Efficient transduction and optogenetic stimulation of retinal bipolar cells by a synthetic adeno-associated virus capsid and promoter

In this report, we describe the development of a modified adeno-associated virus (AAV) capsid and promoter for transduction of retinal ON-bipolar cells. The bipolar cells, which are post-synaptic to the photoreceptors, are important retinal targets for both basic and preclinical research. In particular, a therapeutic strategy under investigation for advanced forms of blindness involves using optogenetic molecules to render ON-bipolar cells light-sensitive. Currently, delivery of adequate levels of gene expression is a limiting step for this approach. The synthetic AAV capsid and promoter described here achieves high level of optogenetic transgene expression in ON-bipolar cells. This evokes high-frequency (∼100 Hz) spiking responses in ganglion cells of previously blind, rd1, mice. Our vector is a promising vehicle for further development toward potential clinical use

REM Sleep and the emotional brain

Thesis (S.M. in Science Writing)--Massachusetts Institute of Technology, Dept. of Humanities, Graduate Program in Science Writing, 2012.Cataloged from PDF version of thesis.Includes bibliographical references (p. 43-47).Sleep and emotion have been linked since the discovery of rapid eye movement (REM) sleep sixty years ago. Sleep, in particular REM sleep and the dreams it harbors, seems to modulate mood, restoring stability to the weary mind. Scientists have struggled to understand this link through the biological study of the brain, the psychological study of dreaming, and the clinical study of how sleep is affected by psychiatric illness. This thesis examines the history of sleep research in terms of its relationship to emotional processing, both from the physiological and the psychological perspective. We are introduced to the scientists who discovered REM in 1953, to those who tracked the links between the biochemistry of mood and of sleep, and to contemporary researchers who are exploring the link between sleep and mood using brain-scanners and electrodes to study the dreaming brain, and the sleep and dreaming of patients with mood disorders. On our journey we will experience both the progress sleep research has made this century, and the enduring mystery of why humans sleep and dream.by Taylor McGowin Beck.S.M.in Science Writin

General-purpose and special-purpose visual systems

The information that eyes supply supports a wide variety of functions, from the guidance systems that enable an animal to navigate successfully around the environment, to the detection and identification of predators, prey, and conspecifics. The eyes with which we are most familiar the single-chambered eyes of vertebrates and cephalopod molluscs, and the compound eyes of insects and higher crustaceans allow these animals to perform the full range of visual tasks. These eyes have evidently evolved in conjunction with brains that are capable of subjecting the raw visual information to many different kinds of analysis, depending on the nature of the task that the animal is engaged in. However, not all eyes evolved to provide such comprehensive information. For example, in bivalve molluscs we find eyes of very varied design (pinholes, concave mirrors, and apposition compound eyes) whose only function is to detect approaching predators and thereby allow the animal to protect itself by closing its shell. Thus, there are special-purpose eyes as well as eyes with multiple functions

Binocular Interactions in Glaucoma Patients With Nonoverlapping Visual Field Defects:Contrast Summation, Rivalry, and Phase Combination

PURPOSE: In glaucoma, visual field defects in the left and right eye may be non-overlapping, resulting in an intact binocular visual field. In clinical management, these patients are often considered to have normal vision. However, visual performance also relies on binocular processing. The aim of this study was to evaluate binocular visual functions in glaucoma patients with intact binocular visual field, normal visual acuity, and stereoscopy. METHODS: We measured in 10 glaucoma patients and 12 age-similar controls: (1) monocular and binocular contrast sensitivity functions (CSF) using a modified quick CSF test to assess binocular contrast summation, (2) dominance during rivalry, and (3) contrast ratio at balance point with a binocular phase combination test. A mirror stereoscope was used to combine the left and right eye image (each 10° horizontally by 12° vertically) on a display. RESULTS: Area under the monocular and binocular CSF was lower in glaucoma compared to healthy (P < 0.001), but the binocular contrast summation ratio did not differ (P = 0.30). For rivalry, the percentage of time of mixed percept was 9% versus 18% (P = 0.056), the absolute difference of the percentage of time of dominance between the two eyes 19% versus 10% (P = 0.075), and the rivalry rate 8.2 versus 12.1 switches per minute (P = 0.017) for glaucoma and healthy, respectively. Median contrast ratio at balance point was 0.66 in glaucoma and 1.03 in controls (P = 0.011). CONCLUSIONS: Binocular visual information processing deficits can be found in glaucoma patients with intact binocular visual field, normal visual acuity, and stereoscopy

Binocular Interactions in Glaucoma Patients With Nonoverlapping Visual Field Defects:Contrast Summation, Rivalry, and Phase Combination

PURPOSE. In glaucoma, visual field defects in the left and right eye may be non-overlapping, resulting in an intact binocular visual field. In clinical management, these patients are often considered to have normal vision. However, visual performance also relies on binocular processing. The aim of this study was to evaluate binocular visual functions in glaucoma patients with intact binocular visual field, normal visual acuity, and stereoscopy.METHODS. We measured in 10 glaucoma patients and 12 age-similar controls: (1) monocular and binocular contrast sensitivity functions (CSF) using a modified quick CSF test to assess binocular contrast summation, (2) dominance during rivalry, and (3) contrast ratio at balance point with a binocular phase combination test. A mirror stereoscope was used to combine the left and right eye image (each 10 degrees horizontally by 12 degrees vertically) on a display.RESULTS. Area under the monocular and binocular CSF was lower in glaucoma compared to healthy (P &lt; 0.001), but the binocular contrast summation ratio did not differ (P = 0.30). For rivalry, the percentage of time of mixed percept was 9% versus 18% (P = 0.056), the absolute difference of the percentage of time of dominance between the two eyes 19% versus 10% (P = 0.075), and the rivalry rate 8.2 versus 12.1 switches per minute (P = 0.017) for glaucoma and healthy, respectively. Median contrast ratio at balance point was 0.66 in glaucoma and 1.03 in controls (P = 0.011).CONCLUSIONS. Binocular visual information processing deficits can be found in glaucoma patients with intact binocular visual field, normal visual acuity, and stereoscopy.</p

Design and Application of Lidar Systems and Electric Bicycle Modeling for Transportation Safety

As the importance of reducing dependency on fossil fuels increases, the use of bicyclesand electric bicycles (e-bikes) can provide a sustainable and viable alternative for single passenger commuters. The general population’s reluctance to transition to bikes and e-bikes is, in part, due to safety concerns and general mobility. However, by designing, modeling, and testing solutions aimed at reducing weaknesses inherent to cycling, perhaps these fears can be lessened. This thesis describes risks currently involved with cycling and supplies potential solutions in the form of blind-spot and road surface monitoring, as well as modeling the body forces and the power consumption of an e-bike in motion. Chapter 1 introduces the inherent dangers facing bikes and e-bikes when compared to vehicles and discusses methods for improving their safety. Additionally, it highlights the difference between and benefits of preventative safety features for use with cycling. Furthermore, this chapter introduces the use of lidar along with its further use and potential for transportation uses. In Chapter 2, e-bike blind-spot monitoring is designed and tested using a low-cost two-dimensional lidar system. It describes improvements made from previous versions along with the hardware, software, and capabilities of the design. Testing shows its ability to determine distances to objects while alerting the rider, as well as identifying potential improvements for future systems. Chapter 3 describes the hardware and software of a hand-held, portable, low-cost three-dimensional (3-D) lidar system designed for road surface monitoring. Thorough testing shows the lidar system’s ability to create a 3-D point cloud recreation of a pothole in the road. It also identifies improvements made from a previous version and what augmentations should be made in future systems. Additionally, this chapter includes a comparison to commercially available lidar systems. Chapter 4 describes the theoretical equations used to model the motion, body force, power consumption, and battery capacity of an e-bike while in use. Furthermore, by knowing road and weather conditions, e-bike design, combined weight and size of the rider and e-bike, the model can predict battery pack behavior and state of charge. Chapter 5 details experimental testing of the theoretical model described in Chapter 4. By estimating physical properties from available literature and thoroughly measuring e-bike motion, wind conditions, and route, the model can be compared to the actual battery voltage that was recorded throughout the tested routes. Additional modifications are made to the model to account for discretization of measured data and the state of health of the battery pack to better reflect the collected data

Engineering study for a mass memory system for advanced spacecrafts Final report, 1 Dec. 1969 - 1 Jul. 1970

Mass memory system for advanced spacecraf

Parametric studies on pattern recognition mechanisms in human vision

Imperial Users onl

A Large-Scale Model of Spatio-Temporal Patterns of Excitation and Inhibition Evoked by the Horizontal Network in Layer 2/3 of the Visual Cortex

Cortical processing of even the most elementary visual stimuli can result in the propagation of information over significant spatiotemporal scales. To fully understand the impact of such phenomena it is essential to consider the influence of both the neural circuitry beyond the immediate retinotopic location of the stimulus, including pre-cortical areas, and the temporal components of stimulus driven activity that may persist over significant periods. Two computational modelling studies have been performed to explore these phenomena and are reported in this thesis. I) The plexus of long and short range lateral connections is a prominent feature of the layer 2/3 microcircuit in primary visual cortex. Despite the scope for possible functionality, the interdependence of local and long range circuits is still unclear. Spatiotemporal patterns of activity appear to be shaped by the underlying connectivity architecture and strong inhibition. A modelling study has been conducted to capture population activity that has been observed in vitro using voltage sensitive dyes. The model demonstrates that the precise spatiotemporal spread of activity seen in the cortical slice results from long range connections that target specific orientation domains whilst distinct regions of suppressed activity are shown to arise from local isotropic axonal projections. Distal excitatory activity resulting from long range axons is shaped by local interneurons similarly targeted by such connections. It is shown that response latencies of distal excitation are strongly influenced by frequency dependent facilitation and low threshold characteristics of interneurons. Together, these results support hypotheses made following experimental observations in vitro and clearly illustrate the underlying mechanisms. However, predictions by the model suggest that in vivo conditions give rise to markedly different spatiotemporal activity. Furthermore, opposing data in the literature regarding inter-laminar connectivity give rise to profoundly different spatiotemporal patterns of activity in cortex. 2) The second computational modelling study considers simple moving stimuli. These stimuli are implicated in the 'motion streak' phenomenon whereby the movement of a visual feature can give rise to trajectory information that is not explicitly present. Published experimental data of an in vivo study in the cat has shown that a single small light square moving stimulus elicits activity in populations of neurons in primary visual cortex that are selective for orientations parallel to stimulus trajectory (Jancke 2000). In more recent, unpublished data, this work is extended to consider long term persistent cortical activity that is generated by similar stimuli. These data indicate that following initial cortical activation that appears to result directly from the stimulus, iso-orientation domains display persistent activity. Furthermore, initial activity is broadly tuned with respect to orientation whilst later activity is strongly selective for orientations that are parallel to the stimulus trajectory. Currently the generative processes involved have not been clearly defined. Hence the proposed thesis will contribute to a more complete understanding of the mechanisms responsible for such cortical representations of moving visual stimuli. More specifically this will be achieved by a large scale mean field model that will enable a thorough investigation of the anatomical and electrophysiological elements concerned with the observed spatiotemporal dynamic behaviour and will represent a significant region of cortex. In conjunction, an existing computational model of the retina will be integrated. In doing so this thesis will offer the notion that certain cortical representations are inextricably linked with earlier stages of the visual pathway. As such consideration of retinal processing is fundamental to the understanding cortical functions and failure to do so can only result in erroneous conclusions

Recommendations to the Social Security Administration on the Design of the Mental Health Treatment Study

Many beneficiaries with mental illness who have a strong desire to work nevertheless continue to seek the protection and security of disability benefits, not only because of the income such benefits provide but also for the health care coverage that comes with it. Further complicating matters is that few jobs available to people with mental illnesses have mental health care coverage, forcing individuals to choose between employment and access to care. These barriers, coupled with the limited treatment options and negative employer attitudes and even discrimination when it comes to employing people with serious metal illness, help "explain" the very rates of low labor force participation among people with psychiatric disabilities