205 research outputs found

    Exploiting the impact of the secretome of MSCs isolated from different tissue sources on neuronal differentiation and axonal growth

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    Cell transplantation using Mesenchymal stem cell (MSC) secretome have recently been presented as a possible free-based therapy for CNS related disorders. MSC secretome is rich in several bio-factors that act synergically towards the repair of damaged tissues, thus making it an ideal candidate for regenerative applications. Great effort is currently being made to map the molecules that compose the MSC secretome. Previous proteomic characterization of the secretome (in the form of conditioned media - CM) of MSCs derived from adipose tissue (ASC), bone-marrow (BMSC) and umbilical cord (HUCPVC) was performed by our group, where proteins relevant for neuroprotection, neurogenic, neurodifferentiation, axon guidance and growth functions were identified. Moreover, we have found significant differences among the expression of several molecules, which may indicate that their therapeutic outcome might be distinct. Having this in mind, in the present study, the neuroregulatory potential of ASC, BMSC and HUCPVC CM in promoting neurodifferentiation and axonal outgrowth was tested in vitro, using human telencephalon neuroprogenitor cells and dorsal root ganglion explants, respectively. The CM from the three MSC populations induced neuronal differentiation from human neural progenitor cells, as well as neurite outgrowth from dorsal root ganglion explants. Moreover, all the MSC populations promoted the same extent of neurodifferentiation, while ASC CM demonstrated higher potential in promoting axonal growth.The authors acknowledge the financial support by Premios Santa Casa Neurociencias - Prize Melo e Castro for Spinal Cord ^ Injury Research (MC-17-2013 and MC-04-2017); Portuguese Foundation for Science and Technology (Doctoral fellowships PDE/ BDE/113596/2015 and SFRH/BD/120124/2016 to R.C Assunçao Silva ~ and B. Mendes-Pinheiro, respectively; Post-doctoral fellowhip to F.G. Teixeira and Patrícia Patrício - SFRH/BPD/118408/2016 and SFRH/BPD/116249/2016; IF Starting Grant to L. Pinto and IF Development Grant to A. J. Salgado); Canada Research Chair in Biomedical Engineering (LAB). This work is funded by national funds through FCT under the scope of grante reference TUBITAK/0007/ 2014. This article has been developed under the scope of the project NORTE-01-0145-FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology, under the scope of the project POCI-01-0145-FEDER-007038. HUCPVCs and ASCs were kindly provided by Prof. John E. Davies (University of Toronto, Canada) and Prof. Jeff Gimble (LaCell Inc, USA).info:eu-repo/semantics/publishedVersio

    A Branch-and-Price Algorithm Enhanced by Decision Diagrams for the Kidney Exchange Problem

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    Kidney paired donation programs allow patients registered with an incompatible donor to receive a suitable kidney from another donor, as long as the latter's co-registered patient, if any, also receives a kidney from a different donor. The kidney exchange problem (KEP) aims to find an optimal collection of kidney exchanges taking the form of cycles and chains. Existing exact solution methods for KEP either are designed for the case where only cyclic exchanges are considered, or can handle long chains but are scalable as long as cycles are short. We develop the first decomposition method that is able to deal with long cycles and long chains for large realistic instances. More specifically, we propose a branch-and-price framework, in which the pricing problems are solved (for the first time in packing problems in a digraph) through multi-valued decision diagrams. Also, we present a new upper bound on the optimal value of KEP, stronger than the one proposed in the literature, which is obtained via our master problem. Computational experiments show superior performance of our method over the state of the art by optimally solving almost all instances in the PrefLib library for multiple cycle and chain lengths

    Tax compliance cost of bumiputera small and medium enterprises in Northern Malaysia

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    This paper explores and measures the level of tax compliance costs among Bumiputera small and medium enterprises in the Northern Region of Malaysia for the year of assessment 2003. The findings revealed that the tax compliance costs have a significant relationship with the paid up capital(size of enterprises). Overall, the tax compliance cost of Bumiputera small and medium enterprises was RM880,110 for the assessment year 2003. Furthermore tax compliance cost of smaller Bumiputera enterprises amounted to RM413,670 while the larger Bumiputera enterprises was RM466,440.The average tax compliance cost is RM22,003. Most of the large Bumiputera enterprises incurred more external tax compliance costs than internal compliance costs (62.34%) compared to the smaller Bumiputera enterprises (37.66%). In contrast, the smaller Bumiputera enterprises incurred more internal tax compliance costs of about 83% as compared to external tax compliance costs (17%). The results also indicated that small Bumiputera enterprises have a higher percentage of tax compliance costs based on tax revenue, which is 2.57 times more compared to large Bumiputera enterprises,which amounted to only 0.46 times

    The degree-restricted random process is far from uniform

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    The degree-restricted random process is a natural algorithmic model for generating graphs with degree sequence D_n=(d_1, \ldots, d_n): starting with an empty n-vertex graph, it sequentially adds new random edges so that the degree of each vertex v_i remains at most d_i. Wormald conjectured in 1999 that, for d-regular degree sequences D_n, the final graph of this process is similar to a uniform random d-regular graph. In this paper we show that, for degree sequences D_n that are not nearly regular, the final graph of the degree-restricted random process differs substantially from a uniform random graph with degree sequence D_n. The combinatorial proof technique is our main conceptual contribution: we adapt the switching method to the degree-restricted process, demonstrating that this enumeration technique can also be used to analyze stochastic processes (rather than just uniform random models, as before).Comment: 32 pages, 3 figure

    Flotsam, Financing and Flotation: Is Canada “Resolution Ready” for Insurance Company Insolvency?

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    Insurance represents almost 2 per cent of Canada’s gross domestic product (GDP), yet there is little public policy discussion regarding the viability of the companies that insure Canadians or about the policyholder protection and resolution regime that underpins the provision of these services. As new products and technology develop, and as the complexity of multinational insurance enterprises increases, new risks pose challenges for Canada’s oversight and policyholder protection regimes. This article provides an overview of the insolvency regime for insurers in Canada, focusing primarily on the federal regime as the exemplar of how Canadian regulators and the insurance industry have built mechanisms for early intervention. It examines the causes of financial distress and the kinds of asset values that may be identified and preserved during insolvency. It explores the regulatory capital requirements imposed on insurers with the goal of safety and soundness of the system. It then examines policyholder protection and insolvency resolution strategies, including the early intervention system, aimed at keeping companies afloat or enabling them to exit the market with as little disruption as possible. It analyses how Canada’s supervisory and resolution system measures up against international standards, and looks at aspects of the system that need improvement and suggests priorities for legislative reform, including clear assignment of responsibility for resolution, treatment of derivatives and provisions to facilitate cross-border proceedings. The article also highlights new complex challenges facing Canadian insurers in terms of solvency risk, including accounting standards changes, climate change risk and cybersecurity

    ARE CANADIAN CYBER SECURITY RELATED LAWS SUFFICIENT TO DEAL WITH THE REALITY OF TODAY’S THREATS

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    Cyber security is one of the growing concerns across the 21st Century world. For the private sector, proper cyber security allows organizations to protect themselves against the increasing threat of cyber-attacks. These businesses play a critical role by implementing robust security infrastructures that ensure, to the extent possible, the protection of personal and corporate data. At the same time, governments have a major role to play in influencing the decisions that organizations make, especially as it relates to customer data. The current privacy and cybersecurity landscape in Canada has developed over time as a way to hold organizations accountable in protecting the customer information that they collect in the course of their business. This analysis considers the research question of whether or not the existing legislative/regulatory framework in Canada is sufficient to deal with the cyber threats being faced by individual corporations. There is both a shared interest and, arguably, responsibility in addressing the risks associated with cyber threats among the government, private sector, and individuals. However, sharing a common interest against a shared threat, while important, does not necessarily override the expectations that businesses and citizens have respecting unfettered access to the Internet. As a result, for the government, the dilemma becomes one of balance; balance between achieving the appropriate level of regulation in order to protect users of the internet and their overall individual liberty to operate in the cyber world

    Pétrogenèse et potentiel économique de la Formation d’Obatogamau, région de Chibougamau, Sous-province de l’Abitibi

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    Les grands ensembles de basaltes présents dans les ceintures de roches vertes archéennes forment des séquences volcaniques de grande très étendue. Ces unités revêtent également une importance économique en raison de leur association commune avec des systèmes minéralisés tels que les sulfures massifs volcanogènes (SMV) et les gisements d’or orogénique. Ces ensembles sont généralement considérés comme homogènes bien que leur hétérogénéité soit peu testée. Les niveaux felsiques qu’ils peuvent contenir sont notamment peu documentés. Parmi ces ensembles de basaltes, certaines unités sont riches en mégacristaux de plagioclase et sont associées spatialement à des suites intrusives anorthositiques dans lesquels les mégacristaux se seraient formés avant l’émission des laves. Le nombre d’exemples appuyant cette hypothèse reste cependant faible et les conditions de formation des mégacristaux sont peu documentées. Outre l’hétérogénéité de ces ensembles et l’origine des mégacristaux de plagioclase, la source mantellique de ces laves est également débattue ; parfois asssimilée à un manteau appauvri et parfois assimilée à un manteau plus primitif. La présente maîtrise se penche sur la Formation d’Obatogamau située dans la région de Chibougamau au sein de la Sous-province de l’Abitibi. Cette formation correspond à un large ensemble de basaltes à mégacristaux de plagioclases en association spatiale avec plusieurs suites intrusives anorthositique. Elle a de plus, été relativement peu étudiée, avec un âge mal contraint et un potentiel économique très peu défini. L’étude visait donc à questionner ces aspects en plus de l’hétérogénéité de la séquence, de l’origine des mégacristaux et de la source mantellique des laves. Elle se base sur une étude de la chimie et de la pétrogenèse des laves après une campagne d’échantillonnage menée sur une zone restreinte où la Formation d’Obatogamau présente une bonne exposition en surface. D’après les données de chimie roche totale, la Formation d’Obatogamau apparaît extrêmement homogène avec l’essentiel des laves correspondant à des basaltes et basaltes andésitiques riches en fer et la plupart des quelques roches plus différenciées située dans la partie supérieure de la séquence de laves. En outre, la chimie des éléments traces indique une source mantellique faiblement appauvrie pour la majorité des laves mafiques. La forte homogénéité de la séquence de laves pourrait indiquer d’importants taux d’effusions limitant les effets de différenciation magmatique ce qui semble être confirmé par les résultats de modélisation pétrogénétique obtenus à l’aide de l’algorithme MELTS. Une unité felsique, probablement volcanique, a été échantillonnée dans un but de datation U-Pb sur zircon, donnant un âge de 2726,2 ± 1,6 Ma similaire aux âges connus pour la Formation de Waconichi, sus-jacente à la Formation d’Obatogamau. Il n’est cependant pas possible d’exclure totalement la possibilité que cette unité soit un filon-couche lié à la Formation de Waconichi. L’ensemble de ces résultats suggère une mise en place rapide de la Formation d’Obatogamau, potentiellement sur une durée inférieure à quelques Ma, ce qui impliquerait un écart d’âge important avec les quelques unités sous-jacentes connues. Les observations réalisées sur le terrain indiquent un nombre limité d’épisodes de quiescence volcanique, matérialisés par des niveaux volcano-sédimentaires de faible épaisseur, cohérent avec une mise en place rapide le la séquence de lave et des taux d’effusion importants. Ceci impliquerait des conditions non favorables aux minéralisations de type SMV dans le secteur d’étude. Les observations pétrographiques et la chimie des amphiboles indique cependant que les laves du secteur étudié présentent un faciès métamorphique situé à la transition entre les schistes verts et les amphibolites suggèrant des conditions favorables pour la génération de fluides métamorphiques. Cela pourrait indiquer un contexte favorable pour les minéralisations de type orogéniques à conditions que des conduits structuraux aient pu permettre la circulation et la canalisation de tels fluides. L’étude des mégacristaux de plagioclase a montré un fort degré de recristallisation qui n’a pas permis d’établir de lien avec les suites intrusives anorthositiques du secteur. Les données de chimie roche totale suggèrent toutefois que certaines coulées à mégacristaux de plagioclase aient pu remobiliser des cumulats d’oxydes de fer-titane, connus pour cristalliser au sein des suites intrusives anorthositiques

    The Global University: The Role of Senior Managers

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    Contributors address the role of senior managers in relation to internationalisation, globalisation, and sustainable development and share how these often overlapping challenges can be addressed. Consideration has been given to a range of potentially competing demands including the relationship between what Paul Luker describes as the 'core mission and values of HE' and what Caruana and Hanstock describe as 'marketisation discourse'. The Global University: The Role of Senior Manager is written by higher education institution senior managers, for HEI senior managers. Supported by HEFCE Leadership, Governance and Management Funding, 'The Global University: the role of senior managers' is a companion publication to 'The Global University: the role of the curriculum'. Many of the contributors are regarded as critical champions of internationalisation in the UK as well as thoughtful strategists in the process of affecting sustainable university-wide change. To provide further food for thought, in addition to the UK contributions, a case study on university-wide approaches to the development of global citizens at the University of British Columbia and a perspective on the barriers affecting the process of internationalisation in Latin American Universities have also been included. Contributors address key concepts from a variety of perspectives and what will quickly become apparent is that the terms are not always translated in quite the same way (a way of seeing is also a way of not seeing) but in spite of this, collectively, considerable insight for moving the agenda forward is provided. At the very least, the publication will serve to inspire debate on what should constitute the vision, mission and values of a global university, within the context of global society. Given the global footprint of universities and the ability of our graduates to influence change in global society, the publication maintains that universities cannot ignore their corporate and social responsibilities: senior managers have a critical role to play as leaders of this agenda and of change that results in positive benefits for a wider stakeholder group

    Rate-Distortion Theory in Coding for Machines and its Application

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    Recent years have seen a tremendous growth in both the capability and popularity of automatic machine analysis of images and video. As a result, a growing need for efficient compression methods optimized for machine vision, rather than human vision, has emerged. To meet this growing demand, several methods have been developed for image and video coding for machines. Unfortunately, while there is a substantial body of knowledge regarding rate-distortion theory for human vision, the same cannot be said of machine analysis. In this paper, we extend the current rate-distortion theory for machines, providing insight into important design considerations of machine-vision codecs. We then utilize this newfound understanding to improve several methods for learnable image coding for machines. Our proposed methods achieve state-of-the-art rate-distortion performance on several computer vision tasks such as classification, instance segmentation, and object detection
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