Analog VLSI Circuits for Biosensors, Neural Signal Processing and Prosthetics

Stroke, spinal cord injury and neurodegenerative diseases such as ALS and Parkinson's debilitate their victims by suffocating, cleaving communication between, and/or poisoning entire populations of geographically correlated neurons. Although the damage associated with such injury or disease is typically irreversible, recent advances in implantable neural prosthetic devices offer hope for the restoration of lost sensory, cognitive and motor functions by remapping those functions onto healthy cortical regions. The research presented in this thesis is directed toward developing enabling technology for totally implantable neural prosthetics that could one day restore lost sensory, cognitive and motor function to the victims of debilitating neural injury or disease. There are three principal components to this work. First, novel integrated biosensors have been designed and implemented to transduce weak extra-cellular electrical potentials and optical signals from cells cultured directly on the surface of the sensor chips, as well as to manipulate cells on the surface of these chips. Second, a method of detecting and identifying stereotyped neural signals, or action potentials, has been mapped into silicon circuits which operate at very low power levels suitable for implantation. Third, as one small step towards the development of cognitive neural implants, a learning silicon synapse has been implemented and a neural network application demonstrated. The original contributions of this dissertation include: * A contact image sensor that adapts to background light intensity and can asynchronously detect statistically significant optical events in real-time; * Programmable electrode arrays for enhanced electrophysiological recording, for directing cellular growth, for site-specific in situ bio-functionalization, and for analyte and particulate collection; * Ultra-low power, programmable floating gate template matching circuits for the detection and classification of neural action potentials; * A two transistor synapse that exhibits spike timing dependent plasticity and can implement adaptive pattern classification and silicon learning

Interstellar Deuterium, Nitrogen, and Oxygen Abundances Toward BD +28 4211: Results from the Far Ultraviolet Spectroscopic Explorer

High resolution far-ultraviolet spectra of the O-type subdwarf BD +28 4211 were obtained with the Far Ultraviolet Spectroscopic Explorer (FUSE) to measure the interstellar deuterium, nitrogen, and oxygen abundances in this direction. The interstellar D I transitions are analyzed down to Lyman iota at 920.7 A. The star was observed several times at different target offsets in the direction of spectral dispersion. The aligned and coadded spectra have high signal-to-noise ratios (S/N =50-100). D I, N I, and O I transitions were analyzed with curve-of-growth and profile fitting techniques. A model of interstellar molecular hydrogen on the line of sight was derived from H2 lines in the FUSE spectra and used to help analyze some features where blending with H2 was significant. The H I column density was determined from high resolution HST/STIS spectra of Lyman alpha to be log(N HI) = 19.846+/-0.035 (2 sigma), which is higher than is typical for sight lines in the local ISM studied for D/H. We found that D/H =(1.39+/-0.21) E-5 (2 sigma) and O/H = (2.37+/-0.55) E-4 (2 sigma). O/H toward BD +28 4211 appears to be significantly below the mean O/H ratio for the ISM and the Local Bubble.Comment: 33 pages, 12 figures, accepted for publication in The Astrophysical Journal Supplemen

Ultrafast Coherent Generation of Hot Electrons Studied via Band-to-Acceptor Luminescence in GaAs

The distribution of hot electrons excited with femtosecond laser pulses is studied via spectrally resolved band-to-acceptor luminescence. Our data demonstrate for the first time that the coherent coupling between the laser pulse and the interband polarization strongly influences the initial carrier distribution. The energetic width of carrier generation is broadened due to rapid phase-breaking scattering events. Theoretical results from a Monte Carlo solution of the semiconductor Bloch equations including on the same kinetic level coherent and incoherent phenomena, are in excellent agreement with the experimental data

Beyond Environmental Regulatory Fragmentation: Signs of Integration in the Case of the Great Lakes Basin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72007/1/j.1468-0491.1995.tb00197.x.pd

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

Risk of diabetes after para-aortic radiation for testicular cancer

Background: While the risk of diabetes is increased following radiation exposure to the pancreas among childhood cancer survivors, its association among testicular cancer (TC) survivors has not been investigated. Methods: Diabetes risk was studied in 2998 1-year TC survivors treated before 50 years of age with orchidectomy with/without radiotherapy between 1976 and 2007. Diabetes incidence was compared with general population rates. Treatment-specific risk of diabetes was assessed using a case–cohort design. Results: With a median follow-up of 13.4 years, 161 TC survivors were diagnosed with diabetes. Diabetes risk was not increased compared to general population rates (standardised incidence ratios (SIR): 0.9; 95% confidence interval (95% CI): 0.7–1.1). Adjusted for age, para-aortic radiotherapy was associated with a 1.66-fold (95% CI: 1.05–2.62) increased diabetes risk compared to no radiotherapy. The excess hazard increased with 0.31 with every 10 Gy increase in the prescribed radiation dose (95% CI: 0.11–0.51, P = 0.003, adjusted for age and BMI); restricted to irradiated patients the excess hazard increased with 0.33 (95% CI: −0.14 to 0.81, P = 0.169) with every 10 Gy increase in radiation dose. Conclusion: Compared to surgery only, para-aortic irradiation is associated with increased diabetes risk among TC survivors