Microrna isoforms contribution to melanoma pathogenesis

Cutaneous melanoma (CM) is the most lethal tumor among skin cancers, and its incidence is constantly increasing. A deeper understanding of the molecular processes guiding melanoma pathogenesis could improve diagnosis, treatment and prognosis. MicroRNAs play a key role in melanoma biology. Recently, next generation sequencing (NGS) experiments, designed to assess small‐RNA expression, revealed the existence of microRNA variants with different length and sequence. These microRNA isoforms are known as isomiRs and provide an additional layer to the complex non‐coding RNA world. Here, we collected data from NGS experiments to provide a comprehensive characterization of miRNA and isomiR dysregulation in benign nevi (BN) and early-stage melanomas. We observed that melanoma and BN express different and specific isomiRs and have a different isomiR abundance distribution. Moreover, isomiRs from the same microRNA can have opposite expression trends between groups. Using The Cancer Genome Atlas (TCGA) dataset of skin cancers, we analyzed isomiR expression in primary melanoma and melanoma metastasis and tested their association with NF1, BRAF and NRAS mutations. IsomiRs differentially expressed were identified and catalogued with reference to the canonical form. The reported non‐random dysregulation of specific isomiRs contributes to the understanding of the complex melanoma pathogenesis and serves as the basis for further functional studies

Response to Kestens et al. Comments on Melis et al. The effects of the Urban Built Environment on Mental Health: A Cohort Study in a Large Northern Italian City. Int J Environ Res Public Health 2015, 12, 14898-14915

The commentary from Kestens et al. [1] raises interesting issues about measuring contextual exposures and encourages new studies to incorporate them in their design: as a group of researchers, we strongly support their view and think that those useful reflections should be used as guidelines for future research.[...

Efficiency, products and mechanisms of ethyl acetate oxidative degradation in air non-thermal plasma

Ethyl acetate (EA) is a popular solvent and diluent in many products and one of the most ubiquitous organic pollutants of indoor air. Although EA's ascertained toxicity is classified as low, exposure to its vapors at concentrations 400 ppm causes serious problems in humans. EA is thus a frequent target in testing novel technologies for air purification. We report here an investigation of EA oxidative degradation in air at room temperature and atmospheric pressure induced by corona discharges. Three corona regimes, dc-, dc+ and pulsed +, were tested in the same reactor under various experimental conditions with regard to EA initial concentration (C 0) and the presence of humidity in the system. The EA degradation process was monitored by gas chromatography (GC)-flame ionization detection, GC-mass spectrometry and Fourier transform infrared spectroscopy analysis of the treated gas. These analyses yielded the concentration of residual EA (C) and those of its major products of oxidation (CO2, CO) and revealed a few organic reaction intermediates formed along the oxidation chain. The process energy efficiency was determined as energy constant, k E (kJ-1 l) and as energy yield, EY (g kW-1 h-1). The efficiency depends on the type of corona (pulsed + >dc- >dc+), on the presence of humidity in the air (improvement in the case of dc-, little or no effect for dc+) and on C 0 (k E increases linearly with 1/C 0). CO2 and CO were the major carbon containing products, confirming the strong oxidizing power of air non-thermal plasma. Acetic acid and acetaldehyde were detected in very small amounts as reaction intermediates. The experimental results obtained in this work support the conclusion that different reactive species are involved in the initial step of EA oxidation in the case of dc- and dc+ corona air non-thermal plasma

Social inequalities in heat-attributable mortality in the city of Turin, northwest of Italy: a time series analysis from 1982 to 2018

Background: Understanding context specific heat-health risks in urban areas is important, especially given anticipated severe increases in summer temperatures due to climate change effects. We investigate social inequalities in the association between daily temperatures and mortality in summer in the city of Turin for the period 1982–2018 among different social and demographic groups such as sex, age, educational level, marital status and household occupants. Methods: Mortality data are represented by individual all-cause mortality counts for the summer months between 1982 and 2018. Socioeconomic level and daily mean temperature were assigned to each deceased. A time series Poisson regression with distributed lag non-linear models was fitted to capture the complex nonlinear dependency between daily mortality and temperature in summer. The mortality risk due to heat is represented by the Relative Risk (RR) at the 99th percentile of daily summer temperatures for each population subgroup. Results: All-cause mortality risk is higher among women (1.88; 95% CI = 1.77, 2.00) and the elderly (2.13; 95% CI = 1.94, 2.33). With regard to education, the highest significant effects for men is observed among higher education levels (1.66; 95% CI = 1.38, 1.99), while risks for women is higher for the lower educational level (1.93; 95% CI = 1.79, 2.08). Results on marital status highlighted a stronger association for widower in men (1.66; 95% CI = 1.38, 2.00) and for separated and divorced in women (2.11; 95% CI = 1.51, 2.94). The risk ratio of household occupants reveals a stronger association for men who lived alone (1.61; 95% CI = 1.39, 1.86), while for women results are almost equivalent between alone and not alone groups. Conclusions: The associations between heat and mortality is unequal across different aspects of social vulnerability, and, inter alia, factors influencing the population vulnerability to temperatures can be related to demographic, social, and economic aspects. A number of issues are identified and recommendations for the prioritisation of further research are provided. A better knowledge of these effect modifiers is needed to identify the axes of social inequality across the most vulnerable population sub-groups

Basal cell carcinoma: A comprehensive review

Basal cell carcinoma (BCC) is the most common type of carcinoma worldwide. BCC development is the result of a complex interaction between environmental, phenotypic and genetic factors. However, despite the progress in the field, BCC biology and mechanisms of resistance against systemic treatments have been poorly investigated. The aim of the present review is to provide a revision of BCC histological and molecular features, including microRNA (miRNA) dysregulation, with a specific focus on the molecular basis of BCC systemic therapies. Papers from the last ten years regarding BCC genetic and phenotypic alterations, as well as the mechanism of resistance against hedgehog pathway inhibitors vismodegib and sonidegib were included. The involvement of miRNAs in BCC resistance to systemic therapies is emerging as a new field of knowledge

Design of Nb3Sn Coils for LARP Long Magnets

The LHC Accelerator Research Program (LARP) has a primary goal to develop, assemble, and test full size Nb{sub 3}Sn quadrupole magnet models for a luminosity upgrade of the Large Hadron Collider (LHC). A major milestone in this development is to assemble and test, by the end of 2009, two 4 m-long quadrupole cold masses, which will be the first Nb{sub 3}Sn accelerator magnet models approaching the length of real accelerator magnets. The design is based on the LARP Technological Quadrupoles (TQ), under development at FNAL and LBNL, with gradient higher than 200 T/m and aperture of 90 mm. The mechanical design will be chosen between two designs presently explored for the TQs: traditional collars and Al-shell based design (preloaded by bladders and keys). The fabrication of the first long quadrupole model is expected to start in the last quarter of 2007. Meanwhile the fabrication of 4 m-long racetrack coils started this year at BNL. These coils will be tested in an Al-shell based supporting structure developed at LBNL. Several challenges have to be addressed for the successful fabrication of long Nb{sub 3}Sn coils. This paper presents these challenges with comments and solutions adopted or under study for these magnets. The coil design of these magnets, including conductor and insulation features, and quench protection studies are also presented

Second-Generation Coil Design of the Nb3Sn low-β Quadrupole for the High Luminosity LHC

As part of the Large Hadron Collider (LHC) Luminosity upgrade program, the U.S.-LHC Accelerator Research Program collaboration and CERN are working together to design and build a 150-mm aperture Nb3Sn quadrupole for the LHC interaction regions. A first series of 1.5-m-long coils was fabricated and assembled in a first short model. A detailed visual inspection of the coils was carried out to investigate cable dimensional changes during heat treatment and the position of the windings in the coil straight section and in the end region. The analyses allow identifying a set of design changes which, combined with a fine tune of the cable geometry and a field quality optimization, were implemented in a new second-generation coil design. In this paper, we review the main characteristics of the first generation coils, describe the modification in coil layout and discuss their impact on parts design and magnet analysis

Overview of the Quench Heater Performance for MQXF, the Nb3Sn Low-β Quadrupole for the High Luminosity LHC

In the framework of the high-luminosity upgrade of the Large Hadron Collider, the U.S. LARP collaboration and CERN are jointly developing a 150 mm aperture Nb Sn quadrupole for the LHC interaction regions. Due to the large stored energy density and the low copper stabilizer section, the quench protection of these magnets is particularly challenging, relying on a combination of quench heaters attached to the coil surface and coupling loss induced quench (CLIQ) units electrically connected to the coils. This paper summarizes the performance of the quench heater strips in different configurations relevant to machine operation. The analysis is focused on the inner layer quench heaters, where several heater strips failed during powering tests. Failure modes are discussed in order to address the technology issues and provide guidance for future tests.

Mechanical Design Analysis of MQXFB, the 7.2-m-Long Low-β Quadrupole for the High-Luminosity LHC Upgrade

As part of the High-Luminosity Large Hadron Collider (LHC) Project, a set of Nb Snquadrupoles are being developed, aiming to enhance the performance of the inner triplets. The new magnets, identified as MQXFA and MQXFB, will share the same cross section with two different lengths, 4.2 and 7.2 m, respectively. During the magnet development, three short models were tested, along with a number of mechanical models, demonstrating the capability of the magnet cross section to achieve the specified performances. The same performances are now required for the full-length magnets. To ensure this, the authors studied the impact of the magnet length on the capability of the structure to provide an adequate support to the coils. Finite element and simplified analytical models were used to evaluate the impact of the magnet length on the stresses in the magnet ends and coil elongation during powering. The models were calibrated using the results from the short model tests, and used to provide an indication on the required prestress and its foreseen impact on the magnet performance.