Positive impact of low-dose, high-energy radiation on bone in partial- and/or full-weightbearing mice

Astronauts traveling beyond low Earth orbit will be exposed to galactic cosmic radiation (GCR); understanding how high energy ionizing radiation modifies the bone response to mechanical unloading is important to assuring crew health. To investigate this, we exposed 4-mo-old female Balb/cBYJ mice to an acute space-relevant dose of 0.5 Gy 56Fe or sham (n = ~8/group); 4 days later, half of the mice were also subjected to a ground-based analog for 1/6 g (partial weightbearing) (G/6) for 21 days. Microcomputed tomography (µ-CT) of the distal femur reveals that 56Fe exposure resulted in 65-78% greater volume and improved microarchitecture of cancellous bone after 21 d compared to sham controls. Radiation also leads to significant increases in three measures of energy absorption at the mid-shaft femur and an increase in stiffness of the L4 vertebra. No significant effects of radiation on bone formation indices are detected; however, G/6 leads to reduced % mineralizing surface on the inner mid-tibial bone surface. In separate groups allowed 21 days of weightbearing recovery from G/6 and/or 56Fe exposure, radiation-exposed mice still exhibit greater bone mass and improved microarchitecture vs. sham control. However, femoral bone energy absorption values are no longer higher in the 56Fe-exposed WB mice vs. sham controls. We provide evidence for persistent positive impacts of high-LET radiation exposure preceding a period of full or partial weightbearing on bone mass and microarchitecture in the distal femur and, for full weightbearing mice only and more transiently, cortical bone energy absorption values

Transformation Based Ensembles for Time Series Classification

Until recently, the vast majority of data mining time series classification (TSC) research has focused on alternative distance measures for 1-Nearest Neighbour (1-NN) classifiers based on either the raw data, or on compressions or smoothing of the raw data. Despite the extensive evidence in favour of 1-NN classifiers with Euclidean or Dynamic Time Warping distance, there has also been a flurry of recent research publications proposing classification algorithms for TSC. Generally, these classifiers describe different ways of incorporating summary measures in the time domain into more complex classifiers. Our hypothesis is that the easiest way to gain improvement on TSC problems is simply to transform into an alternative data space where the discriminatory features are more easily detected. To test our hypothesis, we perform a range of benchmarking experiments in the time domain, before evaluating nearest neighbour classifiers on data transformed into the power spectrum, the autocorrelation function, and the principal component space. We demonstrate that on some problems there is dramatic improvement in the accuracy of classifiers built on the transformed data over classifiers built in the time domain, but that there is also a wide variance in accuracy for a particular classifier built on different data transforms. To overcome this variability, we propose a simple transformation based ensemble, then demonstrate that it improves performance and reduces the variability of classifiers built in the time domain only. Our advice to a practitioner with a real world TSC problem is to try transforms before developing a complex classifier; it is the easiest way to get a potentially large increase in accuracy, and may provide further insights into the underlying relationships that characterise the problem

On Recursive Edit Distance Kernels with Application to Time Series Classification

This paper proposes some extensions to the work on kernels dedicated to string or time series global alignment based on the aggregation of scores obtained by local alignments. The extensions we propose allow to construct, from classical recursive definition of elastic distances, recursive edit distance (or time-warp) kernels that are positive definite if some sufficient conditions are satisfied. The sufficient conditions we end-up with are original and weaker than those proposed in earlier works, although a recursive regularizing term is required to get the proof of the positive definiteness as a direct consequence of the Haussler's convolution theorem. The classification experiment we conducted on three classical time warp distances (two of which being metrics), using Support Vector Machine classifier, leads to conclude that, when the pairwise distance matrix obtained from the training data is \textit{far} from definiteness, the positive definite recursive elastic kernels outperform in general the distance substituting kernels for the classical elastic distances we have tested.Comment: 14 page

Contributions à l’intégration des procédés de fabrication et d'encapsulation d’un commutateur MEMS RF ohmique

Abstract : This dissertation presents studies to resolve process integration problems in the fabrication of packaged radio frequency microelectromechanical system (RF MEMS) ohmic switches with a Au-Ru contact metallurgy and Al-Ge eutectic wafer bonding for wafer-level packaging (WLP). While unpackaged RF MEMS switches have shown promising attributes poor reliability has limited their development into practical products, demanding compatibility with a hermetic sealing solution. The first article, titled ‘Exploring Ru compatibility with Al-Ge eutectic wafer bonding,’ and its supplemental material examine bond impacts associated with the refractory metal ruthenium (Ru). The compatibility of Ru with a wafer bonding process has been virtually unexplored. The main text of this section outlines the results of blanket deposition annealing experiments with Ru, Al and Ge configurations to address concerns of ternary alloy poisoning, melt wettability on Ru, and Ru as a diffusing contaminant in Al and Ge. A brief exploration of the composition process window for Al-Ge alloys contaminated with Ru is made from available phase diagrams, and strong bond outcomes with real product wafers with Ru contacts are presented. The article concludes that Ru has high compatibility within an expected narrow composition process window of marginally reduced melting temperature for Al-Ge alloy. Supplemental material addresses additional process integration problems in the real bond process associated with Ru: alumina thickening, Ru contamination and Al hillock aggravation. These are challenges for the Al surface, which progressively loses bonding ability with Ge through the fabrication process, and can be obviated with unprocessed bonding Al without Ru exposure. The second article, titled ‘Mitigating re-entrant etch profile undercut in Au etch with an aqua regia variant,’ and its supplemental material examine processed Au outcomes and bond-on-contact consequences primarily inflicted on Au. Thermally-stable Au metallization to Si for microswitch contacts in packaged devices is a considerable integration challenge. The main text of this section outlines an etch profile investigation of Au metallization stack variants with adhesion layers to discriminate delamination-based undercutting from galvanic undercutting when using an aqua regia-based solution, showing which mechanism is applicable for this etchant. A brief examination of the electrochemistry of the etchant is made to explain the unusual outcome of mitigated galvanic undercut confirmed by this analysis, with delamination control eliminating or minimizing undercut for thick Au films. In the supplemental material Au surface evolution is tracked across the fabrication process, with the wafer bonding thermal cycle being deemed most significant. Au hillocking and delamination are the primary challenges, and segmentation of Au features is a leading mitigation option that increases the impact of any Au undercut. Together these chapters develop an improved understanding of contact/bond compatibility. Necessary and promising future work for RF MEMS microfabrication and packaging is outlined at the conclusion of this dissertation.Cette thèse présente des études visant à résoudre les problèmes d’intégration de procédés dans la fabrication de commutateurs radiofréquence ohmiques de systèmes microélectromécaniques de (RF MEMS) encapsulés par une métallurgie de contact Au-Ru et un collage eutectique de gaufres Al-Ge pour l'encapsulation au niveau des gaufres (Wafer-Level Packaging, WLP). Bien que les commutateurs MEMS RF non encapsules aient montré des attributs prometteurs, leur faible fiabilité a limité leur développement en produits pratiques, exigeant la compatibilité avec une solution de collage hermétique. Le premier article, intitulé ‹‹Exploring Ru compatibility with Al-Ge eutectic wafer bonding››, et son supplément examinent les effets de liaison associés au ruthénium (Ru), un métal réfractaire. La compatibilité du Ru avec un procédé de collage de gaufres a été très par inexplorée. Le texte principal de cette section présente les résultats d'expériences de recuit des dépôts pleine plaque avec des configurations de Ru, Al et Ge pour répondre aux préoccupations concernant l'empoisonnement des alliages ternaires, la mouillabilité de la masse fondue sur le Ru, et le Ru en tant que contaminant diffusant dans Al et Ge. Une brève exploration de la fenêtre de procédé de composition pour les alliages Al-Ge contaminés par Ru est faite à partir des diagrammes de phase disponibles, et des résultats de collage fort avec des gaufres de produits réels avec des contacts Ru sont présentés. L'article conclut que Ru a une compatibilité élevée dans une fenêtre de procédé de composition étroite attendue de température de fusion marginalement réduite pour l'alliage Al-Ge. Des documents complémentaires traitent de problèmes d'intégration autres dans le procédé de collage réel associés au Ru: épaississement de l'alumine, contamination par le Ru et aggravation de la topographie d'Al. Il s'agit de défis pour la surface de l'aluminium, qui perd progressivement sa capacité de collage avec le Ge au cours du procédé de fabrication, et qui peuvent être évités avec de l'aluminium de collage non traité sans exposition au Ru. Le deuxième article, intitulé ‹‹Mitigating re-entrant etch profile undercut in Au etch with an aqua regia variant››, et son matériel supplémentaire examinent les résultats de la gravure de l'Au et les conséquences de la liaison sur le contact principalement infligées à l'Au. La métallisation thermiquement stable de l'Au sur le Si pour les contacts dans les dispositifs encapsulés est un défi d'intégration considérable. Le texte principal de cette section décrit une étude sur le profil de gravure de variantes d'empilement de métallisation Au avec des couches d'adhérence pour distinguer la sous-coupe basée sur la délamination de la sous-coupe galvanique lors de l'utilisation d'une solution à base d'eau régale, montrant quel mécanisme est applicable pour ce réactif de gravure. Un bref examen de l'électrochimie de l'agent de gravure est effectué pour expliquer le résultat inhabituel de la surgravure galvanique atténuée confirmée par cette analyse, le contrôle de la délamination éliminant ou minimisant la surgravure pour les films d'Au épais. Dans les documents complémentaires, l'évolution de la surface de l'or est suivie tout au long du procédé de fabrication, le cycle thermique de collage des gaufres étant considéré comme le plus important. La formation de bosses et le délaminage de l'or sont les principaux défis à relever, et la segmentation des caractéristiques de l'or est une option d'atténuation importante qui augmente l'impact de toute contre-dépouille de l'or. Ensemble, ces chapitres permettent de mieux comprendre la compatibilité contact/liaison. Les travaux futurs nécessaires et prometteurs pour la microfabrication et le conditionnement des MEMS RF sont présentés en conclusion de cette thèse

Feed-Forward Propagation of Temporal and Rate Information between Cortical Populations during Coherent Activation in Engineered In Vitro Networks.

Transient propagation of information across neuronal assembles is thought to underlie many cognitive processes. However, the nature of the neural code that is embedded within these transmissions remains uncertain. Much of our understanding of how information is transmitted among these assemblies has been derived from computational models. While these models have been instrumental in understanding these processes they often make simplifying assumptions about the biophysical properties of neurons that may influence the nature and properties expressed. To address this issue we created an in vitro analog of a feed-forward network composed of two small populations (also referred to as assemblies or layers) of living dissociated rat cortical neurons. The populations were separated by, and communicated through, a microelectromechanical systems (MEMS) device containing a strip of microscale tunnels. Delayed culturing of one population in the first layer followed by the second a few days later induced the unidirectional growth of axons through the microtunnels resulting in a primarily feed-forward communication between these two small neural populations. In this study we systematically manipulated the number of tunnels that connected each layer and hence, the number of axons providing communication between those populations. We then assess the effect of reducing the number of tunnels has upon the properties of between-layer communication capacity and fidelity of neural transmission among spike trains transmitted across and within layers. We show evidence based on Victor-Purpura's and van Rossum's spike train similarity metrics supporting the presence of both rate and temporal information embedded within these transmissions whose fidelity increased during communication both between and within layers when the number of tunnels are increased. We also provide evidence reinforcing the role of synchronized activity upon transmission fidelity during the spontaneous synchronized network burst events that propagated between layers and highlight the potential applications of these MEMs devices as a tool for further investigation of structure and functional dynamics among neural populations

Discrete Elastic Inner Vector Spaces with Application in Time Series and Sequence Mining

This paper proposes a framework dedicated to the construction of what we call discrete elastic inner product allowing one to embed sets of non-uniformly sampled multivariate time series or sequences of varying lengths into inner product space structures. This framework is based on a recursive definition that covers the case of multiple embedded time elastic dimensions. We prove that such inner products exist in our general framework and show how a simple instance of this inner product class operates on some prospective applications, while generalizing the Euclidean inner product. Classification experimentations on time series and symbolic sequences datasets demonstrate the benefits that we can expect by embedding time series or sequences into elastic inner spaces rather than into classical Euclidean spaces. These experiments show good accuracy when compared to the euclidean distance or even dynamic programming algorithms while maintaining a linear algorithmic complexity at exploitation stage, although a quadratic indexing phase beforehand is required.Comment: arXiv admin note: substantial text overlap with arXiv:1101.431

Combining foods, combining tools: understanding in vivoaroma release and sensory perception of composite foods

To date, most of the published works that have attempted to relate aroma release and sensory perception are far from mimicking the real consumption context, as assessments often do not consider food oral processing during mastication and are performed on single or model foods. A multidisciplinary approach integrating in vivo aroma release, oral processing behaviour, and dynamic sensory methods is needed to have a better understanding of how the release, evolution, and fading of the flavour of real complex food matrices are being perceived during consumption. The research described in this thesis aims to investigate the relative contributions that food structure and its composition and oral processing behaviour have on aroma release and perception of food matrices made up of different components and contrasting textures, so-called composite foods. Results showed that the processes of aroma release and perception of composite foods are multidimensional phenomena and seem to be modulated by cross-modal texturearoma interactions. While aroma release increased when a food was assessed in combination with other foods, consumer’s ability to discriminate between foods was reduced and off flavours and texture deficiencies were masked. Furthermore, the role of oral processing behaviour on the breakdown of the food impacting aroma release and perception was highlighted. The use of a multidisciplinary approach provided more useful and accurate sensory profile representing an ecological, valid food consumption context that will ultimately offer new strategies for successfully developing healthier food products with lower fat and sugar content or elaborated with plant protein, for which sensory acceptability remains a challeng