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31.
Multiple-system trophy (MSA) and Parkinson’s Disease (PD) are both progressive, neurodegenerative diseases characterized by neuropathological deposition of aggregated alpha-synuclein (αSyn). The causes behind this aggregation are still unknown. We have reported aberrancies in MSA and PD patients in naturally occurring autoantibodies (nAbs) against αSyn (anti-αSyn-nAbs), which are important partakers in anti-aggregatory processes, immune-mediated clearance, and anti-inflammatory functions. To elaborate further on the timeline of autoimmune aberrancies towards αSyn, we investigated here the Immunoglobulin (Ig) affinity profile and subclass composition (IgG-total, IgG1-4 and IgM) of anti-αSyn-nAbs in serum samples from prodromal (p) phases of MSA and PD. Using an electrochemiluminescence competition immunoassay, we confirmed that the repertoire of high-affinity anti-αSyn-nAbs is significantly reduced in pMSA and pPD. Further, we demonstrated that pPD had increased anti-αSyn IgG-total levels compared to pMSA and controls, concordant with increased anti-αSyn IgG1 levels in pPD. Anti-αSyn IgG2 and IgG4 levels were reduced in pMSA and pPD compared with controls, whereas anti-αSyn IgG3 levels were reduced in pMSA compared to pPD and controls. The results indicate that the impaired reactivity towards αSyn occurs prior to disease onset. The apparent lack of high-affinity anti-αSyn nAbs may result in reduced clearance of αSyn, leading to aggregation of the protein. Thus, this study provides novel insights into possible causes behind the pathogenesis in synucleinopathies such as MSA and PD.  相似文献   
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Molecular dynamics simulations are used to investigate the behavior of polymer-tethered nanoparticles between two inert or attractive walls. The confinement in pores creates new possibilities for controlling the shape transformation of individual hairy particles and their self-organization. We introduce a minimalistic model of the system; only chain-wall interactions are assumed to be attractive, while the others are softly repulsive. We show how the shape of isolated particles can be controlled by changing the wall separation and the strength of the interaction with the surfaces. For attractive walls, we found two types of structures, “bridges” and “mounds”. The first structures are similar to flanged spools in which the chains are connected with both walls and form bridges between them. We observed various bridges, symmetrical and asymmetrical spools, hourglasses, and pillars. The bridge-like structures can be “nano-oscillators” in which the cores jump from one wall to the other. We also study the self-assembly of a dense fluid of hairy particles in slit-like pores and analyze how the system morphology depends on interactions with the surfaces and the wall separation. The hairy particles form layers parallel to the walls. Different ordered structures, resembling two-dimensional crystalline lattices, are reported. We demonstrate that hairy particles are a versatile soft component forming a variety of structures in the slits.  相似文献   
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We present an overview of some recent developments in the area of mathematical modeling of maintenance decisions for multi-unit systems. The emphasis is on three main groups of multicomponent maintenance optimization models: the block replacement models, group maintenance models, and opportunistic maintenance models. Moreover, an example of a two-unit system maintenance process is provided in order to compare various maintenance policies.  相似文献   
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The technique of Hotspot Mapping is widely used in analysing the spatial characteristics of crimes. The spatial distribution of crime is considered to be related with a variety of socio-economic and crime opportunity factors. But existing methods usually focus on the target crime density as input without utilizing these related factors. In this study, we introduce a new crime hotspot mapping tool—Hotspot Optimization Tool (HOT). HOT is an application of spatial data miming to the field of hotspot mapping. The key component of HOT is the Geospatial Discriminative Patterns (GDPatterns) concept, which can capture the differences between two classes in a spatial dataset. Experiments are done using a real world dataset from a northeastern city in the United States and the pros and cons of utilizing related factors in hotspot mapping are discussed. Comparison studies with the Hot Spot Analysis tool implemented by Esri ArcMap 10.1 validate that HOT is capable of accurately mapping crime hotspots.  相似文献   
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The present work compares the states of the surface textures and the oscillatory fatigue strengths of specimens made of an AZ91 alloy after turning and dynamic bearing ball peening. It was found that the specimens ball peened at different time have similar surface geometric structure parameters but different strengthening intensity. It was shown that fatigue strength follows greater peening intensity and random and isotropic surface. It was also ascertained that improving (by peening) the condition of the surface layer means enhancing fatigue strength by 20–87% compared with turning.  相似文献   
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Field programmable gate array (FPGA) is a flexible solution for offloading part of the computations from a processor. In particular, it can be used to accelerate an execution of a computationally heavy part of the software application, e.g., in DSP, where small kernels are repeated often. Since an application code for a processor is a software, a design methodology is needed to convert the code into a hardware implementation, applicable to the FPGA. In this paper, we propose a design method, which uses the Transport Triggered Architecture (TTA) processor template and the TTA-based Co-design Environment toolset to automate the design process. With software as a starting point, we generate a RTL implementation of an application-specific TTA processor together with the hardware/software interfaces required to offload computations from the system main processor. To exemplify how the integration of the customized TTA with a new platform could look like, we describe a process of developing required interfaces from a scratch. Finally, we present how to take advantage of the scalability of the TTA processor to target platform and application-specific requirements.  相似文献   
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