Design of X-Concentric Braced Steel Frame Systems Using an Equivalent Stiffness in a Modal Elastic Analysis

In this work, a general method for the design of concentric braced steel frames (CBF) with active tension diagonal bracings, applicable to single- and multi-storey structures, is presented. The method is based on the use of an elastic modal analysis with a response spectrum, which is carried out using an appropriate modified elastic stiffness of diagonal bracings. The reliability of the proposed method is validated through the analysis of significant case studies, making a series of numerical comparisons carrying out time-history non-linear dynamic analysis

A STUDY OF THE MECHANICAL ENERGY DIFFERENCES BETWEEN TREADMILL AND OVERGROUND WALKING

The aim of this paper was to analyze the components of the mechanical energy of the body considering the differences between treadmill and overground walking. One subject was filmed while walking at 1.5 m/s on treadmill and overground. The results show that the patterns of the curves are very similar, but the change in the total energy, both in the upper as in the lower extremity were greater on overground (23.20J and 17.47J respectively for overground and treadmill and for the upper extremity 4.91J and 2.56J). The potential energy change of the trunk was also greater on overground (overground 45.97J; treadmill 24.88J). These findings, showing a lower measured mechanical cost on treadmill address the problem whether the treadmill can be used as a valid simulator for overground walking

Resource Control for Synchronous Cooperative Threads

We develop new methods to statically bound the resources needed for the execution of systems of concurrent, interactive threads. Our study is concerned with a \emph{synchronous} model of interaction based on cooperative threads whose execution proceeds in synchronous rounds called instants. Our contribution is a system of compositional static analyses to guarantee that each instant terminates and to bound the size of the values computed by the system as a function of the size of its parameters at the beginning of the instant. Our method generalises an approach designed for first-order functional languages that relies on a combination of standard termination techniques for term rewriting systems and an analysis of the size of the computed values based on the notion of quasi-interpretation. We show that these two methods can be combined to obtain an explicit polynomial bound on the resources needed for the execution of the system during an instant. As a second contribution, we introduce a virtual machine and a related bytecode thus producing a precise description of the resources needed for the execution of a system. In this context, we present a suitable control flow analysis that allows to formulte the static analyses for resource control at byte code level

Cost-benefit analysis of coastal flood defence measures in the North Adriatic Sea

The combined effect of global sea level rise and land subsidence phenomena poses a major threat to coastal settlements. Coastal flooding events are expected to grow in frequency and magnitude, increasing the potential economic losses and costs of adaptation. In Italy, a large share of the population and economic activities are located along the low-lying coastal plain of the North Adriatic coast, one of the most sensitive areas to relative sea level changes. Over the last half a century, this stretch of coast has experienced a significant rise in relative sea level, the main component of which was land subsidence; in the forthcoming decades, climate-induced sea level rise is expected to become the first driver of coastal inundation hazard. We propose an assessment of flood hazard and risk linked with extreme sea level scenarios, under both historical conditions and sea level rise projections in 2050 and 2100. We run a hydrodynamic inundation model on two pilot sites located along the North Adriatic coast of Emilia-Romagna: Rimini and Cesenatico. Here, we compare alternative extreme sea level scenarios accounting for the effect of planned and hypothetical seaside renovation projects against the historical baseline. We apply a flood damage model to estimate the potential economic damage linked to flood scenarios, and we calculate the change in expected annual damage according to changes in the relative sea level. Finally, damage reduction benefits are evaluated by means of cost-benefit analysis. Results suggest an overall profitability of the investigated projects over time, with increasing benefits due to increased probability of intense flooding in the near future

Eye-Light on Age-Related Macular Degeneration: Targeting Nrf2-Pathway as a Novel Therapeutic Strategy for Retinal Pigment Epithelium

open6noThis work was supported by the University of Pavia [to MA, grant number BSR1744747; 2017] and the Italian Ministry of University and Research [to MA, FFABR2017]. The University of Bologna is acknowledged by MR [Grants from RFO].Age-related macular degeneration (AMD) is a common disease with a multifactorial aetiology, still lacking effective and curative therapies. Among the early events triggering AMD is the deterioration of the retinal pigment epithelium (RPE), whose fundamental functions assure good health of the retina. RPE is physiologically exposed to high levels of oxidative stress during its lifespan; thus, the integrity and well-functioning of its antioxidant systems are crucial to maintain RPE homeostasis. Among these defensive systems, the Nrf2-pathway plays a primary role. Literature evidence suggests that, in aged and especially in AMD RPE, there is an imbalance between the increased pro-oxidant stress, and the impaired endogenous detoxifying systems, finally reverberating on RPE functions and survival. In this in vitro study on wild type (WT) and Nrf2-silenced (siNrf2) ARPE-19 cells exposed to various AMD-related noxae (H2O2, 4-HNE, MG132 + Bafilomycin), we show that the Nrf2-pathway activation is a physiological protective stress response, leading downstream to an up-regulation of the Nrf2-targets HO1 and p62, and that a Nrf2 impairment predisposes the cells to a higher vulnerability to stress. In search of new pharmacologically active compounds potentially useful for AMD, four nature-inspired hybrids (NIH) were individually characterized as Nrf2 activators, and their pharmacological activity was investigated in ARPE-19 cells. The Nrf2 activator dimethyl-fumarate (DMF; 10 μM) was used as a positive control. Three out of the four tested NIH (5 μM) display both direct and indirect antioxidant properties, in addition to cytoprotective effects in ARPE-19 cells under pro-oxidant stimuli. The observed pro-survival effects require the presence of Nrf2, with the exception of the lead compound NIH1, able to exert a still significant, albeit lower, protection even in siNrf2 cells, supporting the concept of the existence of both Nrf2-dependent and independent pathways mediating pro-survival effects. In conclusion, by using some pharmacological tools as well as a reference compound, we dissected the role of the Nrf2-pathway in ARPE-19 stress response, suggesting that the Nrf2 induction represents an efficient defensive strategy to prevent the stress-induced damage.openCatanzaro M.; Lanni C.; Basagni F.; Rosini M.; Govoni S.; Amadio M.Catanzaro M.; Lanni C.; Basagni F.; Rosini M.; Govoni S.; Amadio M

Batalin-Vilkovisky Integrals in Finite Dimensions

The Batalin-Vilkovisky method (BV) is the most powerful method to analyze functional integrals with (infinite-dimensional) gauge symmetries presently known. It has been invented to fix gauges associated with symmetries that do not close off-shell. Homological Perturbation Theory is introduced and used to develop the integration theory behind BV and to describe the BV quantization of a Lagrangian system with symmetries. Localization (illustrated in terms of Duistermaat-Heckman localization) as well as anomalous symmetries are discussed in the framework of BV.Comment: 35 page

CXCL5-mediated accumulation of mature neutrophils in lung cancer tissues impairs the differentiation program of anticancer CD8 T cells and limits the efficacy of checkpoint inhibitors

Lung tumor-infiltrating neutrophils are known to support growth and dissemination of cancer cells and to suppress T cell responses. However, the precise impact of tissue neutrophils on programming and differentiation of anticancer CD8 T cells in vivo remains poorly understood. Here, we identified cancer cell-autonomous secretion of CXCL5 as sufficient to drive infiltration of mature, protumorigenic neutrophils in a mouse model of non-small cell lung cancer (NSCLC). Consistently, CXCL5 transcripts correlate with neutrophil density and poor prognosis in a large human lung adenocarcinoma compendium. CXCL5 genetic deletion, unlike antibody-mediated depletion, completely and selectively prevented neutrophils accumulation in lung tissues. Depletion of tumor-infiltrating neutrophils promoted expansion of tumor-specific CD8 T cells, differentiation into effector cells and acquisition of cytolytic functions. Transfer of effector CD8 T cells into neutrophil-rich tumors, inhibited IFN-ϒ production, indicating active suppression of effector functions. Importantly, blocking neutrophils infiltration in the lung, overcame resistance to checkpoint blockade. Hence, this study demonstrates that neutrophils curb acquisition of cytolytic functions in lung tumor tissues and suggests targeting of CXCL5 as a strategy to restore anti-tumoral T cell functions

Anticancer activity of "Trigno M", extract of Prunus spinosa drupes, against in vitro 3D and in vivo colon cancer models

Abstract In 2018 there were over 1.8 million new cases worldwide of colorectal cancer and relapses after clinical treatments. Many studies ascribe the risk of the appearance of this cancer to the Western life style : a sedentary life, obesity, and low -fiber, high -fat diets can promote the onset of disease. Several studies have shown supplement phytochemicals to have an inhibiting effect on the growth of various cancers through the activation of apoptosis. Our goal was to prove the effectiveness of a natural compound in the combined therapy of colorectal cancer. Trigno M supplement was an optimal candidate as anticancer product for its high concentrations of phenolic acids, flavonoids and anthocyanins. Our work showed the antitumor activity of Trigno M, extract of Prunus spinosa drupes combined with the nutraceutical activator complex (NAC), in 2D, 3D and in vivo colorectal cancer models. The cellular model we used both in vitro and in vivo was the HCT116 cell line, particularly suitable for engraftment after inoculation in mice. Trigno M inhibited the growth and colony formation of HCT116 cells (35%) as compared to the chemotherapy treatment with 5-fluorouracil (80%) used in clinical therapy. The reduction of the morphological dimensions in the spheroid cells after Trigno M, was compared with 5-fluorouracil demonstrating the efficacy of the Trigno M compound also in 3D models. Flow cytometric analysis on 3D cells showed a significant increase in the apoptotic cell fraction after Trigno M treatment (44.8%) and a low level of necrotic fraction (6.7%) as compared with control cells. Trigno M and 5-fluorouracil induced the apoptosis in a comparable percentage. Monotherapy with Trigno M in severely immunodeficient mice, carrying colon rectal cancer xenografts, significantly reduced tumor growth. The histopatological analysis of the ectopic tumors showed a lower level of necrosis after Trigno M treatment compared with the control. We conclude that Trigno M is well tolerated by mice, delays colorectal cancer growth in these animals and should be weighed up for integration of the current multi-drug protocols in the treatment of colon carcinoma

Safer_RAIN: A DEM-based hierarchical filling-&-spilling algorithm for pluvial flood hazard assessment and mapping across large urban areas

The increase in frequency and intensity of extreme precipitation events caused by the changing climate (e.g., cloudbursts, rainstorms, heavy rainfall, hail, heavy snow), combined with the high population density and concentration of assets, makes urban areas particularly vulnerable to pluvial flooding. Hence, assessing their vulnerability under current and future climate scenarios is of paramount importance. Detailed hydrologic-hydraulic numerical modeling is resource intensive and therefore scarcely suitable for performing consistent hazard assessments across large urban settlements. Given the steadily increasing availability of LiDAR (Light Detection And Ranging) high-resolution DEMs (Digital Elevation Models), several studies highlighted the potential of fast-processing DEM-based methods, such as the Hierarchical Filling-&-Spilling or Puddle-to-Puddle Dynamic Filling-&-Spilling Algorithms (abbreviated herein as HFSAs). We develop a fast-processing HFSA, named Safer_RAIN, that enables mapping of pluvial flooding in large urban areas by accounting for spatially distributed rainfall input and infiltration processes through a pixel-based Green-Ampt model. We present the first applications of the algorithm to two case studies in Northern Italy. Safer_RAIN output is compared against ground evidence and detailed output from a two-dimensional (2D) hydrologic and hydraulic numerical model (overall index of agreement between Safer_RAIN and 2D benchmark model: sensitivity and specificity up to 71% and 99%, respectively), highlighting potential and limitations of the proposed algorithm for identifying pluvial flood-hazard hotspots across large urban environments