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1.
Software and Systems Modeling - Mobile robots operate in various environments (e.g. aquatic, aerial, or terrestrial), they come in many diverse shapes and they are increasingly becoming parts of...  相似文献   
2.
Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions.  相似文献   
3.
Extracellular vesicles (EVs) are a heterogeneous group of cell-derived submicron vesicles released under physiological or pathological conditions. EVs mediate the cellular crosstalk, thus contributing to defining the tumor microenvironment, including in epithelial ovarian cancer (EOC). The available literature investigating the role of EVs in EOC has been reviewed following PRISMA guidelines, focusing on the role of EVs in early disease diagnosis, metastatic spread, and the development of chemoresistance in EOC. Data were identified from searches of Medline, Current Contents, PubMed, and from references in relevant articles from 2010 to 1 April 2020. The research yielded 194 results. Of these, a total of 36 papers, 9 reviews, and 27 original types of research were retained and analyzed. The literature findings demonstrate that a panel of EV-derived circulating miRNAs may be useful for early diagnosis of EOC. Furthermore, it appears clear that EVs are involved in mediating two crucial processes for metastatic and chemoresistance development: the epithelial–mesenchymal transition, and tumor escape from the immune system response. Further studies, more focused on in vivo evidence, are urgently needed to clarify the role of EV assessment in the clinical management of EOC patients.  相似文献   
4.
Low-frequency noise measurements represent an interesting investigation technique for the characterization of the quality and reliability of microelectronic materials and devices. Performing meaningful noise measurements at low and very low (f<1 Hz) frequencies, however, may be quite challenging, particularly because of the many sources of interference that superimpose on the noise signal. For this reason, packaged samples are preferred because they allow accurate shielding from the external environment, and because keeping the sample in close proximity to the low-noise biasing system and amplifier reduces microphonic and electromagnetic disturbances. Notwithstanding this, the possibility of performing low-frequency noise measurements at wafer level would be quite interesting, both because of the ease of obtaining wafer-level samples from industries with respect to packaged samples, and because this would avoid possible packaging-process induced device degradation. The purpose of this work is to demonstrate that it is, in fact, possible to design and build a dedicated probe system for performing high-sensitivity, low-frequency noise measurements on metal-oxide-semiconductor devices at wafer level.  相似文献   
5.
The development of autonomous mobile machines to perform useful tasks in real work environments is currently being impeded by concerns over effectiveness, commercial viability and, above all, safety. This paper introduces a case study of a robotic excavator to explore a series of issues around system development, navigation in unstructured environments, autonomous decision making and changing the behaviour of autonomous machines to suit the prevailing demands of users. The adoption of the Real-Time Control Systems (RCS) architecture (Albus, 1991) is proposed as a universal framework for the development of intelligent systems. In addition it is explained how the use of Partially Observable Markov Decision Processes (POMDP) (Kaelbling et al., 1998) can form the basis of decision making in the face of uncertainty and how the technique can be effectively incorporated into the RCS architecture. Particular emphasis is placed on ensuring that the resulting behaviour is both task effective and adequately safe, and it is recognised that these two objectives may be in opposition and that the desired relative balance between them may change. The concept of an autonomous system having “values” is introduced through the use of utility theory. Limited simulation results of experiments are reported which demonstrate that these techniques can create intelligent systems capable of modifying their behaviour to exhibit either ‘safety conscious’ or ‘task achieving’ personalities.  相似文献   
6.
Aside from the economic factors that make biosensors attractive, on-board signal conditioning and signal processing improve the limits of detection and simplify use of the devices. The present discussion summarizes the breadth of biosensor design and application, and the requirements of clinical assay detection. Current sensor research is aimed toward extending the lower limits of detection for nonradioactive immunoassays. The clinical laboratory is in a state of change; operating and instrumentation costs will affect the delivery of diagnostics. Technology will assume a major role in reshaping the clinical laboratory. Biosensors promise to deliver the diagnostic tools for the evolution that is now in progress. The clinical laboratory will no doubt continue to perform chemical profiling and the more specialized tests. The successful implementation of solid-state sensor technology promises to simplify immunoassay procedures, as the autoanalyzer did some 20 years ago for the profiling of blood metabolites. It is likely that more tests will be performed in physicians' offices with the advent of highly automated and cost-effective biosensors. By the use of this technology, practitioners of critical care medicine will be able to assume greater responsibility for diagnostic testing.  相似文献   
7.
The ab-initio crystal structure solution by powder diffraction data requires great efforts because of the collapse of the experimental information onto the one dimensional 2θ axis of the pattern. Different strategies will be described aiming at improving the process of extraction of the integrated intensities from the experimental pattern in order to make more straightforward the structure solution process by direct methods. Particular attention will be devoted to the EXPO program. Some of its performance will be analysed and results will be shown.  相似文献   
8.
The deployment of highly powerful and sophisticated new-generation satellite broadband systems implies that a large portion of their bandwidth on the radio interface has to be devoted to conveying signalling information. Adequately dimensioning such a signalling bandwidth is an important design objective allowing the effective exploitation of the overall system resources and the cost-effective provision of a target quality of service to multimedia traffic. The performance of two basic techniques for accessing the signalling channels in a reference multimedia geostationary platform is investigated in this paper: random (slotted Aloha) and dedicated access. It is demonstrated here that dedicated access, despite rational appearances, allows 50% saving of signalling bandwidth while satisfying both the system and user constraints in terms of grade and quality of service respectively. This is accomplished by providing a statistical centralized connection admission control on Earth and an intelligent scheduling of the resource requests on board the satellite.  相似文献   
9.
Diabetes mellitus is a group of heterogeneous metabolic disorders characterized by chronic hyperglycaemia mainly due to pancreatic β cell death and/or dysfunction, caused by several types of stress such as glucotoxicity, lipotoxicity and inflammation. Different patho-physiological mechanisms driving β cell response to these stresses are tightly regulated by microRNAs (miRNAs), a class of negative regulators of gene expression, involved in pathogenic mechanisms occurring in diabetes and in its complications. In this review, we aim to shed light on the most important miRNAs regulating the maintenance and the robustness of β cell identity, as well as on those miRNAs involved in the pathogenesis of the two main forms of diabetes mellitus, i.e., type 1 and type 2 diabetes. Additionally, we acknowledge that the understanding of miRNAs-regulated molecular mechanisms is fundamental in order to develop specific and effective strategies based on miRNAs as therapeutic targets, employing innovative molecules.  相似文献   
10.
Multiple sclerosis is characterized by inflammatory demyelination and axonal loss as pathophysiological correlates of relapsing activity and progressive development of clinical disability. The molecular processes involved in this pathogenesis are still unclear as they are quite complex and heterogeneous. In this article we present protein expression analysis of brain and spinal cord tissues from different models of murine experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model for multiple sclerosis. We observed a number of EAE-specific protein expression and PTM differences. Proteome analysis was extended to multiple sclerosis specimens in order to validate the EAE findings. Our findings suggest the regulation of a number of proteins that shed light on the molecular mechanisms of the disease processes taking place in EAE and multiple sclerosis. We found consistent modulation of proteins including serum amyloid P component, sirtuin 2, dihydropyrimidinase-related protein family proteins, stathmin 1, creatine kinase B and chloride intracellular channel protein 1. Functional classification of the proteins by database and the literature mining reveals their association with neuronal development and myelinogenesis, suggesting possible disease processes that mediate neurodegeneration.  相似文献   
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