Numerical treatment of the loss of hyperbolicity of the two-layer SWS.

In this work, a characterization of the hyperbolicity region for the two layer shallow-water system is proposed and checked. Next, some path-conservative finite volume schemes (see [11]) that can be used even if the system is not hyperbolic are presented, but they are not in general L2 linearly stable in that case. Then, we introduce a simple but efficient strategy to enforce the hyperbolicity of the two-layer shallow-water system consisting in adding to the system an extra amount of friction at every cell in which complex eigenvalues are detected at a given time step. The implementation is performed by a predictor/corrector strategy: first a numerical scheme is applied to the unmodified two-layer system, regardless of the hyperbolic character of the system. Next, we check if the predicted cell averages are in the hyperbolic region or not. If not, the mass-fluxes are corrected by adding a quadratic friction law between layers whose coefficient is computed so that the corrected cell average is as near as possible of the boundary of the hyperbolicity region. Finally, some numerical test have been performed to assess the efficiency of the proposed strateg

Well-balanced finite volume schemes for 2D non-homogeneous hyperbolic systems. Application to the dam-break of Aznalcóllar.

In this paper, we introduce a class of well-balanced finite volume schemes for 2D non-homogeneous hyperbolic systems. We extend the derivation of standard finite volume solvers for homogeneous systems to non-homogeneous ones using the method of lines. We study conservation and some well-balanced properties of the numerical scheme. We apply our solvers to shallow water equations: we prove that these exactly compute the water at rest solutions. We also perform some numerical tests, by comparing with 1D solutions, simulating the formation of a hydraulic drop and a hydraulic jump, and studying a real dam break: Aznalcóllar, an ecological disaster happened in the province of Seville, Spain in 1998

Efficient GPU implementation of a two waves TVD-WAF method for the two-dimensional one layer Shallow Water system on structured meshes.

The numerical solutions of shallow water equations are useful for applications related to geophysical flows that usually take place in large computational domains and could require real time calculation. Therefore, parallel versions of accurate and efficient numerical solvers for high performance platforms are needed to be able to deal with these simulation scenarios in reasonable times. In this paper we present an efficient CUDA implementation of a first and second order HLL methods and a two-waves TVD-WAF one. We propose to write all these methods under a common framework, such as, their CUDA implementations share the same structure. In particular, the reformulation of TVD-WAF numerical flux and the improved definition of the flux limiter allows us to obtain a more robust solver in situations like wet/dry fronts. Finally, some numerical tests are presented showing that the TVD-WAF method is slightly slower that the first order HLL method and two times faster than the second order HLL method, but it provides numerical results almost as accurate as the second order HLL scheme

Epidemiological, Clinical and Genetic Study of Hypophosphatasia in A Spanish Population: Identification of Two Novel Mutations in The Alpl Gene

Hypophosphatasia (HPP) is a genetic disease caused by one or several mutations in ALPL gene encoding the tissue-nonspecific alkaline phosphatase affecting the mineralization process. Due to its low prevalence and lack of recognition, this metabolic disorder is generally confused with other more frequent bone disorders. An assessment of serum total alkaline phosphatase (ALP) levels was performed in 78,590 subjects. Pyridoxal-5′-phosphate (PLP) concentrations were determined and ALPL gene was sequenced in patients potentially affected by HPP. Functional validation of the novel mutations found was performed using a cell-based assay. Our results showed persistently low serum ALP levels in 0.12% of subjects. Among the studied subjects, 40% presented with HPP-related symptoms. Nine of them (~28%) had a history of fractures, 5 (~16%) subjects showed chondrocalcinosis and 4 (~13%) subjects presented with dental abnormalities. Eleven subjects showed increased PLP concentrations. Seven of them showed ALPL gene mutations (2 of the mutations corresponded to novel genetic variants). In summary, we identified two novel ALPL gene mutations associated with adult HPP. Using this protocol, almost half of the studied patients were diagnosed with HPP. Based on these results, the estimated prevalence of mild HPP in Spain could be up to double than previously reported.Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (with support from NIH P41-GM103311)grants from Alexion and FEIOMM, by Instituto de Salud Carlos III (grants PI18-00803 and PI18-01235)co-funding from FEDER and by Junta de Andalucía (grant PI-0207-2016)GM-N is supported by the predoctoral program from Instituto de Salud Carlos III (FI17/00178) and by the Research Initiation Grants for Official Master Students program from the University of Granada (2017)PJR is a Ramon y Cajal Researcher from the MINECO (RYC-2015-18383) at GENyO and University of Granada

Mild hypophosphatasia may be twice as prevalent as previously estimated: an effective clinical algorithm to detect undiagnosed cases

Objectives: Since the prevalence of hypophosphatasia (HPP), a rare genetic disease, seems to be underestimated in clinical practice, in this study, a new diagnostic algorithm to identify missed cases of HPP was developed and implemented. Methods: Analytical determinations recorded in the Clinical Analysis Unit of the Hospital Universitario Clínico San Cecilio in the period June 2018 – December 2020 were reviewed. A new clinical algorithm to detect HPP-misdiagnosed cases was used including the following steps: confirmation of persistent hypophosphatasemia, exclusion of secondary causes of hypophosphatasemia, determination of serum pyridoxal- 5′-phosphate (PLP) and genetic study of ALPL gene. Results: Twenty-four subjects were selected to participate in the study and genetic testing was carried out in 20 of them following clinical algorithm criteria. Eighty percent of patients was misdiagnosed with HPP following the current standard clinical practice. Extrapolating these results to the current Spanish population means that there could be up to 27,177 cases of undiagnosed HPP in Spain. In addition, we found a substantial proportion of HPP patients affected by other comorbidities, such as autoimmune diseases (∼40 %). Conclusions: This new algorithm was effective in detecting previously undiagnosed cases ofHPP, which appears to be twice as prevalent as previously estimated for the European population. In the near future, our algorithm could be globally applied routinely in clinical practice to minimize the underdiagnosis of HPP. Additionally, some relevant findings, such as the high prevalence of autoimmune diseases in HPP-affected patients, should be investigated to better characterize this disorder.Instituto de Salud Carlos III grants PI21-01069 co-funded by the European Regional Development Fund (FEDER) and by Junta de Andalucía grant PI-0268-2019Operational Programme for Youth Employment of the Junta de Andalucía with Ref: POEJ_04/2022-12Instituto de Salud Carlos III with co-funding by FEDER (CD20/00022)(FI19/00118 and CM21/00221) from Instituto de Salud CarlosPostdoctoral fellowship from the Junta de Andalucía (RH-0141-2020

Systemic effects of hypophosphatasia characterization of two novel variants in the ALPL gene

IntroductionHypophosphatasia (HPP) is an inborn metabolic error caused by mutations in the ALPL gene encoding tissue non-specific alkaline phosphatase (TNSALP) and leading to decreased alkaline phosphatase (ALP) activity. Although the main characteristic of this disease is bone involvement, it presents a great genetic and clinical variability, which makes it a systemic disease.MethodsPatients were recruited based on biochemical assessments. Diagnosis was made by measuring serum ALP and pyridoxal 5-phosphate levels and finally by Sanger sequencing of the ALPL gene from peripheral blood mononuclear cells. Characterization of the new variants was performed by transfection of the variants into HEK293T cells, where ALP activity and cellular localization were measured by flow cytometry. The dominant negative effect was analyzed by co-transfection of each variant with the wild-type gene, measuring ALP activity and analyzing cellular localization by flow cytometry.ResultsTwo previously undescribed variants were found in the ALPL gene: leucine 6 to serine missense mutation (c.17T>C, L6S) affecting the signal peptide and threonine 167 deletion (c.498_500delCAC, T167del) affecting the vicinity of the active site. These mutations lead mainly to non-pathognomonic symptoms of HPP. Structural prediction and modeling tools indicated the affected residues as critical residues with important roles in protein structure and function. In vitro results demonstrated low TNSALP activity and a dominant negative effect in both mutations. The results of the characterization of these variants suggest that the pleiotropic role of TNSALP could be involved in the systemic effects observed in these patients highlighting digestive and autoimmune disorders associated with TNSALP dysfunction.ConclusionsThe two new mutations have been classified as pathogenic. At the clinical level, this study suggests that both mutations not only lead to pathognomonic symptoms of the disease, but may also play a role at the systemic level

Deslizamientos submarinos y tsunamis en el Mar de Alborán. Un ejemplo de modelización numérica

Los componentes principales de este libro son: a) conocer y estudiar determinados fenómenos naturales de consecuencias catastróficas, como los tsunamis, y b) identificar los útiles científicos para representar estos fenómenos. Por ello, es necesario disponer de un profundo conocimiento del fondo marino donde se produce el fenómeno, conocimiento que proviene del análisis de datos geológicos y geofísicos, y por otro lado, es encesario hacer uso de la potencialidad de los modelos matemáticos que permiten realizar simulaciones numéricas precisas. El libro presenta los resultados de la simulación numérica de un tsunami generado en la cuenca del Mar de Alborán y su propagación e interacción con la morfología submarina de dicho área geográfica.Versión del edito

The EU Center of Excellence for Exascale in Solid Earth (ChEESE): Implementation, results, and roadmap for the second phase

publishedVersio