Evaluation of current trends of climatic actions in europe based on observations and regional reanalysis

Since extreme values of climatic actions are commonly derived assuming the climate being stationary over time, engineering structures and infrastructures are designed considering design actions derived under this assumption. Owing to the increased relevance of the expected climate change effects and the correlated variations of climate actions extremes, ad hoc strategies for future adaption of design loads are needed. Moreover, as current European maps for climatic actions are generally based on observations collected more than 20 years ago, they should be updated. By a suitable elaboration of the projections of future climate changes, the evolution over time of climatic actions can be assessed; this basic and crucial information allows us to facilitate future adaptations of climatic load maps, thus improving the climate resilience of structures and infrastructures. In this paper, current trends of climatic actions in Europe, daily maximum and minimum temperatures, daily precipitation, and ground snow loads, are investigated based on available gridded datasets of observations (E-OBS) and regional reanalysis (Uncertainties in Ensembles of Regional Re-Analyses, UERRA), to assess their suitability to be used in the elaboration of maps for climatic actions. The results indicate that the E-OBS gridded datasets reproduce trends in extreme temperatures and precipitation well in the investigated regions, while reanalysis data, which include snow water equivalent, show biases in the assessment of ground snow load modifications over the years in comparison with measurements. As far as climate change effects are concerned, trends of variation of climatic actions are estimated considering subsequent time windows, 40 years in duration, covering the period 1950–2020. Results, in terms of factors of change, are critically discussed, also in comparison with the elaborations of reliable datasets of real observations, considering a case study covering Germany and Switzerland

Influence of reinforcing steel corrosion on life cycle reliability assessment of existing R.C. Buildings

Time-dependent reliability assessment is a crucial aspect of the decision process for rehabilitation of existing reinforced concrete structures. Since the assessment strongly depends on degradation of materials with time, the paper focuses on the influence of corrosion in reinforcing steel on time-reliability curves of relevant reinforced concrete (r.c.) structures, built in Italy in the 1960s, belonging to different building categories. To realistically represent the probability distribution functions (pdf s) of the relevant properties of reinforcing steel and concrete commonly adopted in the 1960s, stochastic models for steel yielding and concrete compressive strength have been derived, by means of a suitable cluster analysis, from secondary databases of test results gathered at that time in Italy on concrete and steel rebar specimens. This cluster analysis, based on Gaussian mixture models, provides a powerful tool to "objectively" extract material classes and associated probability density functions from databases of experimental test results. In the study, different degradation conditions and several reinforcing steel and concrete classes are considered, also aiming to scrutinize their influence on the time-dependent reliability curves. Finally, to stress the significance of the study, the time-dependent reliability curves so obtained are critically examined and discussed also in comparison with the target reliability levels currently adopted in the Eurocodes

Probabilistic assessment of roof snow load and the calibration of shape coefficients in the eurocodes

In modern structural codes, the reference value of the snow load on roofs is commonly given as the product of the characteristic value of the ground snow load at the construction site multiplied by the shape coefficient. The shape coefficient is a conversion factor which depends on the roof geometry, its wind exposure, and its thermal properties. In the Eurocodes, the characteristic roof snow load is either defined as the value corresponding to an annual probability of exceedance of 0.02 or as a nominal value. In this paper, an improved methodology to evaluate the roof snow load characterized by a given probability of exceedance (e.g., p=0.02 in one year) is presented based on appropriate probability density functions for ground snow loads and shape coefficients, duly taking into account the influence of the roof’s geometry and its exposure to wind. In that context, the curves for the design values of the shape coefficients are provided as a function of the coefficient of variation (COVg) of the yearly maxima of the snow load on the ground expected at a given site, considering three relevant wind exposure conditions: sheltered or non-exposed, semisheltered or normal, and windswept or exposed. The design shape coefficients for flat and pitched roofs, obtained considering roof snow load measurements collected in Europe during the European Snow Load Research Project (ESLRP) and in Norway, are finally compared with the roof snow load provisions given in the relevant existing Eurocode EN1991-1-3: 2003 and in the new version being developed (prEN1991-1-3: 2020) for the “second generation” of the Eurocodes

Sustainable Concrete with Recycled Aggregates: experiences and perspective

The recycling of concrete construction and demolition wastes to obtain coarse recycled aggregates for structural concrete production represents an interesting strategy fostering circular economy in the construction sector. In this work, the effects of parent concretes on coarse recycled aggregates and on new structural concretes produced with different replacement percentages of recycled aggregates have been investigated. The quality of parent concrete seems not directly related to the mechanical properties of the concrete prepared with recycled aggregates, while the mix design plays a key role. In addition, tests on concrete specimens (i.e. plinths) have been carried out to demonstrate the feasibility of structural elements with recycled aggregates concrete. In the manuscript we present an overview of these results, highlighting pros and cons of using concrete with recycled aggregates for future developments of the concrete construction market, also stressing the influence of climate change

Bayesian methodology for probabilistic description of mechanical parameters of masonry walls

In consideration of the high vulnerability of the built environment, the assessment of seismic behavior of existing masonry buildings is a key topic in view of their retrofitting and reuse. Because masonry's behavior depends on complex nonhomogeneous, anisotropic, asymmetric, and nonlinear properties, the definition of suitable mechanical models is still a critical issue, especially for stone masonry. Structural analyses of existing masonry buildings in seismic-prone areas are thus significantly influenced by the adopted mechanical models and assumptions about their relevant masonry properties, which are characterized by large uncertainty. In this study, a procedure for the definition of masonry classes and probability density functions of relevant mechanical parameters, such as elastic modulus and shear modulus, is proposed. The general procedure is illustrated referring to a significant number of in situ double-flat-jack test results on stone masonry obtained by the authors during an ad hoc experimental campaign. Finally, combining information on masonry quality obtained by visual inspection with results of in situ tests, a Bayesian methodology is proposed for the updating of masonry mechanical parameters, thereby providing the basis for a more refined probabilistic assessment of the seismic risk index. DOI: 10.1061/AJRUA6.0001110. This work is made available under the terms of the Creative Commons Attribution 4.0 International license, https://creativecommons.org/licenses/by/4.0/

APOPTOSIS, OXIDATIVE STRESS AND NEUROLOGICAL DISEASE

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CCDC78: Unveiling the Function of a Novel Gene Associated with Hereditary Myopathy

CCDC78 was identified as a novel candidate gene for autosomal dominant centronuclear myopathy-4 (CNM4) approximately ten years ago. However, to date, only one family has been described, and the function of CCDC78 remains unclear. Here, we analyze for the first time a family harboring a CCDC78 nonsense mutation to better understand the role of CCDC78 in muscle. Methods: We conducted a comprehensive histopathological analysis on muscle biopsies, including immunofluorescent assays to detect multiple sarcoplasmic proteins. We examined CCDC78 transcripts and protein using WB in CCDC78-mutated muscle tissue; these analyses were also performed on muscle, lymphocytes, and fibroblasts from healthy subjects. Subsequently, we conducted RT-qPCR and transcriptome profiling through RNA-seq to evaluate changes in gene expression associated with CCDC78 dysfunction in muscle. Lastly, coimmunoprecipitation (Co-Ip) assays and mass spectrometry (LC-MS/MS) studies were carried out on extracted muscle proteins from both healthy and mutated subjects. Results: The histopathological features in muscle showed novel histological hallmarks, which included areas of dilated and swollen sarcoplasmic reticulum (SR). We provided evidence of nonsense-mediated mRNA decay (NMD), identified the presence of novel CCDC78 transcripts in muscle and lymphocytes, and identified 1035 muscular differentially expressed genes, including several involved in the SR. Through the Co-Ip assays and LC-MS/MS studies, we demonstrated that CCDC78 interacts with two key SR proteins: SERCA1 and CASQ1. We also observed interactions with MYH1, ACTN2, and ACTA1. Conclusions: Our findings provide insight, for the first time, into the interactors and possible role of CCDC78 in skeletal muscle, locating the protein in the SR. Furthermore, our data expand on the phenotype previously associated with CCDC78 mutations, indicating potential histopathological hallmarks of the disease in human muscle. Based on our data, we can consider CCDC78 as the causative gene for CNM4

A proposed index of myocardial staining for vein of Marshall ethanol infusion: an Italian single-center experience.

Background: Mitral isthmus (MI) conduction block is a fundamental step in anatomical approach treatment for persistent atrial fibrillation (PeAF). However, MI block is hardly achievable with endocardial ablation only. Retrograde ethanol infusion (EI) into the vein of Marshall (VOM) facilitates MI block. Fluorographic myocardial staining (MS) during VOM-EI could be helpful in predicting procedural alcoholization outcome even if its role is qualitatively assessed in the routine. The aim was to quantitatively assess MS during VOM-EI and to evaluate its association with MI block achievement. Methods: Consecutive patients undergoing catheter ablation for PeAF at Fondazione Toscana Gabriele Monasterio (Pisa, Italy) from February 2022 to May 2023 were considered. Patients with identifiable VOM were included. A proposed index of MS (MSI) was retrospectively calculated in each included patient. Correlation of MSI with low-voltage zones (LVZ) extension after VOM-EI and its association with MI block achievement were assessed. Results: In total, 42 patients out of 49 (85.8%) had an identifiable VOM. MI block was successfully achieved in 35 patients out of 42 (83.3%). MSI was significantly associated with the occurrence of MI block (OR 1.24 (1.03-1.48); p = 0.022). A higher MSI resulted in reduced ablation time (p = 0.014) and reduced radiofrequency applications (p = 0.002) to obtain MI block. MSI was also associated with MI block obtained by endocardial ablation only (OR 1.07 (1.02-1.13); p = 0.002). MSI was highly correlated with newly formed LVZ extension (r = 0.776; p = 0.001). Conclusions: In our study cohort, optimal MSI predicts MI block and facilitates its achievement with endocardial ablation only

Intra-islet insulin synthesis defects are associated with endoplasmic reticulum stress and loss of beta cell identity in human diabetes

Aims/hypothesis: Endoplasmic reticulum (ER) stress and beta cell dedifferentiation both play leading roles in impaired insulin secretion in overt type 2 diabetes. Whether and how these factors are related in the natural history of the disease remains, however, unclear. Methods: In this study, we analysed pancreas biopsies from a cohort of metabolically characterised living donors to identify defects in in situ insulin synthesis and intra-islet expression of ER stress and beta cell phenotype markers. Results: We provide evidence that in situ altered insulin processing is closely connected to in vivo worsening of beta cell function. Further, activation of ER stress genes reflects the alteration of insulin processing in situ. Using a combination of 17 different markers, we characterised individual pancreatic islets from normal glucose tolerant, impaired glucose tolerant and type 2 diabetic participants and reconstructed disease progression. Conclusions/interpretation: Our study suggests that increased beta cell workload is accompanied by a progressive increase in ER stress with defects in insulin synthesis and loss of beta cell identity. Graphical abstract: [Figure not available: see fulltext.