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Italy introduced the extensive use of speed bumps only in 1990, in an attempt to limit the high number of fatalities involving pedestrians in urban streets caused by the high speed of vehicles. In many countries, such devices have been the subject of careful investigations (in order to assess their effectiveness and disadvantages for the traffic circulation) and this has resulted in a number of modifications in the design to improve their performance. On the contrary, no systematic and scientific studies have been carried out on Italian installations: moreover, the type of undulation adopted is known to produce a series of problems for some categories of users and is not so effective in reducing speed as larger devices such as 'speed humps' or 'speed cushions'. This paper proposes a study of the effectiveness of 23 speed bumps installed in the city of Cagliari; to this aim, a speed analysis was performed at speed bump locations, at the crosswalks protected by the devices and at sections of the streets where bumps are installed but far from them. The results show that in one third of the cases the 85th percentile of speed measured at the speed bumps is higher than the posted speed limit (50 km/h) and an equal percentage of vehicles travel at a speed in the range of 45-50 km/h. No statistically significant differences were found from the comparison of speed values observed in free, bump or crosswalk sections of the same streets, while speed profiles calculated at four sites, where a high percentage of braking vehicles was observed, showed a common trend from which it clearly emerges that the effect of the device on driver's behaviour is restricted to a short spatial range (about 20-30 m before and after the bump). The current situation thus suggests the use of more effective devices such as humps or cushions, or the integration of speed bumps with other traffic calming techniques.  相似文献   
2.
Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and about 20% is metastatic at diagnosis and untreatable. Increasing evidence suggests that the heterogeneous nature of CRC is related to colorectal cancer stem cells (CCSCs), a small cells population with stemness behaviors and responsible for tumor progression, recurrence, and therapy resistance. Growing knowledge of stem cells (SCs) biology has rapidly improved uncovering the molecular mechanisms and possible crosstalk/feedback loops between signaling pathways that directly influence intestinal homeostasis and tumorigenesis. The generation of CCSCs is probably connected to genetic changes in members of signaling pathways, which control self-renewal and pluripotency in SCs and then establish function and phenotype of CCSCs. Particularly, various deregulated CCSC-related miRNAs have been reported to modulate stemness features, controlling CCSCs functions such as regulation of cell cycle genes expression, epithelial-mesenchymal transition, metastasization, and drug-resistance mechanisms. Primarily, CCSC-related miRNAs work by regulating mainly signal pathways known to be involved in CCSCs biology. This review intends to summarize the epigenetic findings linked to miRNAome in the maintenance and regulation of CCSCs, including their relationships with different signaling pathways, which should help to identify specific diagnostic, prognostic, and predictive biomarkers for CRC, but also develop innovative CCSCs-targeted therapies.  相似文献   
3.
Glaucoma is a group of ocular diseases characterized by an optic neuropathy in which degeneration of retinal ganglion cells leads to a characteristic excavation of the optic nerve head. Primary open-angle glaucoma (POAG) can be subdivided into two groups according to age of onset:- 1. the more common middle- to late-age onset, chronic open-angle glaucoma (COAG) diagnosed after the age of 40 years; 2. the rarer juvenile open-angle glaucoma (JOAG), which is diagnosed between the age of 3 years and early adulthood. Recently, the gene coding for the trabecular meshwork-induced glucocorticoid response protein (TIGR), located in chromosome 1 (1q23-25), was found mutated in patients affected by POAG. In this work we describe the clinical and molecular genetic features of several Italian families affected by autosomal dominant POAG, collected in various regions of Italy.  相似文献   
4.
Model checking, a prominent formal method used to predict and explain the behaviour of software and hardware systems, is examined on the basis of reflective work in the philosophy of science concerning the ontology of scientific theories and model-based reasoning. The empirical theories of computational systems that model checking techniques enable one to build are identified, in the light of the semantic conception of scientific theories, with families of models that are interconnected by simulation relations. And the mappings between these scientific theories and computational systems in their scope are analyzed in terms of suitable specializations of the notions of model of experiment and model of data. Furthermore, the extensively mechanized character of model-based reasoning in model checking is highlighted by a comparison with proof procedures adopted by other formal methods in computer science. Finally, potential epistemic benefits flowing from the application of model checking in other areas of scientific inquiry are emphasized in the context of computer simulation studies of biological information processing.  相似文献   
5.
Angius  Nicola 《Minds and Machines》2019,29(3):397-416

The Epistemology Of Computer Simulation (EOCS) has developed as an epistemological and methodological analysis of simulative sciences using quantitative computational models to represent and predict empirical phenomena of interest. In this paper, Executable Cell Biology (ECB) and Agent-Based Modelling (ABM) are examined to show how one may take advantage of qualitative computational models to evaluate reachability properties of reactive systems. In contrast to the thesis, advanced by EOCS, that computational models are not adequate representations of the simulated empirical systems, it is shown how the representational adequacy of qualitative models is essential to evaluate reachability properties. Justification theory, if not playing an essential role in EOCS, is exhibited to be involved in the process of advancing and corroborating model-based hypotheses about empirical systems in ECB and ABM. Finally, the practice of evaluating model-based hypothesis by testing the simulated systems is shown to constitute an argument in favour of the thesis that computer simulations in ECB and ABM can be put on a par with scientific experiments.

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6.
EGFR is overexpressed in the majority of clear cell renal cell carcinomas (CCRCCs). Although EGFR deregulation was found to be of great significance in CCRCC biology, the EGFR overexpression is not associated with EGFR-targeted therapy responsiveness. Moreover, the prognostic role of EGFR expression remains controversial. In the present study, we evaluated the role played by EGFR overexpression in CCRCC and its prognostic significance associated with different immunohistochemical localization patterns. In our study, the Total Score (TS) related to membranous-cytoplasmic EGFR expression showed a significant correlation with grade, pathologic stage (pT), and Stage, Size, Grade, and Necrosis (SSIGN) score, and a negative correlation with nuclear EGFR expression. No significant correlations were shown between nuclear EGFR and clinic-pathological features. Additionally, a correlation between SGLT1 expression levels and pT was described. Multivariate analysis identifies pT and SSIGN score as independent prognostic factors for CCRCC. A significantly increased survival rate was found in the case of positive expression of nuclear EGFR and SGLT1. Based on our findings, SGLT1 and nuclear EGFR overexpression defines a subgroup of CCRCC patients with good prognosis. Membranous-cytoplasmic EGFR expression was shown to be a poor prognostic factor and could define a CCRCC subgroup with poor prognosis that should be responsive to anti-EGFR therapies.  相似文献   
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Questions concerning the epistemological status of computer science are, in this paper, answered from the point of view of the formal verification framework. State space reduction techniques adopted to simplify computational models in model checking are analysed in terms of Aristotelian abstractions and Galilean idealizations characterizing the inquiry of empirical systems. Methodological considerations drawn here are employed to argue in favour of the scientific understanding of computer science as a discipline. Specifically, reduced models gained by Data Abstraction are acknowledged as Aristotelian abstractions that include only data which are sufficient to examine the interested executions. The present study highlights how the need to maximize incompatible properties is at the basis of both Abstraction Refinement, the process of generating a cascade of computational models to achieve a balance between simplicity and informativeness, and the Multiple Model Idealization approach in biology. Finally, fairness constraints, imposed to computational models to allow fair behaviours only, are defined as ceteris paribus conditions under which temporal formulas, formalizing software requirements, acquire the status of law-like statements about the software systems executions.  相似文献   
9.
S. Ippagunta  Z. Angius  M. Sanda  K. M. Barnes 《Lipids》2013,48(11):1145-1155
Conjugated linoleic acid (CLA) has been shown to cause a reduction in obesity in several species. CLA-induced body fat loss is enhanced when mice are fed coconut oil (CO) and involves increased lipolysis. The objective of this paper was to determine if the CLA-induced lipolysis in mice fed with different oil sources was time-dependent. Mice were fed 7 % soybean oil (SO) or CO diets for 6 week and then supplemented with 0 or 0.5 % CLA for 3, 7, 10 or 14 days. Body fat and ex-vivo lipolysis was determined. Body fat was reduced by CO on day 7 (P < 0.01) and in both CO and SO-fed mice (P < 0.05) in response to CLA on d14. Lipolysis was increased by CLA in CO-fed mice (P < 0.01) but not in SO-fed mice on day 7 and 10, but on day 14 CLA increased lipolysis in both CO- and SO-fed mice (P < 0.001). Expression and activation level of proteins involved in lipolysis and lipogenesis was determined by western blotting and real-time PCR, respectively. No significant differences were detected in protein expression. CO-fed mice had greater fatty acid synthase and stearyl CoA desaturase 1 mRNA expression and less acetyl CoA carboxylase mRNA expression (P < 0.01). Sterol regulatory binding protein 1c was decreased by CLA in CO-fed mice and increased in SO-fed mice (P < 0.05). Malic enzyme expression was increased by CLA (P < 0.001) and CO (P < 0.01). Therefore, CLA-induced lipolysis occurs more rapidly in CO vs SO-fed mice and lipogenesis is decreased in CO-fed mice with CLA supplementation.  相似文献   
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