Development and significance of tectonic foliations in the Hercynian Belt of NW Spain

[Resumen] En este trabajo se presenta un modelo de distribución y desarrollo de foliaciones en rocas pelíticas y samíticas dentro de un orógeno: el Macizo Herciniano del NW d e España. Estas rocas estuvieron sometidas a una deformación polifásica, con tres fases principales, en condiciones que van desde la transición diagénesis-metamorfismo hasta un metamorfismo de alto grado. Las características de las foliaciones asociadas a las distintas fases de deformaci6n varían progresivamente a medida que lo hace el metamorfismo, existiendo, no obstante, algunos saltos bruscos en dichas características, cuya situaci6n coincide con los límites entre algunas de las grandes zonas en que se divide el orógeno. En todo caso, la foliación tect6nica primaria(Sl) muestra un carácter generalizado, mientras que las otras dos (S2 y S3) presentan una distribución más irregular, apareciendo la S2 en relación con las zonas de cizalla asociadas a grandes cabalgamientos y la S3 controlada por la posición de la anisotropía previa dominante. En la formaci6n de estas foliaciones intervino, en general, de manera muy importante la disolución por presión en las áreas menos metamórficas y la recristalización orientada de filosilicatos en las más metamórficas. El análisis de las relaciones cronológicas entre cristalización metamórfica y desarrollo de foliaciones pone de manifiesto una cierta heterogeneidad espacial en el momento de aparición de los episodios metamórficos en relación con los de deformación. Esta heterogeneidad puede explicarse por las alteraciones en las condiciones P, T que produce el emplazamiento de las grandes unidades tectónicas.[Abstract] A model concerning distribution and development of foliations is presented in this paper, for pelitic and psammitic rocks in the Hercynian Belt ofNW Spain. This rocks have undergone three main deformation phases, in conditions ranging from the iagenesis-metamorphism transition to the high grade metamorphism. The features of the foliations associated to the different phases varie progressively with the metamorphism. Nevertheless, sorne abrupt changes in this features can also be found in sorne of the borders between the main tectonic units. Anyhow, the primary tectonic foliation (Si) is generalized, and the other two (S2 and S3) have a more irregular distribution, related to shear zones associated to main thrusts (S2), or to zones with a favourable possition of the main previous anisotropy (for S3)' The deformation mechanisms opperating in the development of this foliations were, mainly, pressure solution in the zones with low metamorphism, and recrystalization of orientated phyllosillicates in those with the higher metamorphism. The analysis of the chronologic relationships between metamorphic crystalization and development of the foliations in different tectonic units shows sorne differences in the age of the metamorphic episodes in relation with the deformation. These inhomogeneities can be explained by the changes in P, T conditions produced by the emplacement of the main tectonic units

Contribution to Theme A of the Benchmark Workshop: Effect of Concrete Swelling on the Equilibrium and Displacements of an Arch Dam

The Kariba dam is undergoing concrete expansion as a result of an alkali-aggregate reaction. The model adopted to simulate the process is explained in the paper; it is based on the model first proposed by Ulm et al, as later modified by Saouma and Perotti. It has been implemented in the commercial finite element code Abaqus and applied to solve the benchmark problem. The parameters of the model were calibrated using the data recorded up to 1995. The calibrated model was then used for predicting the evolution of the dam up to the present date. Apart from this prediction the paper offers a number of conclusions, such as the fact that the stress level appears to have a major influence on the expansion process; and it presents some suggestions to improve the formulation of the benchmark, such as providing temperature data and widening the locations and conditions of the data employed in the calibratio

Optimised design of foundations for wind towers

Environmental, political, and other considerations are leading to the installation of growing numbers of wind turbines for electricity generation. The present paper concentrates on onshore installations, in which the turbine is placed at the end of a tower founded on the ground. A serious problem with the foundation or its connection with the tower entails a global failure. A worrying percentage of the towers built before 2010 is ill designed, often with obvious manifestations of the design problem. On the other hand the new designs attempt to optimise material quantities and costs while providing an adequate behaviour under the demands imposed. Principia has gathered considerable experience in both the identification and remediation of the problems experienced by older foundations and the optimisation of new designs. The problem is particularly suitable for numerical simulations with Abaqus and the paper provides the necessary concepts and methodological approach for a reliable and satisfactory solution. More specifically, the concrete geometry is meshed with solid elements. Surface elements including rebar layers are embedded. Other parts of the structure as the steel cylinder, welded studs, anchorage bars, etc. are also included. The concrete behaviour is described with the Abaqus concrete damaged plasticity model. Abaqus/Explicit is used because of the strong non-linearities, mainly caused by concrete cracking and crushing. The methodology allows assessing the suitability of the design for ultimate, serviceability and fatigue limit states

Effect of Concrete Swelling on the Equilibrium and Displacements of an Arch Dam

The Kariba dam is undergoing concrete expansion as a result of an alkali-aggregate reaction. The model adopted to simulate the process is explained in the paper; it is based on the model first proposed by Ulm et al, as later modified by Saouma and Perotti. It has been implemented in the commercial finite element code Abaqus and applied to solve the benchmark problem. The parameters of the model were calibrated using the data recorded up to 1995. The calibrated model was then used for predicting the evolution of the dam up to the present date. Apart from this prediction the paper offers a number of conclusions, such as the fact that the stress level appears to have a major influence on the expansion process; and it presents some suggestions to improve the formulation of the benchmark, such as providing temperature data and widening the locations and conditions of the data employed in the calibratio

Simulation of Temperatures and Stresses during Construction of a RCC Dam

Se describen las variaciones de temperaturas y de tensiones durante la construcción de presas de hormigón compactado. The curing of concrete is an exothermic process. The heat of hydration generated induces temperature increases in the concrete, which will disappear in the long term by heat conduction in the concrete mass and thermal exchanges with the environment. The problem is of particularly interest for large concrete masses, as is the case of dams, because the time involved in the heat diffusion process grows with the square of the dimensions and a hotter dam interior implies the possibility of cracking the exposed surfaces of the dam. The Cuira dam, currently being built in Venezuela using roller compacted concrete, is a 134 m high, arch-gravity dam. In support of the design, different strategies were analysed, including various combinations of cooling of the water and the aggregate in order to achieve acceptable results. The calculations were conducted with Abaqus, taking into account all the necessary mechanical and thermal characteristics, as well as the relevant non-linearities. The analyses led to the conclusion that no cooling was required, even taking into account the stress state imposed by an early and rapid filling of the reservoir

Analysis of Combined Bending and Punching Tests of Reinforced Concrete Slabs within IMPACT III Project

The paper reports on a collaborative effort between the Swiss Federal Nuclear Safety Inspectorate (ENSI) and their consultants Principia and Stangenberg. As part of the IMPACT III project, reduced scale impact tests of reinforced concrete structures were carried out. The simulation of test X3 is presented here and the numerical results are compared with those obtained in the test, carried out in August 2013. The general object is to improve the safety of nuclear facilities and, more specifically, to demonstrate the capabilities of current simulation techniques to reproduce the behaviour of a reinforced concrete structure impacted by a soft missile. The missile is a steel tube with a mass of 50 kg and travelling at 140 m/s. The target is a 250 mm thick, 2,1 m by 2,1 m reinforced concrete wall, held in a stiff supporting frame. The reinforcement includes both longitudinal and transverse rebars. Calculations were carried out before and after the test with Abaqus (Principia) and SOFiSTiK (Stangenberg). In the Abaqus simulation the concrete is modelled using solid elements and a damaged plasticity formulation, the rebars with embedded beam elements, and the missile with shell elements. In SOFiSTiK the target is modelled with non-linear, layered shell elements for the reinforcement on both sides; non-linear shear deformations of shell/plate elements are approximately included. The results generally indicate a good agreement between calculations and measurements

Definite and indeterminate nonalcoholic steatohepatitis share similar clinical features and prognosis: A longitudinal study of 1893 biopsy-proven nonalcoholic fatty liver disease subjects

[Background and Aim] Histological score systems may not fully capture the essential nonalcoholic steatohepatitis (NASH) features, which is one of the leading causes of screening failure in clinical trials. We assessed the NASH distribution and its components across the fibrosis stages and their impact on the prognosis and their relationship with the concept of metabolic-associated fatty liver disease (MAFLD).[Methods] Spanish multicenter study including 1893 biopsy-proven nonalcoholic fatty liver disease (NAFLD) patients from HEPAmet registry. NASH was diagnosed by NAS score ≥4 (including steatosis, ballooning and lobular inflammation) and fibrosis by Kleiner score. The presence of MAFLD was determined. Progression to cirrhosis, first episode of decompensated cirrhosis and death were collected during the follow-up (4.7 ± 3.8 years).[Results] Fibrosis was F0 34.3% (649/1893), F1 27% (511/1893), F2 16.5% (312/1893), F3 15% (284/1893) and F4 7.2% (137/1893). NASH diagnosis 51.9% (982/1893), and its individual components (severe steatosis, ballooning and lobular inflammation), increased from F0 (33.6%) to F2 (68.6%), and decreased significantly in F4 patients (51.8%) (P = .0001). More than 70% of non-NASH patients showed some inflammatory activity (ballooning or lobular inflammation), showing a similar MAFLD rate than NASH (96.2% [945/982] vs. 95.2% [535/562]) and significantly higher than nonalcoholic fatty liver (NAFL) subjects (89.1% [311/349]) (P < .0001). Progression to cirrhosis was similar between NASH (9.5% [51/539]) and indeterminate NASH (7.9% [25/316]), and higher than steatosis (5% [14/263]) (logRank 8.417; P = .015). Death and decompensated cirrhosis were similar between these.[Conclusions] The prevalence of steatohepatitis decreased in advanced liver disease. However, most of these patients showed some inflammatory activity histologically and had metabolic disturbances. These findings should be considered in clinical trials whose main aim is to prevent cirrhosis progression and complications, liver transplant and death.This project has been partially funded by the ‘Consejería de Salud de la Junta de Andalucía’ (PI-0075-2014) and the ‘Spanish Ministry of Economy, Innovation and Competition, Instituto de Salud Carlos III’ (PI19/01404, PI16/01842, PI17/00535 and GLD19/00100).Peer reviewe

Dystrophinopathy Phenotypes and Modifying Factors in Exon 45-55 Deletion

Duchenne muscular dystrophy (DMD) exon 45-55 deletion (del45-55) has been postulated as a model that could treat up to 60% of DMD patients, but the associated clinical variability and complications require clarification. We aimed to understand the phenotypes and potential modifying factors of this dystrophinopathy subset. This cross-sectional, multicenter cohort study applied clinical and functional evaluation. Next generation sequencing was employed to identify intronic breakpoints and their impact on the Dp140 promotor, intronic long noncoding RNA, and regulatory splicing sequences. DMD modifiers (SPP1, LTBP4, ACTN3) and concomitant mutations were also assessed. Haplotypes were built using DMD single nucleotide polymorphisms. Dystrophin expression was evaluated via immunostaining, Western blotting, reverse transcription polymerase chain reaction (PCR), and droplet digital PCR in 9 muscle biopsies. The series comprised 57 subjects (23 index) expressing Becker phenotype (28%), isolated cardiopathy (19%), and asymptomatic features (53%). Cognitive impairment occurred in 90% of children. Patients were classified according to 10 distinct index-case breakpoints; 4 of them were recurrent due to founder events. A specific breakpoint (D5) was associated with severity, but no significant effect was appreciated due to the changes in intronic sequences. All biopsies showed dystrophin expression of >67% and traces of alternative del45-57 transcript that were not deemed pathogenically relevant. Only the LTBP4 haplotype appeared associated the presence of cardiopathy among the explored extragenic factors. We confirmed that del45-55 segregates a high proportion of benign phenotypes, severe cases, and isolated cardiac and cognitive presentations. Although some influence of the intronic breakpoint position and the LTBP4 modifier may exist, the pathomechanisms responsible for the phenotypic variability remain largely unresolved. ANN NEUROL 2022;92:793-80

Liver injury in non-alcoholic fatty liver disease is associated with urea cycle enzyme dysregulation

The main aim was to evaluate changes in urea cycle enzymes in NAFLD patients and in two preclinical animal models mimicking this entity. Seventeen liver specimens from NAFLD patients were included for immunohistochemistry and gene expression analyses. Three-hundred-and-eighty-two biopsy-proven NAFLD patients were genotyped for rs1047891, a functional variant located in carbamoyl phosphate synthetase-1 (CPS1) gene. Two preclinical models were employed to analyse CPS1 by immunohistochemistry, a choline deficient high-fat diet model (CDA-HFD) and a high fat diet LDLr knockout model (LDLr −/−). A significant downregulation in mRNA was observed in CPS1 and ornithine transcarbamylase (OTC1) in simple steatosis and NASH-fibrosis patients versus controls. Further, age, obesity (BMI > 30 kg/m), diabetes mellitus and ALT werefound to be risk factors whereas A-allele from CPS1 was a protective factor from liver fibrosis. CPS1 hepatic expression was diminished in parallel with the increase of fibrosis, and its levels reverted up to normality after changing diet in CDA-HFD mice. In conclusion, liver fibrosis and steatosis were associated with a reduction in both gene and protein expression patterns of mitochondrial urea cycle enzymes. A-allele from a variant on CPS1 may protect from fibrosis development. CPS1 expression is restored in a preclinical model when the main trigger of the liver damage disappears.The research leading to these results has received funding from the Consejería de Salud de la Junta de Andalucía under grant agreement PC-0148-2016-0148 and PE-0451-2018 and Instituto de Salud Carlos III under grant agreements CD21/00095, PI16/01842, PI19/01404, PI19/00589, IFI18/00041, FI20/00201, CD18/00126 and EHD18PI04/2021. Rocío Gallego-Durán has received the Andrew K Burroughs Fellowship from European Association for the Study of the Liver (EASL), Aprendizaje de Nuevas Tecnologías fellowship from Asociación Española para el Estudio del Hígado (AEEH) and CIBERehd Grant to support researcher’s mobility

Deep Molecular Characterization of Milder Spinal Muscular Atrophy Patients Carrying the c.859G&gt;C Variant in SMN2

Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by biallelic loss or pathogenic variants in the SMN1 gene. Copy number and modifier intragenic variants in SMN2, an almost identical paralog gene of SMN1, are known to influence the amount of complete SMN proteins. Therefore, SMN2 is considered the main phenotypic modifier of SMA, although genotype-phenotype correlation is not absolute. We present eleven unrelated SMA patients with milder phenotypes carrying the c.859G>C-positive modifier variant in SMN2. All were studied by a specific NGS method to allow a deep characterization of the entire SMN region. Analysis of two homozygous cases for the variant allowed us to identify a specific haplotype, Smn2-859C.1, in association with c.859G>C. Two other cases with the c.859G>C variant in their two SMN2 copies showed a second haplotype, Smn2-859C.2, in cis with Smn2-859C.1, assembling a more complex allele. We also identified a previously unreported variant in intron 2a exclusively linked to the Smn2-859C.1 haplotype (c.154-1141G>A), further suggesting that this region has been ancestrally conserved. The deep molecular characterization of SMN2 in our cohort highlights the importance of testing c.859G>C, as well as accurately assessing the SMN2 region in SMA patients to gain insight into the complex genotype-phenotype correlations and improve prognostic outcomes