Exenatide Improves Bone Quality in a Murine Model of Genetically Inherited Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is associated with skeletal complications, including an increased risk of fractures. Reduced blood supply and bone strength may contribute to this skeletal fragility. We hypothesized that long-term administration of Exenatide, a glucagon- like peptide-1 receptor agonist, would improve bone architecture and strength of T2DM mice by increasing blood flow to bone, thereby stimulating bone formation. In this study, we used a model of obesity and severe T2DM, the leptin receptor-deficient db/db mouse to assess alterations in bone quality and hindlimb blood flow and to examine the beneficial effects of 4 weeks administration of Exenatide. As expected, diabetic mice showed marked alterations in bone structure, remodeling and strength, and basal vascular tone compared with lean mice. Exenatide treatment improved trabecular bone mass and architecture by increasing bone formation rate, but only in diabetic mice. Although there was no effect on hindlimb perfusion at the end of this treatment, exenatide administration acutely increased tibial blood flow. While Exenatide treatment did not restore the impaired bone strength, intrinsic properties of the matrix, such as collagen maturity, were improved. The effects of Exenatide on in vitro bone formation were further investigated in primary osteoblasts cultured under high-glucose conditions, showing that Exenatide reversed the impairment in bone formation induced by glucose. In conclusion, Exenatide improves trabecular bone mass by increasing bone formation and could protect against the development of skeletal complications associated with T2DM

Optimized Surface Code Communication in Superconducting Quantum Computers

Quantum computing (QC) is at the cusp of a revolution. Machines with 100 quantum bits (qubits) are anticipated to be operational by 2020 [googlemachine,gambetta2015building], and several-hundred-qubit machines are around the corner. Machines of this scale have the capacity to demonstrate quantum supremacy, the tipping point where QC is faster than the fastest classical alternative for a particular problem. Because error correction techniques will be central to QC and will be the most expensive component of quantum computation, choosing the lowest-overhead error correction scheme is critical to overall QC success. This paper evaluates two established quantum error correction codes---planar and double-defect surface codes---using a set of compilation, scheduling and network simulation tools. In considering scalable methods for optimizing both codes, we do so in the context of a full microarchitectural and compiler analysis. Contrary to previous predictions, we find that the simpler planar codes are sometimes more favorable for implementation on superconducting quantum computers, especially under conditions of high communication congestion.Comment: 14 pages, 9 figures, The 50th Annual IEEE/ACM International Symposium on Microarchitectur

In vivo morphometric and mechanical characterization of trabecular bone from high resolution magnetic resonance imaging

La osteoporosis es una enfermedad ósea que se manifiesta con una menor densidad ósea y el deterioro de la arquitectura del hueso esponjoso. Ambos factores aumentan la fragilidad ósea y el riesgo de sufrir fracturas óseas, especialmente en mujeres, donde existe una alta prevalencia. El diagnóstico actual de la osteoporosis se basa en la cuantificación de la densidad mineral ósea (DMO) mediante la técnica de absorciometría dual de rayos X (DXA). Sin embargo, la DMO no puede considerarse de manera aislada para la evaluación del riesgo de fractura o los efectos terapéuticos. Existen otros factores, tales como la disposición microestructural de las trabéculas y sus características que es necesario tener en cuenta para determinar la calidad del hueso y evaluar de manera más directa el riesgo de fractura. Los avances técnicos de las modalidades de imagen médica, como la tomografía computarizada multidetector (MDCT), la tomografía computarizada periférica cuantitativa (HR-pQCT) y la resonancia magnética (RM) han permitido la adquisición in vivo con resoluciones espaciales elevadas. La estructura del hueso trabecular puede observarse con un buen detalle empleando estas técnicas. En particular, el uso de los equipos de RM de 3 Teslas (T) ha permitido la adquisición con resoluciones espaciales muy altas. Además, el buen contraste entre hueso y médula que proporcionan las imágenes de RM, así como la utilización de radiaciones no ionizantes sitúan a la RM como una técnica muy adecuada para la caracterización in vivo de hueso trabecular en la enfermedad de la osteoporosis. En la presente tesis se proponen nuevos desarrollos metodológicos para la caracterización morfométrica y mecánica del hueso trabecular en tres dimensiones (3D) y se aplican a adquisiciones de RM de 3T con alta resolución espacial. El análisis morfométrico está compuesto por diferentes algoritmos diseñados para cuantificar la morfología, la complejidad, la topología y los parámetros de anisotropía del tejido trabecular. En cuanto a la caracterización mecánica, se desarrollaron nuevos métodos que permiten la simulación automatizada de la estructura del hueso trabecular en condiciones de compresión y el cálculo del módulo de elasticidad. La metodología desarrollada se ha aplicado a una población de sujetos sanos con el fin de obtener los valores de normalidad del hueso esponjoso. Los algoritmos se han aplicado también a una población de pacientes con osteoporosis con el fin de cuantificar las variaciones de los parámetros en la enfermedad y evaluar las diferencias con los resultados obtenidos en un grupo de sujetos sanos con edad similar.Los desarrollos metodológicos propuestos y las aplicaciones clínicas proporcionan resultados satisfactorios, presentando los parámetros una alta sensibilidad a variaciones de la estructura trabecular principalmente influenciadas por el sexo y el estado de enfermedad. Por otra parte, los métodos presentan elevada reproducibilidad y precisión en la cuantificación de los valores morfométricos y mecánicos. Estos resultados refuerzan el uso de los parámetros presentados como posibles biomarcadores de imagen en la enfermedad de la osteoporosis.Alberich Bayarri, Á. (2010). In vivo morphometric and mechanical characterization of trabecular bone from high resolution magnetic resonance imaging [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/8981Palanci

Towards single-cell bioprinting:micropatterning tools for organ-on-chip development

Organs-on-chips (OoCs) hold promise to engineer progressively more human-relevant in vitro models for pharmaceutical purposes. Recent developments have delivered increasingly sophisticated designs, yet OoCs still lack in reproducing the inner tissue physiology required to fully resemble the native human body. This review emphasizes the need to include microarchitectural and microstructural features, and discusses promising avenues to incorporate well-defined microarchitectures down to the single-cell level. We highlight how their integration will significantly contribute to the advancement of the field towards highly organized structural and hierarchical tissues-on-chip. We discuss the combination of state-of-the-art micropatterning technologies to achieve OoCs resembling human-intrinsic complexity. It is anticipated that these innovations will yield significant advances in realization of the next generation of OoC models.</p

Real time web-based toolbox for computer vision

The last few years have been strongly marked by the presence of multimedia data (images and videos) in our everyday lives. These data are characterized by a fast frequency of creation and sharing since images and videos can come from different devices such as cameras, smartphones or drones. The latter are generally used to illustrate objects in different situations (airports, hospitals, public areas, sport games, etc.). As result, image and video processing algorithms have got increasing importance for several computer vision applications such as motion tracking, event detection and recognition, multimedia indexation and medical computer-aided diagnosis methods. In this paper, we propose a real time cloud-based toolbox (platform) for computer vision applications. This platform integrates a toolbox of image and video processing algorithms that can be run in real time and in a secure way. The related libraries and hardware drivers are automatically integrated and configured in order to offer to users an access to the different algorithms without the need to download, install and configure software or hardware. Moreover, the platform offers the access to the integrated applications from multiple users thanks to the use of Docker (Merkel, 2014) containers and images. Experimentations were conducted within three kinds of algorithms: 1. image processing toolbox. 2. Video processing toolbox. 3. 3D medical methods such as computer-aided diagnosis for scoliosis and osteoporosis.&nbsp; These experimentations demonstrated the interest of our platform for sharing our scientific contributions related to computer vision domain. The scientific researchers could be able to develop and share easily their applications fastly and in a safe way

Probing the Unseen Depths of the Hepatic Microarchitecture via Multimodal Microscopy

Multimodal microscopy combines the advantages and strengths of different imaging modalities in order to holistically characterise the organisation of biological organisms and their comprising constituents under healthy and diseased conditions, down to the spatial resolution required to understand the morphology and function of such structures. Given the profound advantages conferred by such an approach, this work broadly aimed to develop and exploit various multimodal and multi-dimensional imaging modalities in a complimentary, combined and/or correlative manner – namely, three-dimensional scanning electron microscopy, transmission electron tomography, bright-field light microscopy, confocal laser scanning microscopy and X-ray micro-computed tomography – in order to characterise and collect new information on the normal and pathological microarchitecture of rodent and human liver tissue in 3-D under various experimental conditions. The data reported in this work includes a comparative analysis of a variety of sample preparation protocols applied to rat liver tissue to determine the suitability of such protocols for the application of serial block-face scanning electron microscopy (SBF-SEM). Next, 3-D modelling and morphometric analysis (utilising the premier SBF-SEM protocol) was performed in order to visualise and quantify key features of the hepatic microarchitecture. We further outline a large-volume correlative light and electron microscopy approach utilising selective molecular probes for confocal laser scanning microscopy (actin, lipids and nuclei), combined with the 3-D ultrastructure of the same structures of interest, as revealed by SBF-SEM (Chapter 2). Development of a straightforward combinatorial sample preparation approach, followed by a swift multimodal imaging approach – combining X-ray micro-computed tomography, bright-field light microscopy and serial section scanning electron microscopy – facilitated the cross correlation of structure-function information on the same sample across diverse length scales (Chapter 3). Next, we outline a novel “silver filler pre-embedding approach” in order to reduce artefactual charging, minimise dataset acquisition time and improve resolution and contrast in rat liver tissue prepared for SBF-SEM (Chapter 4). Next, we employ a complementary imaging approach involving serial section scanning electron microscopy and transmission electron tomography in order to comparatively analyse the structure and morphometric parameters of thousands of normal- and giant mitochondria in human patients diagnosed with non-alcoholic fatty liver disease. In so doing, we reveal functional alterations associated with mitochondrial gigantism and propose a mechanism for their formation (Chapter 5). Finally, the significance of the results obtained, and major scientific advances reported in this work are discussed in-depth against the relevant literature. This is proceeded by the future outlooks and research that remains to be done, followed by the main conclusions of this Ph.D thesis (Chapter 6). In summary, our findings firmly establish the immense importance and value of contemporary multimodal microscopy modalities in modern life science research, for holistically revealing cellular structures along the vast length scales amongst which they exist, under healthy and clinically relevant pathological conditions

Energy challenges for ICT

The energy consumption from the expanding use of information and communications technology (ICT) is unsustainable with present drivers, and it will impact heavily on the future climate change. However, ICT devices have the potential to contribute signi - cantly to the reduction of CO2 emission and enhance resource e ciency in other sectors, e.g., transportation (through intelligent transportation and advanced driver assistance systems and self-driving vehicles), heating (through smart building control), and manu- facturing (through digital automation based on smart autonomous sensors). To address the energy sustainability of ICT and capture the full potential of ICT in resource e - ciency, a multidisciplinary ICT-energy community needs to be brought together cover- ing devices, microarchitectures, ultra large-scale integration (ULSI), high-performance computing (HPC), energy harvesting, energy storage, system design, embedded sys- tems, e cient electronics, static analysis, and computation. In this chapter, we introduce challenges and opportunities in this emerging eld and a common framework to strive towards energy-sustainable ICT