Development of a Reference Wafer for On-Wafer Testing of Extreme Impedance Devices

This paper describes the design, fabrication, and testing of an on-wafer substrate that has been developed specifically for measuring extreme impedance devices using an on-wafer probe station. Such devices include carbon nano-tubes (CNTs) and structures based on graphene which possess impedances in the κ Ω range and are generally realised on the nano-scale rather than the micro-scale that is used for conventional on-wafer measurement. These impedances are far removed from the conventional 50- reference impedance of the test equipment. The on-wafer substrate includes methods for transforming from the micro-scale towards the nano-scale and reference standards to enable calibrations for extreme impedance devices. The paper includes typical results obtained from the designed wafer

C9orf72 repeat expansions cause neurodegeneration in Drosophila through arginine-rich proteins

An expanded GGGGCC repeat in C9orf72 is the most common genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis. A fundamental question is whether toxicity is driven by the repeat RNA itself and/or by dipeptide repeat proteins generated by repeat-associated, non-ATG translation. To address this question we developed in vitro and in vivo models to dissect repeat RNA and dipeptide repeat protein toxicity. Expression of pure repeats in Drosophila caused adult-onset neurodegeneration attributable to poly-(glycine-arginine) proteins. Thus, expanded repeats promoted neurodegeneration through neurotoxic proteins. Expression of individual dipeptide repeat proteins with a non-GGGGCC RNA sequence showed both poly-(glycine-arginine) and poly-(proline-arginine) proteins caused neurodegeneration. These findings are consistent with a dual toxicity mechanism, whereby both arginine-rich proteins and repeat RNA contribute to C9orf72-mediated neurodegeneration

Electrical and network neuronal properties are preferentially disrupted in dorsal, but not ventral, medial entorhinal cortex in a mouse model of Tauopathy

The entorhinal cortex (EC) is one of the first areas to be disrupted in neurodegenerative diseases such as Alzheimer's disease and frontotemporal dementia. The responsiveness of individual neurons to electrical and environmental stimuli varies along the dorsal-ventral axis of the medial EC (mEC) in a manner that suggests this topographical organization plays a key role in neural encoding of geometric space. We examined the cellular properties of layer II mEC stellate neurons (mEC-SCs) in rTg4510 mice, a rodent model of neurodegeneration. Dorsoventral gradients in certain intrinsic membrane properties, such as membrane capacitance and afterhyperpolarizations, were flattened in rTg4510 mEC-SCs, while other cellular gradients [e.g., input resistance (Ri), action potential properties] remained intact. Specifically, the intrinsic properties of rTg4510 mEC-SCs in dorsal aspects of the mEC were preferentially affected, such that action potential firing patterns in dorsal mEC-SCs were altered, while those in ventral mEC-SCs were unaffected. We also found that neuronal oscillations in the gamma frequency band (30-80 Hz) were preferentially disrupted in the dorsal mEC of rTg4510 slices, while those in ventral regions were comparatively preserved. These alterations corresponded to a flattened dorsoventral gradient in theta-gamma cross-frequency coupling of local field potentials recorded from the mEC of freely moving rTg4510 mice. These differences were not paralleled by changes to the dorsoventral gradient in parvalbumin staining or neurodegeneration. We propose that the selective disruption to dorsal mECs, and the resultant flattening of certain dorsoventral gradients, may contribute to disturbances in spatial information processing observed in this model of dementia. SIGNIFICANCE STATEMENT: The medial entorhinal cortex (mEC) plays a key role in spatial memory and is one of the first areas to express the pathological features of dementia. Neurons of the mEC are anatomically arranged to express functional dorsoventral gradients in a variety of neuronal properties, including grid cell firing field spacing, which is thought to encode geometric scale. We have investigated the effects of tau pathology on functional dorsoventral gradients in the mEC. Using electrophysiological approaches, we have shown that, in a transgenic mouse model of dementia, the functional properties of the dorsal mEC are preferentially disrupted, resulting in a flattening of some dorsoventral gradients. Our data suggest that neural signals arising in the mEC will have a reduced spatial content in dementia

Low temperature decreases bone mass in mice: Implications for humans

ObjectivesHumans exhibit significant ecogeographic variation in bone size and shape. However, it is unclear how significantly environmental temperature influences cortical and trabecular bone, making it difficult to recognize adaptation versus acclimatization in past populations. There is some evidence that cold‐induced bone loss results from sympathetic nervous system activation and can be reduced by nonshivering thermogenesis (NST) via uncoupling protein (UCP1) in brown adipose tissue (BAT). Here we test two hypotheses: (1) low temperature induces impaired cortical and trabecular bone acquisition and (2) UCP1, a marker of NST in BAT, increases in proportion to degree of low‐temperature exposure.MethodsWe housed wildtype C57BL/6J male mice in pairs at 26 °C (thermoneutrality), 22 °C (standard), and 20 °C (cool) from 3 weeks to 6 or 12 weeks of age with access to food and water ad libitum (N = 8/group).ResultsCool housed mice ate more but had lower body fat at 20 °C versus 26 °C. Mice at 20 °C had markedly lower distal femur trabecular bone volume fraction, thickness, and connectivity density and lower midshaft femur cortical bone area fraction versus mice at 26 °C (p < .05 for all). UCP1 expression in BAT was inversely related to temperature.DiscussionThese results support the hypothesis that low temperature was detrimental to bone mass acquisition. Nonshivering thermogenesis in brown adipose tissue increased in proportion to low‐temperature exposure but was insufficient to prevent bone loss. These data show that chronic exposure to low temperature impairs bone architecture, suggesting climate may contribute to phenotypic variation in humans and other hominins.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146428/1/ajpa23684.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146428/2/ajpa23684_am.pd

Domino-like transient dynamics at seizure onset in epilepsy

This is the final version. Available on open access from Public Library of Science via the DOI in this recordData Availability: We have made publicly available the 15 epochs of human EEG data containing generalized paroxysms classified as focal onset, and all 15 epochs containing seizures from one individual used in the manuscript, 1252 EEG epochs containing seizures classified as generalized onset and the 6 mouse mEC recordings. All data and the code used for the data analysis and model simulations they can be accessed via DOI 10.17605/OSF.IO/G2EXK.The International League Against Epilepsy (ILAE) groups seizures into “focal”, “generalized” and “unknown” based on whether the seizure onset is confined to a brain region in one hemisphere, arises in several brain region simultaneously, or is not known, respectively. This separation fails to account for the rich diversity of clinically and experimentally observed spatiotemporal patterns of seizure onset and even less so for the properties of the brain networks generating them. We consider three different patterns of domino-like seizure onset in Idiopathic Generalized Epilepsy (IGE) and present a novel approach to classification of seizures. To understand how these patterns are generated on networks requires understanding of the relationship between intrinsic node dynamics and coupling between nodes in the presence of noise, which currently is unknown. We investigate this interplay here in the framework of domino-like recruitment across a network. In particular, we use a phenomenological model of seizure onset with heterogeneous coupling and node properties, and show that in combination they generate a range of domino-like onset patterns observed in the IGE seizures. We further explore the individual contribution of heterogeneous node dynamics and coupling by interpreting in-vitro experimental data in which the speed of onset can be chemically modulated. This work contributes to a better understanding of possible drivers for the spatiotemporal patterns observed at seizure onset and may ultimately contribute to a more personalized approach to classification of seizure types in clinical practice.Engineering and Physical Sciences Research Council (EPSRC)Medical Research Council (MRC

Ethane steam reforming over a platinum/alumina catalyst: effect of sulphur poisoning

In this study we have examined the adsorption of hydrogen sulfide and methanethiol over platinum catalysts and examined the effect of these poisons on the steam reforming of ethane. Adsorption of hydrogen sulfide was measured at 293 and 873 K. At 873 K the adsorbed state of hydrogen sulfide in the presence of hydrogen was SH rather than S, even though the Pt:S ratio was unity. The effect of 11.2 ppm hydrogen sulfide or methanethiol on the steam reforming of ethane was studied at 873 K and 20 barg. Both poisons deactivated the catalyst over a number of hours, but methanethiol was found to be more deleterious, reducing the conversion by almost an order of magnitude, possibly due to the co-deposition of sulfur and carbon. Changes in the selectivity revealed that the effect of sulfur was not uniform on the reactions occurring, with the production of methane reduced proportionally more than the other products, due to the surface sensitivity of the hydrogenolysis and methanation reactions. The water-gas shift reaction was affected to a lesser extent. No regeneration was observed when hydrogen sulfide was removed from the feedstream in agreement with adsorption studies. A slight regeneration was observed when methanethiol was removed from the feed, but this was believed to be due to the removal of carbon rather than sulfur. The overall effect of sulfur poisoning was to reduce activity and enhance hydrogen selectivity

Pasture Feeding in Late Pregnancy Does Not Improve the Performance of Twin-bearing Ewes and Their Lambs

The present study evaluated the effect of controlled ryegrass-white clover herbage availability from day 128 until day 142 of pregnancy in comparison to unrestricted availability, on the performance of twin-bearing ewes of varying body condition score (BCS; 2.0, 2.5, or 3.0) and their lambs. It was hypothesised that under conditions of controlled herbage availability, the performance of lambs born to ewes with a greater BCS would be greater than those born to ewes with a lower BCS. During the period that the nutritional regimens were imposed, the pre- and post-grazing herbage masses of the Control regimen (1,070±69 and 801±30 kg dry matter [DM]/ha) were lower than the ad libitum regimen (1,784±69 and 1,333±33 kg DM/ha; p0.05). The difference in ewe BCSs and back fats observed among body condition groups was maintained throughout pregnancy (p0.05). Ewe BCS group had no effect on lamb live weight at birth or weaning or on maximal heat production (p>0.05). Serum gamma glutamyl transferase concentrations of lambs born to BCS3.0 ewes were higher within 36 hours of birth than lambs born to BCS2.0 ewes and BCS2.5 ewes (51.8±1.9 vs 46.5±1.9 and 45.6±1.9 IU/mL, respectively [p0.05). Lamb survival was the only lamb parameter that showed an interaction between ewe nutritional regimen and ewe BCS whereby survival of lambs born to BCS2.5 and BCS3.0 ewes differed but only within the Control nutritional regimen ewes (p<0.05). These results indicate farmers can provide twin-bearing ewes with pre- and post-grazing ryegrass-white clover herbage covers of approximately 1,100 and 800 kg DM/ha in late pregnancy, provided that herbage covers are 1400 in lactation, without affecting lamb performance to weaning. The present results also indicate that under these grazing conditions, there is little difference in ewe performance within the BCS range of 2.0 to 3.0 and therefore they do not need to be managed separately

Lesion detection in demoscopy images with novel density-based and active contour approaches

<p>Abstract</p> <p>Background</p> <p>Dermoscopy is one of the major imaging modalities used in the diagnosis of melanoma and other pigmented skin lesions. Automated assessment tools for dermoscopy images have become an important field of research mainly because of inter- and intra-observer variations in human interpretation. One of the most important steps in dermoscopy image analysis is the detection of lesion borders, since many other features, such as asymmetry, border irregularity, and abrupt border cutoff, rely on the boundary of the lesion. </p> <p>Results</p> <p>To automate the process of delineating the lesions, we employed Active Contour Model (ACM) and boundary-driven density-based clustering (BD-DBSCAN) algorithms on 50 dermoscopy images, which also have ground truths to be used for quantitative comparison. We have observed that ACM and BD-DBSCAN have the same border error of 6.6% on all images. To address noisy images, BD-DBSCAN can perform better delineation than ACM. However, when used with optimum parameters, ACM outperforms BD-DBSCAN, since ACM has a higher recall ratio.</p> <p>Conclusion</p> <p>We successfully proposed two new frameworks to delineate suspicious lesions with i) an ACM integrated approach with sharpening and ii) a fast boundary-driven density-based clustering technique. ACM shrinks a curve toward the boundary of the lesion. To guide the evolution, the model employs the exact solution <abbrgrp><abbr bid="B27">27</abbr></abbrgrp> of a specific form of the Geometric Heat Partial Differential Equation <abbrgrp><abbr bid="B28">28</abbr></abbrgrp>. To make ACM advance through noisy images, an improvement of the model’s boundary condition is under consideration. BD-DBSCAN improves regular density-based algorithm to select query points intelligently.</p

No Association of COMT (Val158Met) Genotype with Brain Structure Differences between Men and Women

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