Spatial Quality Evaluation of Pedestrian Streets

This paper presents an assessment of the spatial quality of a pedestrian street located in downtown Bauru, S~o Paulo State, Brazil, from the application of some urban sustainability indicators. Multi-method was used to evaluate the thermal comfort quality of users, urban accessibility and preservation of architectural heritage. The results show that the sustainability indicators, apart from being effective tools in identifying problems, can assist local managers in decision making, planning and monitoring of pedestrian public space. These indicators contribute to a broad diagnosis of the pedestrian street and also the formulation of programs, projects and municipal policies, aimed at providing a better life quality for pedestrians.     

Deterministic model to evaluate the impact of lactational treatment of subclinical mastitis due to coagulase-negative staphylococci

Coagulase-negative staphylococci (CNS) are the most frequently isolated bacteria from milk samples in several studies worldwide. Despite their relative frequency, specific measures aiming at their control are not well established. One possible measure to include in a control programme is lactational antimicrobial treatment. The decision to perform such treatment, as well as other actions on farm, should be based on the likelihood of financial return. A deterministic model was used to evaluate whether performing an antimicrobial treatment during the lactation for quarters infected with CNS was financially justifiable. Input variables for the impact of CNS on udder health were based on a previous study by the same authors and on available literature on the subject. Prices included in the model were based on 2009/2010 conditions in Portugal. The average result per antimicrobial treated quarter was a net loss of ?8·74. Performing a sensitivity analysis to evaluate how systematic variation of the input variables of the model would lead to outcome changes showed that variation in input variables nearly always led to a negative outcome, with the greatest variation in losses observed for variation in the length of treatment and milk withdrawal period (-?6·26 to -?8·49). The situations in which a net benefit was to be expected included the bulk tank somatic cell count decreasing to a level corresponding to a premium payment or to penalties being avoided, and the prevention of transmission of CNS in the milking parlour when the possibility of transmission was at its highest level. For most situations, lactational treatment of CNS subclinical mastitis was not financially justifiable.     

Stearoyl CoA Desaturase-1 Silencing in Glioblastoma Cells: Phospholipid Remodeling and Cytotoxicity Enhanced upon Autophagy Inhibition

Modulation of lipid metabolism is a well-established cancer hallmark, and SCD1 has been recognized as a key enzyme in promoting cancer cell growth, including in glioblastoma (GBM), the deadliest brain tumor and a paradigm of cancer resistance. The central goal of this work was to identify, by MS, the phospholipidome alterations resulting from the silencing of SCD1 in human GBM cells, in order to implement an innovative therapy to fight GBM cell resistance. With this purpose, RNAi technology was employed, and low serum-containing medium was used to mimic nutrient deficiency conditions, at which SCD1 is overexpressed. Besides the expected increase in the saturated to unsaturated fatty acid ratio in SCD1 silenced-GBM cells, a striking increase in polyunsaturated chains, particularly in phosphatidylethanolamine and cardiolipin species, was noticed and tentatively correlated with an increase in autophagy (evidenced by the increase in LC3BII/I ratio). The contribution of autophagy to mitigate the impact of SCD1 silencing on GBM cell viability and growth, whose modest inhibition could be correlated with the maintenance of energetically associated mitochondria, was evidenced by using autophagy inhibitors. In conclusion, SCD1 silencing could constitute an important tool to halt GBM resistance to the available treatments, especially when coupled with a mitochondria disrupter chemotherapeutic.     

IL-33 and the Cytokine Storm in COVID-19: From a Potential Immunological Relationship towards Precision Medicine

Coronavirus SARS-CoV-2 has represented, and still represents, a real challenge from a clinical, diagnostic and therapeutic point of view. During acute infection, the increased levels of pro-inflammatory cytokines, which are involved in the pathology of disease and the development of SARS-CoV-2-induced acute respiratory disease syndrome, the life-threatening form of this infection, are correlated with patient survival and disease severity. IL-33, a key cytokine involved in both innate and adaptive immune responses in mucosal organs, can increase airway inflammation, mucus secretion and Th2 cytokine synthesis in the lungs, following respiratory infections. Similar to cases of exposure to known respiratory virus infections, exposure to SARS-CoV-2 induces the expression of IL-33, correlating with T-cell activation and lung disease severity. In this work, we analyse current evidence regarding the immunological role of IL-33 in patients affected by COVID-19, to evaluate not only the clinical impact correlated to its production but also to identify possible future immunological therapies that can block the most expressed inflammatory molecules, preventing worsening of the disease and saving patient lives.     

Unhealthy Diets Induce Distinct and Regional Effects on Intestinal Inflammatory Signalling Pathways and Long-Lasting Metabolic Dysfunction in Rats

The intestinal epithelium is a principal site for environmental agents’ detection. Several inflammation- and stress-related signalling pathways have been identified as key players in these processes. However, it is still unclear how the chronic intake of inadequate nutrients triggers inflammatory signalling pathways in different intestinal regions. We aimed to evaluate the impact of unhealthy dietary patterns, starting at a younger age, and the association with metabolic dysfunction, intestinal inflammatory response, and obesity in adulthood. A rat model was used to evaluate the effects of the consumption of sugary beverages (HSD) and a Western diet (WD), composed of ultra-processed foods. Both diets showed a positive correlation with adiposity index, but a positive correlation was found between the HSD diet and the levels of blood glucose and triglycerides, whereas the WD diet correlated positively with triglyceride levels. Moreover, a distinct inflammatory response was associated with either the WD or HSD diets. The WD induced an increase in TLR2, TLR4, and nuclear factor-kappa B (NF-κB) intestinal gene expression, with higher levels in the colon and overexpression of the inducible nitric oxide synthase. In turn, the HSD diet induced activation of the TLR2-mediated NF-κB signalling pathway in the small intestine. Altogether, these findings support the concept that early intake of unhealthy foods and nutrients are a main exogenous signal for disturbances of intestinal immune mechanisms and in a region-specific manner, ultimately leading to obesity-related disorders in later life.     

The immobilisation of enzymes on titanium-activated inorganic supports

Methods are described for the immobilisation of enzymes on inorganic supports activated by the surface deposition of an imperfectly crystallised film of TiO₂. The stability of the preparations is shown to be strongly dependent on the integrity of the support-TiO₂ link which is in turn dependent on the pretreatment of the solid support. The enzyme may be linked to the activated support using 5-aminosalicylic acid (with or without diazotisation), tannic acid or stannous chloride, or by direct contact. These preparations are shown to have activities and operational stabilities superior to those of a preparation made using the silane-glutaraldehyde method on the same glass support.     

Optimal cross-section and configuration design of elastic-plastic structures subject to dynamic cyclic loading

This paper shows an optimal design problem with continuum variational formulation, applied to nonlinear elasticplastic structures subject to dynamic loading. The total Lagrangian procedure is used to describe the response of the structure. The direct differentiation method is used to obtain the sensitivities of the structural response that are needed to solve the optimization problem. Since unloading and reloading of the structure are allowed, the structural response is path-dependent and an additional step is needed to integrate the constitutive equations. It can be shown, consequently, that design sensitivity analysis is also path-dependent. A finite element method with implicit time integration is used to discretize the state and sensitivity equations.A mathematical programming approach is used for the optimization process. Numerical applications are performed on a 3-D truss structure, where cross-sectional areas and nodal point coordinates are treated as design variables. Optimal designs have been obtained and compared by using two different strategies: a twolevel strategy where the levels are defined according to the type of design variables, cross sectional areas or node coordinates, and optimizing simultaneously with respect to both types of design variables. Comparisons have also been made between optimal designs obtained by considering or not considering the inertial term of the structural equilibrium.     

Equivariant adaptive source separation

Source separation consists of recovering a set of independent signals when only mixtures with unknown coefficients are observed. This paper introduces a class of adaptive algorithms for source separation that implements an adaptive version of equivariant estimation and is henceforth called equivariant adaptive separation via independence (EASI). The EASI algorithms are based on the idea of serial updating. This specific form of matrix updates systematically yields algorithms with a simple structure for both real and complex mixtures. Most importantly, the performance of an EASI algorithm does not depend on the mixing matrix. In particular, convergence rates, stability conditions, and interference rejection levels depend only on the (normalized) distributions of the source signals. Closed-form expressions of these quantities are given via an asymptotic performance analysis. The theme of equivariance is stressed throughout the paper. The source separation problem has an underlying multiplicative structure. The parameter space forms a (matrix) multiplicative group. We explore the (favorable) consequences of this fact on implementation, performance, and optimization of EASI algorithms