery of energy for...

  20. Going Deeper: Biomolecular Tools for Acoustic and Magnetic Imaging and Control of Cellular Function

    Piraner, Dan I.; Farhadi, Arash; Davis, Hunter C.; Wu, Di; Maresca, David; Szablowski, Jerzy O.; Shapiro, Mikhail G.
    Most cellular phenomena of interest to mammalian biology occur within the context of living tissues and organisms. However, today’s most advanced tools for observing and manipulating cellular function, based on fluorescent or light-controlled proteins, work best in cultured cells, transparent model species, or small, surgically accessed anatomical regions. Their reach into deep tissues and larger animals is limited by photon scattering. To overcome this limitation, we must design biochemical tools that interface with more penetrant forms of energy. For example, sound waves and magnetic fields easily permeate most biological tissues, allowing the formation of images and delivery of energy for...

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