8,641 research outputs found
An Online Resource Scheduling for Maximizing Quality-of-Experience in Meta Computing
Meta Computing is a new computing paradigm, which aims to solve the problem
of computing islands in current edge computing paradigms and integrate all the
resources on a network by incorporating cloud, edge, and particularly
terminal-end devices. It throws light on solving the problem of lacking
computing power. However, at this stage, due to technical limitations, it is
impossible to integrate the resources of the whole network. Thus, we create a
new meta computing architecture composed of multiple meta computers, each of
which integrates the resources in a small-scale network. To make meta computing
widely applied in society, the service quality and user experience of meta
computing cannot be ignored. Consider a meta computing system providing
services for users by scheduling meta computers, how to choose from multiple
meta computers to achieve maximum Quality-of-Experience (QoE) with limited
budgets especially when the true expected QoE of each meta computer is not
known as a priori? The existing studies, however, usually ignore the costs and
budgets and barely consider the ubiquitous law of diminishing marginal utility.
In this paper, we formulate a resource scheduling problem from the perspective
of the multi-armed bandit (MAB). To determine a scheduling strategy that can
maximize the total QoE utility under a limited budget, we propose an upper
confidence bound (UCB) based algorithm and model the utility of service by
using a concave function of total QoE to characterize the marginal utility in
the real world. We theoretically upper bound the regret of our proposed
algorithm with sublinear growth to the budget. Finally, extensive experiments
are conducted, and the results indicate the correctness and effectiveness of
our algorithm
Targeting the glycation defenses as a protective strategy for Parkinson's disease
Tese de mestrado em Biologia Molecular e Genética, apresentada à Universidade de Lisboa, através da Faculdade de Ciências, 2017O aumento da esperança média de vida tem-se traduzido no envelhecimento progressivo da população mundial e consequente aumento da incidência de doenças associadas ao envelhecimento, tais como as doenças neurodegenerativas de Alzheimer ou de Parkinson. A doença de Parkinson é a segunda doença neurodegenerativa mais comum, a seguir à doença de Alzheimer, e é caracterizada pela degeneração progressiva de neurónios dopaminérgicos na substantia nigra pars compacta. Uma das características mais comuns desta doença é a formação de corpos de Lewy, estruturas maioritariamente compostas por a-sinucleína agregada. A perda dos neurónios dopaminérgicos conduz à redução da produção de dopamina, um neurotransmissor essencial à sinalização do movimento voluntário. Tal facto é responsável por várias manifestações motoras apresentadas pelos doentes. Estas incluem tremores, bradicinesia e rigidez muscular. Os doentes de Parkinson também podem manifestar sintomas não motores como a psicose, depressão, hiposmia e cognição comprometida. A maioria dos casos de Parkinson tem origem desconhecida, sendo o envelhecimento o seu maior fator de risco. A diabetes tem vindo a ser sugerida como um fator de risco importante para o aparecimento/desenvolvimento desta doença. Nomeadamente, cerca de 80% dos doentes de Parkinson apresentam intolerância à glucose; proteínas modificadas por açúcares nos seus cérebros; e falhas nas defesas contra os açucares. A hiperglicemia, consequência da diabetes, promove o aumento dos níveis de açúcares redutores no cérebro, tais como o metilglioxal. Este composto é um metabolito secundário, proveniente de diferentes vias metabólicas e, como outros açúcares redutores, pode reagir com proteínas numa reação denominada de glicação. A glicação é um processo que compreende uma série de reações entre açúcares redutores e grupos amina de proteínas, lípidos ou nucleótidos. Quando em reação com proteínas, formam como produto final os denominados produtos avançados de glicação (do inglês advanced glycation endproducts – AGEs). A glicação pode promover diversas alterações a diferentes níveis celulares, tais como disfunção mitocondrial, alteração de degradação proteica, ou até promoção de processos de inflamação. No contexto de modelos de Parkinson, verificou-se que a glicação induz o aumento da agregação e da toxicidade da a-sinucleína, provocando efeitos negativos em diversos processos celulares. Em
particular, a glicação da a-sinucleína induzida pelo metilglioxal, altera o seu clearance, e afeta o proteossoma, macro-autofagia e também a secreção, levando à sua acumulação. A glicação pelo metilglioxal conduz também à perda de neurónios dopaminérgicos na substantia nigra e no estriado em ratinhos, modelos da doença de Parkinson. Enquanto que a formação do metilglioxal é inevitável, este pode ser catabolizado por diferentes vias, sendo o sistema dos glioxalases um dos mais eficientes. Para além de processos enzimáticos, existem também compostos capazes de sequestrar metilglioxal e impedir que este reaja com as proteínas. Existem também compostos que inibem o processo de glicação, ou que têm capacidade de remover os AGEs das proteínas. Assim, coloca-se por hipótese que os compostos que previnam a glicação possam ser benéficos na prevenção ou tratamento da agregação e citotoxicidade da a-sinucleína. Tendo em conta que o metilglioxal assume um papel importante na doença de Parkinson, neste estudo foi avaliado o potencial terapêutico de diversos compostos supressores de glicação tais como a metformina, pioglitazona, sulforafane, resveratrol, carnosina e aminoguanidina. A atividade destes compostos foi avaliada pela sua capacidade em proteger dos efeitos deletérios induzidos pela glicação. Nomeadamente, em reduzir a citotoxicidade da a-sinucleína/metilglioxal; os níveis de a-sinucleína; a agregação de a-sinucleína; os níveis gerais de AGEs; bem como de potenciar o clearance de asinucleína. O potencial de proteção foi avaliado de forma preventiva (antes do insulto) ou restaurativa (após insulto com metilglioxal). Para este efeito, foi utilizado como modelo de estudo células H4 (neuroglioma) a sobre-expressar a-sinucleína. Os compostos a avaliar foram incubados na ausência e/ou presença metilglioxal. A citotoxicidade foi avaliada pela perda de integridade da membrana citoplasmática, medida pela actividade do enzima lactato desidrogenase libertado. Os níveis de asinucleína foram avaliados por Western blot. A solubilidade de proteínas em Triton X-100 permitiu estudar a solubilidade da a-sinucleína proveniente de um extrato nativo de células que expressam SynT, uma variante da a-sinucleína com maior tendência para agregar. Na presença deste detergente, as proteínas mais solúveis, após uma centrifugação a alta velocidade por um período longo de tempo, permanecem na fração solúvel, enquanto que as insolúveis ficam precipitadas na base do tubo de centrifugação (fração insolúvel). À fração insolúvel correspondem proteínas agregadas. A agregação da a-sinucleína foi também avaliada por imunocitoquímica. Ao hibridar a a-sinucleína com um anticorpo secundário fluorescente, é possível, recorrendo a um microscópio de fluorescência, visualizar a presença de agregados intracelulares. O “clearance” da a-sinucleína foi estudado pela monitorização dos níveis desta proteína por western blot, de extratos proteicos de células cuja síntese proteica de novo foi inibida (pelo uso de cicloheximida) em diferentes momentos no decurso do tempo. Os resultados obtidos neste estudo revelaram que a metformina, a carnosina e a aminoguanidina, nas concentrações testadas, não apresentam citotoxicidade num contexto basal. O mesmo se verifica quando as células expressam a a-sinucleína e/ou quando a glicação é induzida pelo metilglioxal. A metformina, a carnosina e a aminoguanidina apresentaram capacidade de reduzir a citotoxicidade induzida pelo metilglioxal em células que sobre-expressam a a-sinucleína. Tal verificou-se num contexto preventivo bem como restaurativo. A metformina e a carnosina são igualmente capazes de prevenir o aumento dos níveis gerais de AGEs e de a-sinucleína/SynT, induzido pelo metilglioxal. No entanto, o mesmo não foi observado num contexto restaurativo, onde apenas a carnosina reduziu os níveis de AGEs em células que expressam a variante SynT, e por isso num contexto em que a agregação da a-sinucleína está
potenciada. No que diz respeito ao perfil de solubilidade da a-sinucleína, a metformina solubilizou a proteína num contexto preventivo, o que sugere que tenha capacidade de prevenir a agregação da SynT. Por outro lado, a carnosina não parece modular a solubilidade da SynT. Num contexto restaurativo, nenhum dos compostos testados mostrou potencial para alterar a solubilidade da a-sinucleína. A agregação desta proteína foi também avaliada por imunocitoquímica. Uma vez que os compostos não apresentaram potencial restaurativo, a sua eficácia foi apenas avaliada num contexto preventivo. Os resultados preliminares revelam que tanto o tratamento com a metformina como com a carnosina resultam numa diminuição do número de células com agregados. Estes resultados estão em concordância com os observados nos testes de solubilidade. No que diz respeito ao clearance da a-sinucleína, os resultados preliminares sugerem que a metformina, não só previne contra os efeitos do metilglioxal (que
impede o clearance da a-sinucleína) como potencia o clearance da a-sinucleína. Em suma, os resultados obtidos neste estudo sugerem que a metformina e a carnosina apresentam elevado potencial de proteção contra a citotoxicidade da a-sinucleína (30% e 20%, respetivamente), principalmente num contexto de glicação. A sua eficácia é maior num contexto preventivo, em modelos que apresentam maior agregação da proteína, bem como em condições de glicação induzida pelo metilglioxal. Em contexto preventivo, tanto a metformina como a carnosina diminuem os níveis gerais de glicação, o que está em concordância com o facto destes compostos serem sequestradores de metilglioxal. A carnosina também apresentou capacidade de reduzir os níveis de a-sinucleína ou SynT em células glicadas com metilglioxal. Ainda num contexto preventivo, tanto a metformina como a carnosina preveniram a agregação da SynT. A metformina apresenta ainda potencial para aumentar o clearance da a-sinucleína. É importante referir que no que diz respeito aos estudos de agregação (imunocitoquímica), bem como os de clearance da a-sinucleína, os resultados apresentados nesta tese são preliminares, e carecem por isso de confirmação com experiências adicionais. De futuro, pretende-se ainda testar o efeito da carnosina no clearance da a-sinucleína. Com este estudo conclui-se que a metformina e a carnosina são compostos com elevado potencial de proteção/prevenção contra os efeitos citotóxicos da a-sinucleína, particularmente em condições de glicação induzida pelo metilglioxal. Sugere-se, por isso, que estes compostos são potenciais fármacos
para o tratamento da doença de Parkinson.Parkinson’s disease is the second most common neurodegenerative disorder, characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta, leading to several features of the disease such as abnormal motor performance and, at later stages, cognitive impairment. The main hallmark of this disease is the presence of Lewy bodies, which are primarily composed of a-synuclein. Diabetes has been associated as a risk factor for the development of Parkinson’s disease, and recently, glycation was suggested as the missing link between the two diseases. Reducing sugars, such as methylglyoxal, intervene in this reaction, leading to the formation of advance glycation end-products, which promote protein cross-linking. a-synuclein is an appealing target of glycation, since more than 10% of its residues are putative targets of this post-translational modification. Glycation is thought to play a key role in the aggregation of a-synuclein, as it promotes its aggregation and toxicity. As such, modulation of glycation defenses in Parkinson’s disease can represent a new therapeutic approach to delay or prevent the disease progression. This study aimed to evaluate the therapeutic potential of metformin, pioglitazone, sulforaphane, carnosine, and aminoguanidine, compounds already shown to protect against glycation toxic effects. To this purpose, the selected pharmacological compounds activity was tested, in a preventive or restorative paradigm, in cellular models of Parkinson’s disease under methylglyoxal-induced glycation. Regarding a-synuclein/methylglyoxal associated toxicity assessment, metformin and carnosine were the most active compounds. They were able to decrease toxicity both in a preventive and restorative manner. Moreover, these agents were also able to decrease the formation of advance glycation endproducts in cells treated with methylglyoxal. Carnosine, in a preventive manner, decreased a-synuclein protein levels. On the other hand, metformin is able to maintain a-synuclein (SynT) solubility. Preliminary data suggests that metformin not only decreases the number of cells with a-synuclein aggregates, but also promotes its clearance. In contrast, under a restorative paradigm, neither metformin nor carnosine modulate a-synuclein levels. In summary, metformin and carnosine have a protective potential against methylglyoxal-induced asynuclein glycation in a cellular model of Parkinson’s disease, making these a novel potential therapeutic approach to Parkinson’s disease
Qluster: An easy-to-implement generic workflow for robust clustering of health data
The exploration of heath data by clustering algorithms allows to better describe the populations of interest by seeking the sub-profiles that compose it. This therefore reinforces medical knowledge, whether it is about a disease or a targeted population in real life. Nevertheless, contrary to the so-called conventional biostatistical methods where numerous guidelines exist, the standardization of data science approaches in clinical research remains a little discussed subject. This results in a significant variability in the execution of data science projects, whether in terms of algorithms used, reliability and credibility of the designed approach. Taking the path of parsimonious and judicious choice of both algorithms and implementations at each stage, this article proposes Qluster, a practical workflow for performing clustering tasks. Indeed, this workflow makes a compromise between (1) genericity of applications (e.g. usable on small or big data, on continuous, categorical or mixed variables, on database of high-dimensionality or not), (2) ease of implementation (need for few packages, few algorithms, few parameters, ...), and (3) robustness (e.g. use of proven algorithms and robust packages, evaluation of the stability of clusters, management of noise and multicollinearity). This workflow can be easily automated and/or routinely applied on a wide range of clustering projects. It can be useful both for data scientists with little experience in the field to make data clustering easier and more robust, and for more experienced data scientists who are looking for a straightforward and reliable solution to routinely perform preliminary data mining. A synthesis of the literature on data clustering as well as the scientific rationale supporting the proposed workflow is also provided. Finally, a detailed application of the workflow on a concrete use case is provided, along with a practical discussion for data scientists. An implementation on the Dataiku platform is available upon request to the authors
Socioeconomic Impact Assessment of the Red Palm Weevil in NENA Countries (The Case of Egypt and Saudi Arabia) Ex-post impact assessment (impact evaluation of the proposed interventions)
Date palms are trees of high importance across the NENA region due to their economic and cultural importance, and also for their importance as a renewable natural resource and as a provider of other ecosystem services. Since its arrival in the NENA region, a main date palm production region, RPW is causing widespread damage to date palm and affecting date palm production, which is having a significant impact on the livelihoods of farmers as well as the environment
Identifying and responding to people with mild learning disabilities in the probation service
It has long been recognised that, like many other individuals, people with learningdisabilities find their way into the criminal justice system. This fact is not disputed. Whathas been disputed, however, is the extent to which those with learning disabilities arerepresented within the various agencies of the criminal justice system and the ways inwhich the criminal justice system (and society) should address this. Recently, social andlegislative confusion over the best way to deal with offenders with learning disabilities andmental health problems has meant that the waters have become even more muddied.Despite current government uncertainty concerning the best way to support offenders withlearning disabilities, the probation service is likely to continue to play a key role in thesupervision of such offenders. The three studies contained herein aim to clarify the extentto which those with learning disabilities are represented in the probation service, toexamine the effectiveness of probation for them and to explore some of the ways in whichprobation could be adapted to fit their needs.Study 1 and study 2 showed that around 10% of offenders on probation in Kent appearedto have an IQ below 75, putting them in the bottom 5% of the general population. Study 3was designed to assess some of the support needs of those with learning disabilities in theprobation service, finding that many of the materials used by the probation service arelikely to be too complex for those with learning disabilities to use effectively. To addressthis, a model for service provision is tentatively suggested. This is based on the findings ofthe three studies and a pragmatic assessment of what the probation service is likely to becapable of achieving in the near future
Gamma-rays in low-background facilities:fundamentals of spectra measurement and energy calibration at Callio Lab
Abstract. Low-background gamma spectroscopy is an essential tool in designing and building low- and ultra-low-background experiments. Low-background experiments study extremely rare phenomena, where a detector may expect to see one signal a day. The experiment must be designed and constructed so that the true signals can be separated from the background. The background consists of three sources: cosmic-ray-induced, environmental, and instrumental radiation.
The background from cosmic-rays can be mitigated by situating the experiment deeper underground and by using veto detectors. The natural background radiation can be mitigated by choosing the appropriate location according to preliminary NBR characterisation and taking the necessary steps to shield the detector from the remaining radioactivity. The third, and perhaps most challenging, source of background is the gamma-ray background from the radioactivity of the detector instrumentation and shielding itself.
Gamma-rays are high-energy electromagnetic radiation that carry energy in discrete units called photons. Gamma-rays interact through the photoelectric effect, Compton scattering, and pair production within the detector and detector shielding. These interactions create the signature gamma-ray peaks and other gamma spectrum features, which allow the identification of radionuclides present in the measurement chamber. Radionuclides produce gamma-rays of various energies, which have been well-documented and can be used as references. Of the three most common types of gamma detectors (gas-filled, scintillation, and semiconductor detectors), semiconductor germanium-based HPGe detectors are the most suited for low-background radionuclide analysis due to their usability and good resolution.
Low-background experiments are situated in deep underground laboratories because the overburden effectively shields from the cosmic-ray flux. One potential reuse application for underground facilities is in the field of low-background experiments. Such facilities already exist at, for example, the HADES and Felsenkeller underground laboratories. SNOLAB was developed as a dedicated low-background facility to support the activities at the Sudbury Neutrino Observatory. Low-background gamma spectra measurements can require weeks or months to complete, so more DULs with material assaying capabilities are needed.
The possibility of using Callio Lab at the Pyhäsalmi Mine in Finland as a site for low-background gamma activities was piloted and evaluated during the BSUIN project, providing extensive characterisation of the natural background environment. Low-background gamma spectroscopy was practiced in Lab 2 and Lab 5 at Callio Lab. A dedicated gamma spectrometer setup was used for the characterisation of natural background radiation and for low-background materials sample measurement. This provided practice on the transport, start-up, calibration, and operation of a HPGe spectrometer setup. Lab 5 was deemed a viable location for further low-background activities in regard to usability, characterisation, and trained personnel familiar with gamma spectrometry.
The HPGe spectrometer was recalibrated after transport from Lab 2 to Lab 5. Preliminary calibrations included energy and full-width half maximum calibrations with dedicated software SpectraLine. For the purposes of becoming familiar with the use of the gamma spectrometer and evaluating possible experiment changes, these primary calibrations were sufficient. Preliminary comparison of acquired spectra of background and the high-purity samples showed that the background present was as high or higher than the sample. The HPGe instrument used is defined as a low-background device fitted with standard industrial shielding. In practice, the limitations of this setup and shielding were reached with the measurement of high-purity samples. The current limits are defined by the radioactive background, and further study should be conducted to ascertain whether it is of environmental or instrumental origin.
An understanding of gamma-ray sources and interactions is essential for the evaluation and development of better low-background gamma spectrometry setups. Before focusing on the instrument background, which should be low already due to the use of radiopurity-certified materials, other aspects should be considered. Further study and development of the experiment setup will improve the low-background measurement capabilities at Callio Lab to an even higher-level
The Cerebral Plasticity Prospect of Stingless Bee Honey-Polyphenols Supplementation in Rehabilitation of Post-Stroke Vascular Cognitive Impairment
The neuroprotective potential of stingless bee honey (SBH) is still to be documented from numerous studies including that of its effect on cerebrovascular event. This review should guide stroke rehabilitation specialties to a high understanding of the overall circuit changes post-stroke, the clinical relevance of this change in stroke to cognitive impairment and dementia, and SBH as a supplementation in modern stroke rehabilitation in progresses. However, the potential of SBH as a supplementation therapy and highlights treatment to induced plasticity for post-stroke vascular cognitive impairment (PSVCI) remains largely unexplored. This Chapter attempts to deliberate on recent evidence that highlight the therapeutic properties of honey and SBH, the features of PSVCI, and proposing the plausible mechanism of action for SBH as a supplementation during stroke rehabilitation that could halt the progression of PSVCI. It is hoped that such an approach could complement the existing evidence-based stroke care, and which will help in the development of future direction of brain plasticity to delay the progression of cognitive impairment post-stroke
The Role of the Metabolome in the Development of Gestational Diabetes Mellitus in High-Risk Minority Women: A Causal Investigation
Gestational Diabetes Mellitus (GDM) is the most common pregnancy complication worldwide. However, GDM prevalence is substantially lower in white Europeans (WEs) compared to other ethnicities, especially South Asians (SAs) who experience the highest risk. Globally, healthy diet promotion is the mainstay in GDM prevention, however current guidelines are predominantly based on evidence from WEs. Furthermore, metabolic factors responsible for the disparities in prevalence are unknown but may offer guidance for improved prevention and management.
This project aimed to (i) assess the association between diet and GDM across ethnic groups, (ii) determine if distinct metabolic profiles characterise GDM in SAs and WEs, and (iii) evaluate the presence of ethnic-specific causal associations between metabolites and gestational dysglycemia. Aims (ii) and (iii) utilised data from the Born in Bradford cohort (mean gestational age 26.1 weeks).
First, through a systematic review of observational and randomised studies, pre-pregnancy diet was found to associate with GDM in WEs, but not in Asians. Secondly, the multivariate analyses of metabolites identified 7 metabolites that were characteristic of GDM in both ethnicities, with an additional 6 characteristic in WEs only. Finally, through Mendelian Randomisation (MR) analyses, 14 metabolites associated with pregnancy dysglycemia in WEs and 11 in SAs. No metabolites were identified in both ethnicities. Cholesterols and fatty acids were the most commonly identified classes identified in WEs and SAs, respectively.
This project demonstrated (i) inconsistencies in the association between diet and GDM across ethnicities (ii) distinct metabolic profiles that associate with GDM in WEs and SAs and offers and supports the need for ethnic-specific manage GDM management strategies. In high-risk SAs, fatty acids may be the most important predictors of GDM. Future work should evaluate the role of pre-pregnancy fatty acid intake in GDM development in SAs to aid in the development of culturally tailored dietary interventions
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