643 research outputs found

    Monetary Policy and Stock Market Booms

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    Historical data and model simulations support the following conclusion. Inflation is low during stock market booms, so that an interest rate rule that is too narrowly focused on inflation destabilizes asset markets and the broader economy. Adjustments to the interest rate rule can remove this source of welfare-reducing instability. For example, allowing an independent role for credit growth (beyond its role in constructing the inflation forecast) would reduce the volatility of output and asset prices.

    Association of clusterin with the BRI2-derived amyloid molecules ABri and ADan

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    Familial British and Danish dementias (FBD and FDD) share striking neuropathological similarities with Alzheimer's disease (AD), including intraneuronal neurofibrillary tangles as well as parenchymal and vascular amyloid deposits. Multiple amyloid associated proteins with still controversial role in amyloidogenesis colocalize with the structurally different amyloid peptides ABri in FBD, ADan in FDD, and Aβ in AD. Genetic variants and plasma levels of one of these associated proteins, clusterin, have been identified as risk factors for AD. Clusterin is known to bind soluble Aβ in biological fluids, facilitate its brain clearance, and prevent its aggregation. The current work identifies clusterin as the major ABri- and ADan-binding protein and provides insight into the biochemical mechanisms leading to the association of clusterin with ABri and ADan deposits. Mirroring findings in AD, the studies corroborate clusterin co-localization with cerebral parenchymal and vascular amyloid deposits in both disorders. Ligand affinity chromatography with downstream Western blot and amino acid sequence analyses unequivocally identified clusterin as the major ABri- and ADan-binding plasma protein. ELISA highlighted a specific saturable binding of clusterin to ABri and ADan with low nanomolar Kd values within the same range as those previously demonstrated for the clusterin-Aβ interaction. Consistent with its chaperone activity, thioflavin T binding assays clearly showed a modulatory effect of clusterin on ABri and ADan aggregation/fibrillization properties. Our findings, together with the known multifunctional activity of clusterin and its modulatory activity on the complex cellular pathways leading to oxidative stress, mitochondrial dysfunction, and the induction of cell death mechanisms - all known pathogenic features of these protein folding disorders - suggests the likelihood of a more complex role and a translational potential for the apolipoprotein in the amelioration/prevention of these pathogenic mechanisms.This work was supported by grants from the National Institutes of Health NS051715 (to AR) and AG030539, AG051266, AG059695, and AG065651 (to JG) and from CIBERNED and the Spanish Ministry of Science (SAF2016-78603-R and PID2019-110401RB-I00) and Institutional grants from the Queen Sofia Foundation, CIEN Foundation and the Carlos III Institutes of Health (to MC). TL is supported by an Alzheimer's Research UK senior fellowship. TR is supported by a grant from the Karin & Sten Mortstedt CBD Solutions AB, Stockholm, Sweden and by the National Institute for Health Research (NIHR) Queen Square Biomedical Research Unit in Dementia based at University College London Hospitals (UCLH), University College London (UCL). The views expressed are those of the authors and not necessarily those of the NIH, NHS, the NIHR or the Department of Health.S

    MEDEA: A Hybrid Shared-memory/Message-passing Multiprocessor NoC-based Architecture

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    The shared-memory model has been adopted, both for data exchange as well as synchronization using semaphores in almost every on-chip multiprocessor implementation, ranging from general purpose chip multiprocessors (CMPs) to domain specific multi-core graphics processing units (GPUs). Low-latency synchronization is desirable but is hard to achieve in practice due to the memory hierarchy. On the contrary, an explicit exchange of synchronization tokens among the processing elements through dedicated on-chip links would be beneficial for the overall system performance. In this paper we propose the Medea NoC-based framework, a hybrid shared-memory/message-passing approach. Medea has been modeled with a fast, cycle-accurate SystemC implementation enabling a fast system exploration varying several parameters like number and types of cores, cache size and policy and NoC features. In addition, every SystemC block has its RTL counterpart for physical implementation on FPGAs and ASICs. A parallel version of the Jacobi algorithm has been used as a test application to validate the metodology. Results confirm expectations about performance and effectiveness of system exploration and design

    An Open Source Quantitative Evaluation Framework for Automatic Video Summarization Algorithms

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    The creation, consumption, and manipulation of video play a central role in everyday life as the amount of video data is growing at an exponential rate. Video summarization consists on producing a condensed output from a video that allows humans to rapidly understand and browse the content of the original source. Although there are several evaluation approaches proposed in the literature, multiple challenges make the quantitative evaluation of a summarization a complex process. In this paper we present a completely open video summarization evaluation framework that is compatible with existing datasets and published results. Standard metrics are considered and a new metric that captures unbalanced-class video summarization evaluation is proposed. Two legacy datasets are integrated in a standard format. Finally, new quantitative results based on already published algorithms are presented.Sociedad Argentina de Informática e Investigación Operativ

    Ternary combination of irinotecan, fluorouracil-folinic acid and oxaliplatin: results on human colon cancer cell lines

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    A marked antitumour efficacy is currently obtained by oxaliplatin (LOHP)–fluorouracil (FU)–folinic acid (FA) combination and by CPT11–FU–FA combination. Logically, the triple association LOHP, CPT11 and FUFA will be soon tested in cancer patients. The aim of the present study was to compare two schedules combining SN38 (the active metabolite of CPT11, irinotecan) with FU–FA and LOHP. The two schedules differed by the SN38 position. The relative contribution of each drug in the resulting global cytotoxicity was evaluated. Two human colon cancer cell lines were used (WIDR and SW620 both p53 mutated). LOHP plus FA were applied for 2 h, just before a 48 h FU exposure. The SN38 sequence was applied for 24 h, starting either 48 h before LOHP-FA (schedule A), or just after LOHP-FA exposure (schedule B). Cytotoxicity was assessed by the 3-(4,5-demethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) test and drug interactions were analysed according to the Chou and Talalay method, based on the computation of a combination index (CI). The SN38 position significantly induces a shift from additivity-antagonism when SN38 was applied after LOHP, towards additivity-synergism when SN38 was applied first (P = 0.03). The relative contribution (RC) of each drug in the overall cytotoxicity of the triple combination was defined as the drug concentration giving 50% cell lethality (IC 50) of the double association without that drug divided by the IC 50 of the triple association. Whatever the SN38 position, the larger contribution was made by LOHP (median RC = 2.4) and the smaller by SN38 (median RC = 1.1). In addition, the contribution of FUFA was improved when SN38 was applied first (median RC = 2.2) as compared to the opposite schedule (median RC = 1.2). Results were in agreement between the two explored cell lines. The present data should be taken into account when establishing the rationale of future trials combining CPT11, LOHP and FU–FA. © 2001 Cancer Research Campaign http://www.bjcancer.co

    An Open Source Quantitative Evaluation Framework for Automatic Video Summarization Algorithms

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    The creation, consumption, and manipulation of video play a central role in everyday life as the amount of video data is growing at an exponential rate. Video summarization consists on producing a condensed output from a video that allows humans to rapidly understand and browse the content of the original source. Although there are several evaluation approaches proposed in the literature, multiple challenges make the quantitative evaluation of a summarization a complex process. In this paper we present a completely open video summarization evaluation framework that is compatible with existing datasets and published results. Standard metrics are considered and a new metric that captures unbalanced-class video summarization evaluation is proposed. Two legacy datasets are integrated in a standard format. Finally, new quantitative results based on already published algorithms are presented.Sociedad Argentina de Informática e Investigación Operativ
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