Three-dimensional scanless holographic optogenetics with temporal focusing (3D-SHOT).

Optical methods capable of manipulating neural activity with cellular resolution and millisecond precision in three dimensions will accelerate the pace of neuroscience research. Existing approaches for targeting individual neurons, however, fall short of these requirements. Here we present a new multiphoton photo-excitation method, termed three-dimensional scanless holographic optogenetics with temporal focusing (3D-SHOT), which allows precise, simultaneous photo-activation of arbitrary sets of neurons anywhere within the addressable volume of a microscope. This technique uses point-cloud holography to place multiple copies of a temporally focused disc matching the dimensions of a neurons cell body. Experiments in cultured cells, brain slices, and in living mice demonstrate single-neuron spatial resolution even when optically targeting randomly distributed groups of neurons in 3D. This approach opens new avenues for mapping and manipulating neural circuits, allowing a real-time, cellular resolution interface to the brain

Regulation of Synapse Development by Activity Dependent Transcription in Inhibitory Neurons

Neuronal activity and subsequent calcium influx activates a signaling cascade that causes transcription factors in the nucleus to rapidly induce an early-response program of gene expression. This early-response program is composed of transcriptional regulators that in turn induce transcription of late-response genes, which are enriched for regulators of synaptic development and plasticity that act locally at the synapse

Precise multimodal optical control of neural ensemble activity.

Understanding brain function requires technologies that can control the activity of large populations of neurons with high fidelity in space and time. We developed a multiphoton holographic approach to activate or suppress the activity of ensembles of cortical neurons with cellular resolution and sub-millisecond precision. Since existing opsins were inadequate, we engineered new soma-targeted (ST) optogenetic tools, ST-ChroME and IRES-ST-eGtACR1, optimized for multiphoton activation and suppression. Employing a three-dimensional all-optical read-write interface, we demonstrate the ability to simultaneously photostimulate up to 50 neurons distributed in three dimensions in a 550 × 550 × 100-µm3 volume of brain tissue. This approach allows the synthesis and editing of complex neural activity patterns needed to gain insight into the principles of neural codes

Barbara Strozzi and The Pleasures of Euterpe

This dissertation seeks to close the gaps in research on Barbara Strozzi by presenting modern transcriptions of eight cantatas from Opus 7, Diporti di Euterpe: ‘Sino alla morte’ (#1), ‘Fin che to spiri’ (#3), ‘Non volete ch\u27io mi dolga?’ (#5), ‘Cosi non la voglio’ (#6), ‘Tradimento’ (#9), ‘Basta cosi’ (#11), ‘Che v\u27ho fatto’ (#14) and ‘Non occorre’ (#15). These works have not been previously available for the modern performer. Chosen to demonstrate formal variety, these works reveal thematic and textual connections within the opus as well as demonstrating the evolution of the protagonist\u27s state of mind. In-depth analysis of the first cantata, and a translation and discussion of the entire opus is supported by two analytical charts. These serve to illuminate the rhetorical derivation of Strozzi\u27s wide variety of compositional techniques, highly influenced by the composers Claudio Monteverdi and Pier Francesco Cavalli. To understand the complex ideology of Barbara Strozzi, I have discussed the interwoven construction of her life, poetry and music. Strozzi\u27s public persona was created through musical performances, a published debate, written reviews and a portrait. I investigate this image of Barbara within the context of seventeenth-century Venice, and the larger early-Baroque society spawned by the Medicis and their elite artistic, literary and scientific employees. This cultural milieu, which juxtaposed Roman Catholic Church practice with Greek revival, determined Strozzi\u27s spiritual, personal and civic identity. My thesis also investigates the influence upon Barbara of other prominent women, including painter Artemesia Gentileschi, poet Veronica Franco and nun Arcangela Tarabotti. Strozzi\u27s life and art were also molded by contemporary Venetian librettists, the foremost of whom was her adoptive father, Giulio Strozzi. I investigate these Marinisti concepts which influenced Barbara\u27s own poetry, the greatest part of her texts. I include a brief discussion of Strozzi\u27s entire output, including excerpts of musical scores and annotations to recordings. Strozzi\u27s musical settings, although in the chamber genre, are more closely related to early seventeenth-century opera. Most of the composer\u27s music is set for her own soprano voice, primarily representing her self-identification as a new Sappho: a channel for the muse of lyric poetry, Euterpe and the goddess of love, Aphrodite. Although Strozzi\u27s public image was often associated with the erotic, her life and compositions disclose a highly educated woman, who was possessed of a developed spirituality, manifest throughout her oevre. Performance practice is viewed through the lens of publications from the Baroque era.

Crystallography and Microstructure of Manganese-Sulfide Inclusions in Steel.

Development of preferred orientation in manganese sulfide inclusions in hot-rolled steel was studied by electron diffraction. Specimens of resulfurized steel were examined as-cast, and at plane strains of 0.5, 1.0, and 1.5 using selected-area electron diffraction in a transmission electron microscope. Specimens were made electron transparent by a combination of mechanical grinding and ion-beam milling. Diffraction patterns and specimen tilts were measured and a microcomputer was used to plot inverse pole figures, and quantitatively evaluate the degree of crystallographic texture. It was found that the inclusions in the as-cast specimen had an essentially r and om orientation but plane strain brought about a texture that was most intense at a strain of 1.0. Clustering of the rolling direction, rolling plane normal, and transverse direction about the indicates a {100} ideal orientation. The behavior of the texture intensity as a function of strain is attributed to strain hardening of the primary {110}(' ) slip systems. Final shape of the inclusions was also studied as a function of inclusion orientation. It was found that there is only a moderate correlation between shape and orientation. This result is attributed, first to the fact that many as-cast inclusions are not round but are created elongated by being forced between dendrite arms. Also, the resolved shear stresses on the preferred slip planes cannot drop to zero under the normal stresses that lead to plane strain, as they can under uniaxial compression. Microstructures of as-cast and hot-rolled inclusions were studied by electron and light microscopy. As-cast inclusions frequently contained iron-rich, possibly iron-oxide, cores with a very fine grain size. Deformed inclusions showed a cold-worked and recovered structure consisting of dislocations, subgrains, low-angle boundaries, and precipitate particles in many places. Twins were observed occasionally, but not frequently enough to be considered an important deformation mechanism.Ph.D.Engineering, Materials scienceUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/158873/1/8215042.pd

HRTEM image simulations for the study of ultra-thin gate oxides

We have performed high resolution transmission electron microscope (HRTEM) image simulations to qualitatively assess the visibility of various structural defects in ultra-thin gate oxides of MOSFET devices, and to quantitatively examine the accuracy of HRTEM in performing gate oxide metrology. Structural models contained crystalline defects embedded in an amorphous 16 {angstrom}-thick gate oxide. Simulated images were calculated for structures viewed in cross-section. Defect visibility was assessed as a function of specimen thickness and defect morphology, composition, size and orientation. Defect morphologies included asperities lying on the substrate surface, as well as ''bridging'' defects connecting the substrate to the gate electrode. Measurements of gate oxide thickness extracted from simulated images were compared to actual dimensions in the model structure to assess TEM accuracy for metrology. The effects of specimen tilt, specimen thickness, objective lens defocus and coefficient of spherical aberration (C{sub s}) on measurement accuracy were explored for nominal 10{angstrom} gate oxide thickness. Results from this work suggest that accurate metrology of ultra-thin gate oxides (i.e. limited to several per cent error) is feasible on a consistent basis only by using a C{sub s}-corrected microscope. However, fundamental limitations remain for characterizing defects in gate oxides using HRTEM, even with the new generation of C{sub s}-corrected microscopes

HRTEM image simulations for gate oxide metrology

High resolution transmission electron microscopy (HRTEM) has found extensive use in the semiconductor industry for performing device metrology and characterization. However, shrinking device dimensions (gate oxides are rapidly approaching 10{angstrom}) present challenges to the use of HRTEM for many applications, including gate oxide metrology. In this study, we performed HRTEM image simulations of a MOSFET device to examine the accuracy of HRTEM in measuring gate oxide thickness. Length measurements extracted from simulated images were compared to actual dimensions in the model structure to assess TEM accuracy. The effects of specimen tilt, specimen thickness, objective lens defocus and coefficient of spherical aberration (C{sub s}) on measurement accuracy were explored for nominal 10{angstrom} and 16{angstrom} gate oxide thicknesses. The gate oxide was modeled as an amorphous silicon oxide situated between a gate electrode and substrate, both modeled as single crystal Si(100). Image simulations of the sandwich structure were performed in cross-section (with Si[110] parallel to beam direction) using the multislice approximation for a 200 kV microscope with C{sub s}=0.5mm. Amorphous slices were added to the top and bottom of the specimen to simulate the amorphization that occurs during typical specimen preparation. The actual gate oxide thickness, T, is defined as the distance between the bounding Si atoms in the model structure. The gate oxide thickness was also measured directly in pixels from the simulated image. We use a statistical routine to calculate the standard deviation in pixel intensity for each horizontal row (or y-coordinate) in the simulated image. Local minima in the standard deviation, which correspond to low-intensity regions between Si[110] dumbbells, were used to calibrate the image length scale. The measured gate oxide thickness was then compared to the actual (model) thickness to assess accuracy for a variety of microscope and specimen conditions. Results reveal no consistent trends in measurement accuracy as a function of specimen thickness, specimen tilt, or objective lens defocus