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This paper illustrates the process of design under uncertainty on a practical case study of an offshore wind farm. We document the entire process through selection and quantification of relevant uncertainties, definition of probabilistic limit states, reliability computation algorithms, as well as illustrating the impacts of the analysis through a design utilization study. The brief introduction in this study draws information and summarizes outcomes from the extensive works that took part within the EU H2020 HIPERWIND project. The results from the study show that significant material savings can be achieved by introducing probabilistic design methodologies, and particularly with the help of an integrated modelling approach where the entire structure (turbine, tower & foundation) is considered as a whole.

This article presents a simplified stress–strain relationship for the definition of the mechanical behavior of prestressing strands subjected to chloride-induced corrosion, named SCPS-model (Simplified Model for Corroded Prestressing Strands). The constitutive law adopts the equivalent spring model, that reproduces the overall behavior of a corroded strand by summing the contributions of each wire, assumed as a spring working in parallel to the others. The SCPS-model is designed for the application in the daily engineering practice; to this aim, it is based on a single input parameter that is the maximum penetration depth of the most corroded wire. Following a detailed description of the model formulation and parameters, the article shows the validation of the stress–strain relationship through several comparisons with experimental tensile test outcomes coming from scientific literature. Finally, a statistical analysis of the dimensionless ratio of experimental and analytical results in terms of ultimate corroded strength and strain is carried out to demonstrate the effectiveness of the SCPS-model. Concluding, the accurate and safe side prediction of the residual mechanical behavior of corroded prestressing strands is proposed using the SCPS-model.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the presence of tyrosine kinase BCR-ABL1 fusion protein, which deregulate transcription and mRNA translation. Tyrosine kinase inhibitors (TKIs) are the first-choice treatment. However, resistance to TKIs remains a challenge to cure CML patients. Here, we reveal that the m6A methyltransferase complex METTL3/METTL14 is upregulated in CML patients and that is required for proliferation of primary CML cells and CML cell lines sensitive and resistant to the TKI imatinib. We demonstrate that depletion of METTL3 strongly impairs global translation efficiency. In particular, our data show that METTL3 is crucial for the expression of genes involved in ribosome biogenesis and translation. Specifically, we found that METTL3 directly regulates the level of PES1 protein identified as an oncogene in several tumors. We propose a model in which nuclear METTL3/METTL14 methyltransferase complex modified nascent transcripts whose translation is enhanced by cytoplasmic localization of METTL3, independently from its catalytic activity. In conclusion, our results point to METTL3 as a novel relevant oncogene in CML and as a promising therapeutic target for TKI resistant CML.

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm caused by the presence of tyrosine kinase BCR-ABL1 fusion protein, which deregulate transcription and mRNA translation. Tyrosine kinase inhibitors (TKIs) are the first-choice treatment. However, resistance to TKIs remains a challenge to cure CML patients. Here, we reveal that the m(6)A methyltransferase complex METTL3/METTL14 is upregulated in CML patients and that is required for proliferation of primary CML cells and CML cell lines sensitive and resistant to the TKI imatinib. We demonstrate that depletion of METTL3 strongly impairs global translation efficiency. In particular, our data show that METTL3 is crucial for the expression of genes involved in ribosome biogenesis and translation. Specifically, we found that METTL3 directly regulates the level of PES1 protein identified as an oncogene in several tumors. We propose a model in which nuclear METTL3/METTL14 methyltransferase complex modified nascent transcripts whose translation is enhanced by cytoplasmic localization of METTL3, independently from its catalytic activity. In conclusion, our results point to METTL3 as a novel relevant oncogene in CML and as a promising therapeutic target for TKI resistant CML.

The geometric morphology of pits induced by corrosion has been investigated. To this aim, twenty-four seven-wire strands coming from 10 years old naturally corroded prestressed concrete beams have been analysed. The cross-sections of corroded strands were measured and examined in detail. The morphology of corrosion pits has been recorded by using a structured light 3D scanner and classified in terms of maximum pit depth, longitudinal dimension, and transversal width. Then, a new method for the approximate evaluation of the average pit depth of prestressing strands has been proposed. Finally, the pitting factor of the corroded samples has been calculated.

This study describes two new species, Trinigyrus anthus n. sp. and Trinigyrus carvalhoi n. sp., from gills of Hypostomus spp. from the Upper Paraná River basin, Brazil. Trinigyrus peregrinus is redescribed based on examination of its holotype, paratypes and new material of specimens parasitizing Pterygoplichthys ambrosettii, also from the Upper Paraná River basin, Brazil. New morphological features were included in the diagnosis of the genus, such as the presence of a sclerotized border on the anchor base, and a weakly sclerotized fringe on the base of the male copulatory organ (MCO). Trinigyrus anthus n. sp. differs from other congeners by the shape of the MCO, presenting an enlarged base with sclerotized fringes resembling flower petals. Trinigyrus carvalhoi n. sp. and T. peregrinus are similar but can be differentiated from each other mainly by the sclerotization of the vagina (absent in the new species), and the morphology of the MCO (C-shaped versus one counterclockwise circle, respectively). For the first time, gene sequences of Trinigyrus spp. from Brazil were obtained (partial ribosomal 28S and mitochondrial cytochrome c oxidase I (mtCOI)). The genetic divergences among the new species and T. peregrinus varied from 2 to 3% (6‒18 pb) based on sequences of 28S ribosomal DNA (rDNA), and 6–7% (83‒92 pb) using mtCOI. Phylogenetic analyses based on partial 28S rDNA revealed that Trinigyrus, Heteropriapulus and Unilatus formed a monophyletic and well-supported clade of monogeneans from Neotropical freshwater loricariids, suggesting a closer relationship among these dactylogyrids and their hosts

Traditional Japanese woodworking techniques have been inherited between generations in the past millennia through the Daiku, the master carpenter that teaches apprentices the precise and valuable skills of carpentry through methodical and time-intensive processes. Throughout the 21st Century, with the development of advanced construction methods, coupled with younger generations exhibiting little interest in following the Daiku, this valuable cultural artform is becoming less prevalent in Japanese culture. However, the development of advanced digital tools offers an avenue through which the knowledge and skills of older generations can be both transferred and developed by younger generations. In this context, the paper examines the relationship between traditional Japanese woodworking and advanced computational tools by bringing experts from both disciplines for the design and construction of a Japanese Pagoda, in which the significance of bridging the gap between both domains is highlighted across the design, fabrication and assembly of the project.

INTRODUCTION: No publications were found regarding liquid inoculation in the planting furrow of dry bean, which indicates a demand for investigations to assist the producer in deciding which method of inoculation to adopt. Thus, the aim of this study was to evaluate the viability of liquid inoculation in the planting furrow and determine the best application rate of inoculant, using the dry bean cultivar IAC Alvorada. MATERIALS AND METHODS: A field experiment was conducted in a no-till planting system in the 2014/2015 crop season in a Latossolo Vermelho distrófico in the municipality of Lambari, MG, Brazil. The experimental design was randomized blocks with three replications and eight treatments, involving five application rates of liquid inoculant in the planting furrow (0, 120, 240, 480, and 720 mL ha-1), liquid seed inoculation (40 mL kg-1), and two controls without inoculation: one with N-urea (80 kg ha-1 N, ½ at sowing and ½ in topdressing, between the V3 and V4 stages of the crop cycle) and another without mineral N. The experimental unit (14.4 m2) consisted of six four-meter-length rows, spaced at 0.6 m, and the area effectively used was the four central rows. All the plots received base fertilization of 110 kg ha-1 of P2O5 (simple superphosphate) and 40 kg ha-1 of K2O (potassium chloride), mechanically applied during furrowing. In addition, all levels of inoculation received 20 kg Nurea ha-1, so as to meet the recommendations of Soares et al. (2016). Sowing was manual at the density of 15 seeds per meter and the cultivar used was IAC Alvorada, of semi-upright plant architecture and moderate resistance to anthracnose (Carbonell et al., 2008).

To assess Guillain-Barre syndrome (GBS) incidence we relied on the Italian Network for the study of GBS (ITANG) established in 2010 in 7 Italian regions to analyse the association between influenza vaccination and GBS. Methods: All individuals aged ≥18 years, presenting with clinical manifestations that suggested GBS according to the universally accepted Asbury's diagnostic criteria (1990) were prospectively notified to a centralised database by ITANG neurologists over the period October 1, 2010-September 30, 2011. Through a telephone survey, 9 trained interviewers followed up the cases to diagnosis and then for 1 year since hospital discharge. Validation of case reporting was performed with the support of administrative data in 5 regions. Results: We found 365 cases fulfilling the definition for GBS or one of its variants over 19,846,068 population ≥18 years of age, yielding an annual incidence rate of 1.84 per 100,000 (95% CI 1.65-2.03), 2.30 (95% CI 1.99-2.60) in men and 1.41 (95% CI 1.18-1.64) in women. A highly significant peak of incidence was observed in February 2011 as compared to reference month (September 2011, rate ratio 3.3:1, p < 0.01). Conclusions: In Italy, GBS incidence was among the highest reported in Europe and higher than previously observed in Italian studies.

Background: We reported that 6-month therapy with intravenous immunoglobulin (IVIg) was more frequently effective or tolerated than intravenous methylprednisolone (IVMP) in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We now retrospectively compared the proportion of patients who eventually worsened after discontinuing therapy and the median time to clinical worsening. Methods: By March 2013, data were available from 41 of the 45 patients completing the trial with a median follow-up after therapy discontinuation of 42 months (range 1-60). Three patients withdrew during the original study and one failed to respond to either of the therapies. No patient received a diagnosis alternative to CIDP during the follow-up. Results: Twenty-eight of the 32 patients treated with IVIg (as primary or secondary therapy after failing to respond to IVMP) improved after therapy (87.5%) as compared with 13 of the 24 patients treated with IVMP as primary or secondary therapy (54.2%). After a median follow-up of 42 months (range 1-57), 24 out of 28 patients responsive to IVIg (85.7%) worsened after therapy discontinuation. The same occurred in 10 out of 13 patients (76.9%) responsive to IVMP (p=0.659) after a median follow-up of 43 months (range 7-60). Worsening occurred 1-24 months (median 4.5) after IVIg discontinuation and 1-31 months (median 14) after IVMP discontinuation (p=0.0126). Conclusions: A similarly high proportion of patients treated with IVIg or IVMP eventually relapse after therapy discontinuation but the median time to relapse was significantly longer after IVMP than IVIg. This difference may help to balance the more frequent response to IVIg than to IVMP in patients with CIDP.