Road Infrastructure Safety Management. Proactive Safety Tools to Evaluate Potential Conditions of Risk

The identification of highly critical sections in a road network is possible by examining the network operation, with the goal of determining the risk factors and observe the critical issues, in order to better plan possible improvements. Therefore, this study proposes a method to evaluate the coherence of existing road layouts, through the analysis of the geometric characteristics, theoretical speeds and drivers operating speeds, under different environmental and flow conditions. The analysis focuses on the road network managed by ANAS SpA in the Veneto Region, for which the reconstruction of the road axes geometry, the curvature graph and the theoretical design speed profile have been obtained, according to the indications of the Italian Ministerial Decree 05/11/2001. The theoretical design speed profile has then been compared with the information relating to the road users' mobility, in terms of the 85th percentile speeds, obtained from the extraction and analysis of the Floating Car Data (FCD). The data were processed by reconstructing the continuous profile of operating speeds with a specific regression function known as "smoothing cubic spline". The comparison with the theoretical design speeds allows to observe whether the users assume a behavior close to or distant from what is expected, based on the technical and geometrical characteristics of the road layout. The proposed methodology can contribute to the implementation of a proactive road safety check, aimed at recognizing and assessing the potential risk conditions for road traffic, with particular attention to the point of view of the road user

Thymosin β4 and β10 in Sjögren's syndrome: Saliva proteomics and minor salivary glands expression

Background: In the present study, we investigated whether thymosin β (Tβ) in saliva and in minor salivary glands is differentially expressed in patients with primary Sjögren's syndrome (pSS) and patients with autoimmune diseases (systemic sclerosis [SSc], systemic lupus erythematosus [SLE], and rheumatoid arthritis [RA], with and without sicca syndrome [ss]). Methods: Saliva specimens of nine patients with pSS, seven with ss/SSc, seven with ss/SLE, seven with ss/RA, seven with SSc, seven with SLE, and seven with RA, as well as ten healthy subjects, were analyzed using a high-performance liquid chromatograph coupled with a mass spectrometer equipped with an electrospray ionization source to investigate the presence and levels of Tβ4, Tβ4 sulfoxide, and Tβ10. Immunostaining for Tβ4 and Tβ10 was performed on minor salivary glands of patients with pSS and ss. Results: Tβ4 levels were statistically higher in patients with pSS with respect to the other subgroups. Tβ10 was detectable in 66.7 % of patients with pSS and in 42.8 % of those with ss/SSc, while Tβ4 sulfoxide was detectable in 44.4 % of patients with pSS and in 42.9 % of those with ss/SSc. Tβ10 and Tβ4 sulfoxide were not detectable in patients without associated ss and in healthy control subjects. Regarding thymosin immunostaining, all patients had immunoreactivity for Tβ10, and a comparable distribution pattern in the four different subgroups of patients was observed. Tβ4 immunoreactivity was present in patients with ss/SSc and those with ss/SLE, while it was completely absent in patients with pSS and those with ss/RA. Conclusions: Our data show that higher salivary Tβ expression characterizes patients with pSS, while Tβ4 sulfoxide and Tβ10 salivary expression was selectively present in patients with sicca symptoms. Moreover, at the immunohistochemical level in patients with pSS, minor salivary glands showed a peculiar pattern characterized by immunostaining for Tβ10 in acinar cells in the absence of any reactivity for Tβ4. These findings, taken together, suggest a different role for Tβ4 and Tβ10 in patients with pSS who have ss and other autoimmune disease

Self-Assembly of Polyhedral Hybrid Colloidal Particles

We have developed a new method to produce hybrid particles with polyhedral shapes in very high yield (liter quantities at up to 70% purity) using a combination of emulsion polymerization and inorganic surface chemistry. The procedure has been generalized to create complex geometries, including hybrid line segments, triangles, tetrahedra, octahedra, and more. The optical properties of these particles are tailored for studying their dynamics and self-assembly. For example, we produce systems that consist of index-matched spheres allowing us to define the position of each elementary particle in three-dimensional space. We present some preliminary studies on the self-assembly of these complex shaped systems based on electron and optical microscopy.Engineering and Applied SciencesPhysic

LPS-induced IL-8 activation in human intestinal epithelial cells is accompanied by specific histone H3 acetylation and methylation changes

<p>Abstract</p> <p>Background</p> <p>The release of LPS by bacteria stimulates both immune and specific epithelial cell types to release inflammatory mediators. It is known that LPS induces the release of IL-8 by intestinal mucosal cells. Because it is now emerging that bacteria may induce alteration of epigenetic patterns in host cells, we have investigated whether LPS-induced IL-8 activation in human intestinal epithelial cells involves changes of histone modifications and/or DNA methylation at IL-8 gene regulatory region.</p> <p>Results</p> <p>RT-PCR analysis showed that IL-8 mRNA levels rapidly increase after exposure of HT-29 cells to LPS. DNA demethylating agents had no effects on IL-8 expression, suggesting that DNA methylation was not involved in IL-8 gene regulation. Consistently we found that 5 CpG sites located around IL-8 transcription start site (-83, -7, +73, +119, +191) were unmethylated on both lower and upper strand either in LPS treated or in untreated HT-29 cells, as well as in normal intestinal mucosa.</p> <p>Conversely, pretreatment of HT-29 cells with deacetylase inhibitors strengthened the LPS-mediated IL-8 activation. Inhibitors of histone deacetylases could induce IL-8 mRNA expression also in the absence of LPS, suggesting that chromatin modifications could be involved in IL-8 gene regulation. Chromatin immunoprecipitation analyses showed that, concurrently with IL-8 activation, transient specific changes in H3 acetylation and H3K4, H3K9 and H3K27 methylation occurred at IL-8 gene promoter during LPS stimulation. Changes of H3-acetyl, H3K4me2 and H3K9me2 levels occurred early, transiently and corresponded to transcriptional activity, while changes of H3K27me3 levels at IL-8 gene occurred later and were long lasting.</p> <p>Conclusion</p> <p>The results showed that specific chromatin modifications occurring at IL-8 gene, including histone H3 acetylation and methylation, mark LPS-mediated IL-8 activation in intestinal epithelial cells while it is unlikely that DNA methylation of IL-8 promoter is directly involved in IL-8 gene regulation in these cells.</p

Traversing the margins of corruption amidst informal economies in Amazonia

This article focuses on local idioms of extra-legal economic activity among indigenous Amazonians in eastern Peru, and its overall argument is that these idioms are part of a broader context in which indigenous people are compelled by a variety of factors to act in a seemingly corrupt manner. I further suggest that within such a context these idioms are not confined to the informal economy but are also used to refer to activities that fall within the formal economy, supporting Hart’s (2009) claim that the informal economy is a way of imagining the orthodox economy. I argue that corruption within Amazonian economies is commonly perceived by non-indigenous people as contrasting with the workings of the orthodox economy without proper consideration of the economic conditions and bureaucratic structures that give rise to it. Lastly, I argue that, here, corruption can contravene bureaucracy by restoring the humanity that Herzfeld (1993) claims bureaucracy rejects through its acts of indifference toward individuals

Proteomic and Biological Analysis of the Effects of Metformin Senomorphics on the Mesenchymal Stromal Cells

Senotherapeutics are new drugs that can modulate senescence phenomena within tissues and reduce the onset of age-related pathologies. Senotherapeutics are divided into senolytics and senomorphics. The senolytics selectively kill senescent cells, while the senomorphics delay or block the onset of senescence. Metformin has been used to treat diabetes for several decades. Recently, it has been proposed that metformin may have anti-aging properties as it prevents DNA damage and inflammation. We evaluated the senomorphic effect of 6&nbsp;weeks of therapeutic metformin treatment on the biology of human adipose mesenchymal stromal cells (MSCs). The study was combined with a proteome analysis of changes occurring in MSCs’ intracellular and secretome protein composition in order to identify molecular pathways associated with the observed biological phenomena. The metformin reduced the replicative senescence and cell death phenomena associated with prolonged in vitro cultivation. The continuous metformin supplementation delayed and/or reduced the impairment of MSC functions as evidenced by the presence of three specific pathways in metformin-treated samples: 1) the alpha-adrenergic signaling, which contributes to regulation of MSCs physiological secretory activity, 2) the signaling pathway associated with MSCs detoxification activity, and 3) the aspartate degradation pathway for optimal energy production. The senomorphic function of metformin seemed related to its reactive oxygen species (ROS) scavenging activity. In metformin-treated samples, the CEBPA, TP53 and USF1 transcription factors appeared to be involved in the regulation of several factors (SOD1, SOD2, CAT, GLRX, GSTP1) blocking ROS

8-Oxo-7,8-dihydro-2&apos;-deoxyguanosine and other lesions along the coding strand of the exon 5 of the tumour suppressor gene P53 in a breast cancer case-control study.

The next-generation sequencing studies of breast cancer have reported that the tumour suppressor P53 (TP53) gene is mutated in more than 40% of the tumours. We studied the levels of oxidative lesions, including 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG), along the coding strand of the exon 5 in breast cancer patients as well as in a reactive oxygen species (ROS)-attacked breast cancer cell line using the ligation-mediated polymerase chain reaction technique. We detected a significant ‘in vitro’ generation of 8-oxodG between the codons 163 and 175, corresponding to a TP53 region with high mutation prevalence, after treatment with xanthine plus xanthine oxidase, a ROS-generating system. Then, we evaluated the occurrence of oxidative lesions in the DNA-binding domain of the TP53 in the core needle biopsies of 113 of women undergoing breast investigation for diagnostic purpose. An increment of oxidative damage at the −G− residues into the codons 163 and 175 was found in the cancer cases as compared to the controls. We found significant associations with the pathological stage and the histological grade of tumours. As the major news of this study, this largest analysis of genomic footprinting of oxidative lesions at the TP53 sequence level to date provided a first roadmap describing the signatures of oxidative lesions in human breast cancer. Our results provide evidence that the generation of oxidative lesions at single nucleotide resolution is not an event highly stochastic, but causes a characteristic pattern of DNA lesions at the site of mutations in the TP53, suggesting causal relationship between oxidative DNA adducts and breast cancer

Ethical and practical considerations for mitigating risks to sexual partners during analytical treatment interruptions in HIV cure-related research

Background: Background: Analytical treatment interruptions (ATIs) in HIV cure-related research can result in trial participants becoming viremic with HIV, placing HIV-negative sexual partners at elevated risk of acquiring HIV. Objective: Objective:Our study aimed to generate ethical and practical considerations for designing and implementing appropriate risk mitigation strategies to reduce unintended HIV transmission events during ATIs. Methods: Methods: We conducted 21 in-depth interviews with five types of informants: bioethicists, community members, biomedical HIV cure researchers, socio-behavioral scientists/epidemiologists, and HIV care providers. We used conventional content analysis to analyze the data and generate considerations. Results: Results: Key findings include: 1) Ethical permissibility of ATI trials depends on due diligence and informed consent to mitigate risks to participants and their sexual partners; 2) Participants should receive adequate support and/or counseling if they choose to disclose ATI participation to their partners; 3) Measures to protect sexual partners of trial participants from HIV transmission during ATIs should include referral to and/or provision of pre-exposure prophylaxis, as well as other available means of preventing HIV transmission; 4) There is uncertainty regarding the appropriate management of emerging sexually transmitted infections during ATI trials and possible protection measures for multiple and/or anonymous partners of ATI trial participants. Conclusion: Conclusion: While there is no way to completely eliminate the risk of HIV transmission to sexual partners during ATIs, HIV cure trialists and sponsors should consider the ethical concerns related to the sexual partners of ATI participants. Doing so is essential to ensuring the welfare of participants, their partners and the trustworthiness of research