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After the European Environmental Noise Directive prescribed noise maps and action plans, wide scientific literature and a consistent number of mitigation strategies emerged for road, railway, airport, and industrial noise. Unfortunately, very little attention has been paid to the noise produced by ports in their surroundings, even though there could be many areas affected by it. At present, more attention seems to be paid to noise produced underwater, mostly for military and security reasons and for its interference with wildlife, rather than airborne noise and its influence on human health. In the framework of a project aiming to shed more light on a topic so far under-investigated, this paper presents an acoustical characterization of different small vessels at various speeds that move around on a daily basis in every type of port, produced by means of short- and long-term measurements. The new information acquired was used to produce a map of noise generated by vessels moving in Livorno’s canals, which branch off in a densely inhabited area. The simulations were validated using long-term measurement. The number of citizens exposed was also estimated and used to calculate the number of highly annoyed people according to the recent curve for road traffic noise proposed by Guski et al. In order to prevent citizen exposure to noise and possible complaints about small boats, different scenarios and possible future situations such as various vessel speeds, limited flow, restricted areas for some categories, or new residential areas were studied.

In the light of sustainability, satisfactory living conditions is an important factor for people’s positive feedback in their own living environment. Acoustic comfort and noise exposure should then be carefully monitored in all human settlements. Furthermore, it is already well-known that high or prolonged noise levels may lead to unwanted health effects. Unfortunately, while in the last decades scientists and public authorities have investigated the noise produced by roads, trains, and airports, not enough efforts have been spent in studying what happens around the coastal and port areas. Following the attention brought to the subject by recent European projects on noise in port areas, the present paper characterizes the sound power level and 1/3 octave band sound power spectrum of seagoing ships while moving at low speeds. Five different categories have been distinguished: Roll-on/roll-off (RORO), container ship, oil tanker, chemical tanker, and ferry. The analysis is based on a continuous noise measurement lasting more than three months, performed in the industrial canal of the port of Livorno (Italy). The resulting noise emissions are new and useful data that could be inserted in acoustic propagation models to properly assess the noise in the areas affected by port activities. Thus, the present work can act as a supporting tool in planning ship traffic in ports towards better sustainability.

Only recently has noise been considered in the assessment of the sustainability of port infrastructures, after decades of unawareness. INTERREG Maritime projects unveiled problems that have been neglected so far, such as the lack of proper regulation and noise exposure assessments for citizens. While it is true that a port area includes a huge variety of possible noise sources, very few of them have been characterized from an acoustical point of view. INTERREG projects have boosted research in the field, and previous studies have dealt with noise produced by moving ships in ports. The present work starts from a previous measurement campaign used to obtain broadband and 1/3-octave-band noise emissions of moving ships, and it aims to explain their uncertainties. More than a month’s worth of continuous acoustic measurements and video recordings were deeply analyzed in order to obtain an input database that is as precise as possible. A multiple regression analysis was performed in order to understand the influence that parameters such as minimum distance, speed, and draught have on ships’ noise emissions, which were calculated using pass-by measurements, with a special focus on ferries. The minimum distance of each ship’s passage from the microphone was measured using a video recording with an innovative methodology, providing results with 3 m of uncertainty. Knowing which parameter is more influential would help in planning proper measurements for monitoring or for drafting correct guidelines. Draught was determined to be uninfluential in ferries’ noise emissions, while the minimum distance and speed relations were estimated and accounted for in the calculation of a refined sound power level. From a spectrum point of view, the frequencies from 500 Hz to 2.5 kHz were determined to be those that contributed the most to the noise produced by the transit of a ship, and they vary with speed. With the studied corrections, different ferry models resulted in similar noise emissions. The standard deviation of noise emitted was reduced by 0.5 dB (A), and the average was also improved by positioning the ships’ flow at the correct average minimum distance. Furthermore, the right placement of a source is also important in the acoustic mapping phase for a correct evaluation of the propagation of noise at a distance. The use of more precise input data is important for improving the output of acoustic propagation models during the assessment of port noise in the surrounding areas.

The gut microbiota is essential for human health and plays an important role in the pathogenesis of several diseases. Short-chain fatty acids (SCFA), such as acetate, butyrate and propionate, are end-products of microbial fermentation of macronutrients that distribute systemically via the blood. The aim of this study was to investigate the transcriptional response of immature and LPS-matured human monocyte-derived DC to SCFA. Our data revealed distinct effects exerted by each individual SCFA on gene expression in human monocyte-derived DC, especially in the mature ones. Acetate only exerted negligible effects, while both butyrate and propionate strongly modulated gene expression in both immature and mature human monocyte-derived DC. An Ingenuity pathway analysis based on the differentially expressed genes suggested that propionate and butyrate modulate leukocyte trafficking, as SCFA strongly reduced the release of several pro-inflammatory chemokines including CCL3, CCL4, CCL5, CXCL9, CXCL10 and CXCL11. Additionally, butyrate and propionate inhibited the expression of lipopolysaccharide (LPS)-induced cytokines such as IL-6 and IL-12p40 showing a strong anti-inflammatory effect. This work illustrates that bacterial metabolites far from the site of their production can differentially modulate the inflammatory response and generally provides new insights into host-microbiome interactions.

Purpose The purpose of this paper is to simulate charge transport in monolayer graphene on a substrate made of hexagonal boron nitride (h-BN). This choice is motivated by the fact that h-BN is one of the most promising substrates on account of the reduced degradation of the velocity due to the remote impurities. Design/methodology/approach The semiclassical Boltzmann equations for electrons in the monolayer graphene are numerically solved by an approach based on a discontinuous Galerkin (DG) method. Both the conduction and valence bands are included, and the inter-band scatterings are taken into account as well. Findings The importance of the inter-band scatterings is accurately evaluated for several values of the Fermi energy, addressing the issue related to the validity of neglecting the generation-recombination terms. It is found out that the inclusion of the inter-band scatterings produces sizable variations in the average values, like the current density, at zero Fermi energy, whereas, as expected, the effect of the inter-band scattering becomes negligible by increasing the absolute value of the Fermi energy. Research limitations/implications The correct evaluation of the influence of the inter-band scatterings on the electronic performances is deeply important not only from a theoretical point of view but also for the applications. In particular, it will be shown that the time necessary to reach the steady state is greatly affected by the inter-band scatterings, with not negligible consequences on the switching on/off processes of realistic devices. As a limitation of the present work, the proposed approach refers to the spatially homogeneous case. For the simulation of electron devices, non-homogenous numerical solutions are required. This last case will be tackled in a forthcoming paper. Originality/value As observed in Majorana et al. (2019), the use of a Direct Simulation Monte Carlo (DSMC) approach, which properly describes the inter-band scatterings, is computationally very expensive because the valence band is highly populated and a huge number of particles is needed. Even by simulating holes instead of electrons does not overcome the problem because there is a certain degree of ambiguity in the generation and recombination terms of electron-hole pairs. The DG approach, used in this paper, does not suffer from the previous drawbacks and requires a reasonable computing effort.

Bacterial genotoxins, produced by several Gram-negative bacteria, induce DNA damage in the target cells. While the responses induced in the host cells have been extensively studied in vitro, the role of these effectors during the course of infection remains poorly characterized. To address this issue, we assessed the effects of the Salmonella enterica genotoxin, known as typhoid toxin, in in vivo models of murine infection. Immunocompetent mice were infected with isogenic S. enterica, serovar Typhimurium (S. Typhimurium) strains, encoding either a functional or an inactive typhoid toxin. The presence of the genotoxic subunit was detected 10 days post-infection in the liver of infected mice. Unexpectedly, its expression promoted the survival of the host, and was associated with a significant reduction of severe enteritis in the early phases of infection. Immunohistochemical and transcriptomic analysis confirmed the toxin-mediated suppression of the intestinal inflammatory response. The presence of a functional typhoid toxin further induced an increased frequency of asymptomatic carriers. Our data indicate that the typhoid toxin DNA damaging activity increases host survival and favours long-term colonization, highlighting a complex cross-talk between infection, DNA damage response and host immune response. These findings may contribute to understand why such effectors have been evolutionary conserved and horizontally transferred among Gram-negative bacteria.

Background Gastric-cancer is a heterogeneous type of neoplastic disease and it lacks appropriate therapeutic options. There is an urgent need for the development of innovative pharmacological strategies, particularly in consideration of the potential stratified/personalized treatment of this tumor. All-Trans Retinoic-acid (ATRA) is one of the active metabolites of vitamin-A. This natural compound is the first example of clinically approved cyto-differentiating agent, being used in the treatment of acute promyelocytic leukemia. ATRA may have significant therapeutic potential also in the context of solid tumors, including gastric-cancer. The present study provides pre-clinical evidence supporting the use of ATRA in the treatment of gastric-cancer using high-throughput approaches. Methods We evaluated the anti-proliferative action of ATRA in 27 gastric-cancer cell-lines and tissue-slice cultures from 13 gastric-cancer patients. We performed RNA-sequencing studies in 13 cell-lines exposed to ATRA. We used these and the gastric-cancer RNA-sequencing data of the TCGA / CCLE datasets to conduct multiple computational analyses. Results Profiling of our large panel of gastric-cancer cell-lines for their quantitative response to the anti-proliferative effects of ATRA indicate that approximately half of the cell-lines are characterized by sensitivity to the retinoid. The constitutive transcriptomic profiles of these cell-lines permitted the construction of a model consisting of 42 genes, whose expression correlates with ATRA -sensitivity.  The model predicts that 45% of the TCGA gastric-cancers are sensitive to ATRA. RNA-sequencing studies performed in retinoid-treated gastric-cancer cell-lines provide insights into the gene-networks underlying ATRA anti-tumor activity. In addition, our data demonstrate that ATRA exerts significant immune-modulatory effects, which seem to be largely controlled by IRF1 up-regulation. Finally, we provide evidence of a feed-back loop between IRF1 and DHRS3 , another gene which is up-regulated by ATRA. Conclusions ATRA is endowed with significant therapeutic potential in the stratified/personalized treatment gastric-cancer. Our data represent the fundaments for the design of clinical trials focusing on the use of ATRA in the personalized treatment of this heterogeneous tumor. Our gene-expression model will permit the development of a predictive tool for the selection of ATRA-sensitive gastric-cancer patients. The immune-regulatory responses activated by ATRA suggest that the retinoid and immune-checkpoint inhibitors constitute rational combinations for the management of gastric-cancer.

Neuroblastoma (NB) is a heterogeneous extracranial tumor occurring in childhood. A distinctive feature of NB tumors is their neuroendocrine ability to secrete catecholamines, which in turn, via β-adrenergic receptors ligation, may affect different signaling pathways in tumor microenvironment (TME). It was previously demonstrated that specific antagonism of β3-adrenergic receptor (β3-AR) on NB tumor cells affected tumor growth and progression. Here, in a murine syngeneic model of NB, we aimed to investigate whether the β3-AR modulation influenced the host immune system response against tumor. Results demonstrated that β3-AR antagonism lead to an immune response reactivation, partially dependent on the PD-1/PD-L1 signaling axis involvement. Indeed, β3-AR blockade on tumor-infiltrating lymphocytes (TILs) dampened their ability to secrete IFN-γ, which in turn reduced the PD-L1 expression, caused by TILs infiltration, on NB tumor cells. Further investigations, through a genomic analysis on NB patients, showed that high ADRB3 gene expression correlates with worse clinical outcome compared to the low expression group, and that ADRB3 gene expression affects different immune-related pathways. Overall, results indicate that β3-AR in NB TME is able to modulate the interaction between tumor and host immune system, and that its antagonism hits multiple pro-tumoral signaling pathways.

In this study, two boronic acid BODIPYs are obtained through a microwave-assisted Knoevenagel reaction. The aim is to use them for the first time as dyes in a photosensitized solar cell (DSSC) to mimic chlorophyll photosynthesis, harvesting solar light and converting it into electricity. The microwave-assisted Knoevenagel reaction is a straightforward approach to extending the molecular conjugation of the dye and is applied for the first time to synthesize BODIPY’s boronic acid derivatives. These derivatives have proved to be very useful for covalent deposition on titania. This work studies the photo-physical and electrochemical properties. Moreover, the photovoltaic performances of these two new dyes as sensitizers for DSSC are discussed. Experimental data show that both dyes exhibit photosensitizing activities in acetonitrile and water. In particular, in all the experiments, distyryl BODIPY was more efficient than styryl BODIPY. In this study, demonstrating the use of a natural component as a water-based electrolyte for boronic BODIPY sensitizers, we open new possibilities for the development of water-based solar cells.

Non-motor symptoms are gaining relevance in Parkinson’s disease (PD) management but little is known about their progression and contribution to deterioration of quality of life. We followed prospectively 707 PD patients (62 % males) for 2 years. We assessed non-motor symptoms referred to 12 different domains, each including 1–10 specific symptoms, as well as motor state (UPDRS), general cognition, and life quality. Hoehn & Yahr (H&Y) stage was used to categorize patient status (I–II mild; III moderate; IV–V severe). We found that individual non-motor symptoms had variable evolution over the 2-year follow-up with sleep, gastrointestinal, attention/memory and skin disturbances (hyperhidrosis and seborrhea) becoming more prevalent and psychiatric, cardiovascular, and respiratory disorders becoming less prevalent. Development of symptoms in the cardiovascular, apathy, urinary, psychiatric, and fatigue domains was associated with significant life-quality worsening ( p  < 0.0045, alpha with Bonferroni correction). During the observation period, 123 patients (17 %) worsened clinically while 584 were rated as stable. There was a fivefold greater increase in UPDRS motor score in worse compared with stable patients over 24 months ( p  < 0.0001 vs. baseline both in stable and worse group). The total number of reported non-motor symptoms increased over 24 months in patients with motor worsening compared to stable ones ( p  < 0.001). Thirty-nine patients died (3.4 % of patients evaluable at baseline) with mean age at death of 74 years. Deceased patients were older, had significantly higher H&Y stage and motor score, and reported a greater number of non-motor symptoms at baseline. In conclusion, overall non-motor symptom progression does not follow motor deterioration, is symptom-specific, and only development of specific domains negatively impacts quality of life. These results have consequences for drug studies targeting non-motor features.