2,265 research outputs found

    Nonlinear stochastic receding horizon control: stability, robustness and Monte Carlo methods for control approximation

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    © 2017, © 2017 Informa UK Limited, trading as Taylor & Francis Group. This work considers the stability of nonlinear stochastic receding horizon control when the optimal controller is only computed approximately. A number of general classes of controller approximation error are analysed including deterministic and probabilistic errors and even controller sample and hold errors. In each case, it is shown that the controller approximation errors do not accumulate (even over an infinite time frame) and the process converges exponentially fast to a small neighbourhood of the origin. In addition to this analysis, an approximation method for receding horizon optimal control is proposed based on Monte Carlo simulation. This method is derived via the Feynman–Kac formula which gives a stochastic interpretation for the solution of a Hamilton–Jacobi–Bellman equation associated with the true optimal controller. It is shown, and it is a prime motivation for this study, that this particular controller approximation method practically stabilises the underlying nonlinear process

    Thermal stability and aggregation of sulfolobus solfataricus b-glycosidase are dependent upon the N-e-methylation of specific lysyl residues: critical role of in vivo post-translational modifications.

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    Methylation in vivo is a post-translational modification observed in several organisms belonging to eucarya, bacteria, and archaea. Although important implications of this modification have been demonstrated in several eucaryotes, its biological role in hyperthermophilic archaea is far from being understood. The aim of this work is to clarify some effects of methylation on the properties of ÎČ-glycosidase from Sulfolobus solfataricus, by a structural comparison between the native, methylated protein and its unmethylated counterpart, recombinantly expressed in Escherichia coli. Analysis by Fourier transform infrared spectroscopy indicated similar secondary structure contents for the two forms of the protein. However, the study of temperature perturbation by Fourier transform infrared spectroscopy and turbidimetry evidenced denaturation and aggregation events more pronounced in recombinant than in native ÎČ-glycosidase. Red Nile fluorescence analysis revealed significant differences of surface hydrophobicity between the two forms of the protein. Unlike the native enzyme, which dissociated into SDS-resistant dimers upon exposure to the detergent, the recombinant enzyme partially dissociated into monomers. By electrospray mapping, the methylation sites of the native protein were identified. A computational analysis of ÎČ-glycosidase three-dimensional structure and comparisons with other proteins from S. solfataricus revealed analogies in the localization of methylation sites in terms of secondary structural elements and overall topology. These observations suggest a role for the methylation of lysyl residues, located in selected domains, in the thermal stabilization of ÎČ-glycosidase from S. solfataricu

    The effect of a secondary task on kinematics during turning in Parkinson's disease with mild to moderate impairment

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    Patients with Parkinson's disease (PD) show typical gait asymmetries. These peculiar motor impairments are exacerbated by added cognitive and/or mechanical loading. However, there is scarce literature that chains these two stimuli. The aim of this study was to investigate the combined effects of a dual task (cognitive task) and turning (mechanical task) on the spatiotemporal parameters in mild to moderate PD. Participants (nine patients with PD and nine controls (CRs)) were evaluated while walking at their self-selected pace without a secondary task (single task), and while repeating the days of the week backwards (dual task) along a straight direction and a 60 degrees and 120 degrees turn. As speculated, in single tasking, PD patients preferred to walk with a shorter stride length (p< 0.05) but similar timing parameters, compared to the CR group; in dual tasking, both groups walked slower with shorter strides. As the turn angle increased, the speed will be reduced (p< 0.001), whereas the ground-foot contact will become greater (p< 0.001) in all the participants. We showed that the combination of a simple cognitive task and a mechanical task (especially at larger angles) could represent an important training stimulus in PD at the early stages of the pathology

    In silico approach for the definition of radiomirnomic signatures for breast cancer differential diagnosis

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    Personalized medicine relies on the integration and consideration of specific characteristics of the patient, such as tumor phenotypic and genotypic profiling. BACKGROUND: Radiogenomics aim to integrate phenotypes from tumor imaging data with genomic data to discover genetic mechanisms underlying tumor development and phenotype. METHODS: We describe a computational approach that correlates phenotype from magnetic resonance imaging (MRI) of breast cancer (BC) lesions with microRNAs (miRNAs), mRNAs, and regulatory networks, developing a radiomiRNomic map. We validated our approach to the relationships between MRI and miRNA expression data derived from BC patients. We obtained 16 radiomic features quantifying the tumor phenotype. We integrated the features with miRNAs regulating a network of pathways specific for a distinct BC subtype. RESULTS: We found six miRNAs correlated with imaging features in Luminal A (miR-1537, -205, -335, -337, -452, and -99a), seven miRNAs (miR-142, -155, -190, -190b, -1910, -3617, and -429) in HER2+, and two miRNAs (miR-135b and -365-2) in Basal subtype. We demonstrate that the combination of correlated miRNAs and imaging features have better classification power of Luminal A versus the different BC subtypes than using miRNAs or imaging alone. CONCLUSION: Our computational approach could be used to identify new radiomiRNomic profiles of multi-omics biomarkers for BC differential diagnosis and prognosis

    Upscaling of a dual-permeability Monte Carlo simulation model for contaminant transport in fractured networks by genetic algorithm parameter identification

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    International audienceThe transport of radionuclides in fractured media plays a fundamental role in determining the level of risk offered by a radioactive waste repository in terms of expected doses. Discrete Fracture Networks (DFN) methods can provide detailed solutions to the problem of modeling the contaminant transport in fractured media. However, within the framework of the performance assessment (PA) of radioactive waste repositories, the computational efforts required are not compatible with the repeated calculations that need to be performed for the probabilistic uncertainty and sensitivity analyses of PA. In this paper, we present a novel upscaling approach, which consists in computing the detailed numerical fractured flow and transport solutions on a small scale and use the results to derive the equivalent continuum parameters of a lean, one-dimensional Dual-Permeability, Monte Carlo Simulation (DPMCS) model by means of a Genetic Algorithm search. The proposed upscaling procedure is illustrated with reference to a realistic case study of migration taken from literature

    D-SPACE4Cloud: A Design Tool for Big Data Applications

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    The last years have seen a steep rise in data generation worldwide, with the development and widespread adoption of several software projects targeting the Big Data paradigm. Many companies currently engage in Big Data analytics as part of their core business activities, nonetheless there are no tools and techniques to support the design of the underlying hardware configuration backing such systems. In particular, the focus in this report is set on Cloud deployed clusters, which represent a cost-effective alternative to on premises installations. We propose a novel tool implementing a battery of optimization and prediction techniques integrated so as to efficiently assess several alternative resource configurations, in order to determine the minimum cost cluster deployment satisfying QoS constraints. Further, the experimental campaign conducted on real systems shows the validity and relevance of the proposed method

    Theranostic application of miR-429 in HER2+ breast cancer

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    Human epidermal growth factor receptor 2 (HER2) is overexpressed/amplified in one third of breast cancers (BCs), and is associated with the poorer prognosis and the higher metastatic potential in BC. Emerging evidences highlight the role of microRNAs (miRNAs) in the regulation of several cellular processes, including BC. Methods: Here we identified, by in silico approach, a group of three miRNAs with central biological role (high degree centrality) in HER2+ BC. We validated their dysregulation in HER2+ BC and we analysed their functional role by in vitro approaches on selected cell lines and by in vivo experiments in an animal model. Results: We found that their expression is dysregulated in both HER2+ BC cell lines and human samples. Focusing our study on the only upregulated miRNA, miR-429, we discovered that it acts as an oncogene and its upregulation is required for HER2+ cell proliferation. It controls the metastatic potential of HER2+ BC subtype by regulating migration and invasion of the cell. Conclusions: In HER2+ BC oncogenic miR-429 is able to regulate HIF1\u3b1 pathway by directly targeting VHL mRNA, a molecule important for the degradation of HIF1\u3b1. The overexpression of miR-429, observed in HER2+ BC, causes increased proliferation and migration of the BC cells. More important, silencing miR-429 succeeds in delaying tumor growth, thus miR-429 could be proposed as a therapeutic probe in HER2+ BC tumors

    Biology and distribution of Danube barbel (Barbus balcanicus) (Osteichthyes: Cyprinidae) at the Northwestern limit of its range

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    Presence of Danube barbel Barbus balcanicus was investigated at the westernmost portion of its distribution area (Italian portion of the Isonzo River Basin). Genetic analyses carried out on specimens collected in different watercourses confirmed B. balcanicus presence in the same locations where Barbus caninus was erroneously classified in the past. More precisely, 4 Cyt b haplotypes belonging to the Balkanic species were described, three of which were evidenced for the first time. Analysis of meristic characters also confirmed genetic results and completed the taxonomical assessment. At the same time, a target population was studied to deepen knowledge about the species ecology. In this case, 120 specimens belonging to five age classes (from 0+ to 4+) were collected with monthly frequency in Barbucina Creek, representing the model watercourse inhabited by the species in the study area. Regression between total weight (W) and standard length (SL) did not differ significantly between males and females, therefore not displaying sexual dimorphism. SL values showed wide ranges, often overlapping among age classes. Mean condition factor (Kmean) decreased significantly with growth and age, as small individuals were in better nutritional condition. From an ecological point of view, biometric parameters seemed to be affected by habitat conditions and, specifically, to the limited space of the creeks, rather than by trophic conditions. Finally, trends of gonadosomatic index (GSI) showed that B. balcanicus reproductive period stretches between April and late May/early June. Results indicated that sexual maturity is reached at 1+ age, corresponding to a mean standard length equal to 5.50 ± 0.66 for female and 5.71 ± 0.53 for male breeders. In conclusion, experimental results highlighted the presence and adaptability of this "forgotten" species of the Italian fish fauna, which certainly will deserve attention in a future amendment of the Italian IUCN Red List of vertebrates

    Als‐associated sod1(G93a) decreases serca pump levels and increases store‐operated ca2+ entry in primary spinal cord astrocytes from a transgenic mouse model

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    Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by the selective death of motor neurons (MNs), probably by a combination of cell- and non-cell-autonomous processes. The past decades have brought many important insights into the role of astrocytes in nervous system function and disease, including the implication in ALS pathogenesis possibly through the impairment of Ca2+-dependent astrocyte-MN cross-talk. In this respect, it has been recently proposed that altered astrocytic store-operated Ca2+ entry (SOCE) may underlie aberrant gliotransmitter release and astrocyte-mediated neurotoxicity in ALS. These observations prompted us to a thorough investigation of SOCE in primary astrocytes from the spinal cord of the SOD1(G93A) ALS mouse model in comparison with the SOD1(WT)-expressing controls. To this purpose, we employed, for the first time in the field, genetically-encoded Ca2+ indicators, allowing the direct assessment of Ca2+ fluctuations in different cell domains. We found increased SOCE, associated with decreased expression of the sarco-endoplasmic reticulum Ca2+-ATPase and lower ER resting Ca2+ concentration in SOD1(G93A) astrocytes compared to control cells. Such findings add novel insights into the involvement of astrocytes in ALS MN damage

    External Validation Of Equations To Estimate Resting Energy Expenditure In 14952 Adults With Overweight And Obesity And 1948 Adults With Normal Weight From Italy

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    Background & aims: We cross-validated 28 equations to estimate resting energy expenditure (REE) in a very large sample of adults with overweight or obesity. Methods: 14952 Caucasian men and women with overweight or obesity and 1498 with normal weight were studied. REE was measured using indirect calorimetry and estimated using two meta-regression equations and 26 other equations. The correct classification fraction (CCF) was defined as the fraction of subjects whose estimated REE was within 10% of measured REE. Results: The highest CCF was 79%, 80%, 72%, 64%, and 63% in subjects with normal weight, overweight, class 1 obesity, class 2 obesity, and class 3 obesity, respectively. The Henry weight and height and Mifflin equations performed equally well with CCFs of 77% vs. 77% for subjects with normal weight, 80% vs. 80% for those with overweight, 72% vs. 72% for those with class 1 obesity, 64% vs. 63% for those with class 2 obesity, and 61% vs. 60% for those with class 3 obesity. The Sabounchi meta-regression equations offered an improvement over the above equations only for class 3 obesity (63%). Conclusions: The accuracy of REE equations decreases with increasing values of body mass index. The Henry weight & height and Mifflin equations are similarly accurate and the Sabounchi equations offer an improvement only in subjects with class 3 obesity
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