A homogenised model for flow, transport and sorption in a heterogeneous porous medium

A major challenge in flow through porous media is to better understand the link between pore-scale microstructure and macroscale flow and transport. For idealised microstructures, the mathematical framework of homogenisation theory can be used for this purpose. Here, we consider a two-dimensional microstructure comprising an array of circular obstacles, the size and spacing of which can vary along the length of the porous medium.We use homogenisation via the method of multiple scale to systematically upscale a novel problem that involves cells of varying area to obtain effective continuum equations for macroscale flow and transport. The equations are characterized by the local porosity, an effective local anisotropic flow permeability, and an effective local anisotropic solute diffusivity. These macroscale properties depend non-trivially on both degrees of microstructural geometric freedom (obstacle size and spacing). We take advantage of this dependence to compare scenarios where the same porosity field is constructed with different combinations of obstacle size and spacing. For example, we consider scenarios where the porosity is spatially uniform but the permeability and diffusivity are not. Our results may be useful in the design of filters, or for studying the impact of deformation on transport in soft porous media

Expanding the clinical phenotype of IARS2-related mitochondrial disease.

BACKGROUND: IARS2 encodes a mitochondrial isoleucyl-tRNA synthetase, a highly conserved nuclear-encoded enzyme required for the charging of tRNAs with their cognate amino acid for translation. Recently, pathogenic IARS2 variants have been identified in a number of patients presenting broad clinical phenotypes with autosomal recessive inheritance. These phenotypes range from Leigh and West syndrome to a new syndrome abbreviated CAGSSS that is characterised by cataracts, growth hormone deficiency, sensory neuropathy, sensorineural hearing loss, and skeletal dysplasia, as well as cataract with no additional anomalies. METHODS: Genomic DNA from Iranian probands from two families with consanguineous parental background and overlapping CAGSSS features were subjected to exome sequencing and bioinformatics analysis. RESULTS: Exome sequencing and data analysis revealed a novel homozygous missense variant (c.2625C > T, p.Pro909Ser, NM_018060.3) within a 14.3 Mb run of homozygosity in proband 1 and a novel homozygous missense variant (c.2282A > G, p.His761Arg) residing in an ~ 8 Mb region of homozygosity in a proband of the second family. Patient-derived fibroblasts from proband 1 showed normal respiratory chain enzyme activity, as well as unchanged oxidative phosphorylation protein subunits and IARS2 levels. Homology modelling of the known and novel amino acid residue substitutions in IARS2 provided insight into the possible consequence of these variants on function and structure of the protein. CONCLUSIONS: This study further expands the phenotypic spectrum of IARS2 pathogenic variants to include two patients (patients 2 and 3) with cataract and skeletal dysplasia and no other features of CAGSSS to the possible presentation of the defects in IARS2. Additionally, this study suggests that adult patients with CAGSSS may manifest central adrenal insufficiency and type II esophageal achalasia and proposes that a variable sensorineural hearing loss onset, proportionate short stature, polyneuropathy, and mild dysmorphic features are possible, as seen in patient 1. Our findings support that even though biallelic IARS2 pathogenic variants can result in a distinctive, clinically recognisable phenotype in humans, it can also show a wide range of clinical presentation from severe pediatric neurological disorders of Leigh and West syndrome to both non-syndromic cataract and cataract accompanied by skeletal dysplasia

A homogenised model for flow, transport and sorption in a heterogeneous porous medium

A major challenge in flow through porous media is to better understand the link between pore-scale microstructure and macroscale flow and transport. For idealised microstructures, the mathematical framework of homogenisation theory can be used for this purpose. Here, we consider a two-dimensional microstructure comprising an array of circular obstacles, the size and spacing of which can vary along the length of the porous medium.We use homogenisation via the method of multiple scale to systematically upscale a novel problem that involves cells of varying area to obtain effective continuum equations for macroscale flow and transport. The equations are characterized by the local porosity, an effective local anisotropic flow permeability, and an effective local anisotropic solute diffusivity. These macroscale properties depend non-trivially on both degrees of microstructural geometric freedom (obstacle size and spacing). We take advantage of this dependence to compare scenarios where the same porosity field is constructed with different combinations of obstacle size and spacing. For example, we consider scenarios where the porosity is spatially uniform but the permeability and diffusivity are not. Our results may be useful in the design of filters, or for studying the impact of deformation on transport in soft porous media

The radial expansion of the Diego blood group system polymorphisms in Asia: mark of co-migration with the Mongol conquests

International audienceRed cell polymorphisms can provide evidence of human migration and adaptation patterns. In Eurasia, the distribution of Diego blood group system polymorphisms remains unaddressed. To shed light on the dispersal of the Di a antigen, we performed analyses of correlations between the frequencies of DI*01 allele, C2-M217 and C2-M401 Y-chromosome haplotypes ascribed as being of Mongolian-origin and language affiliations, in 75 Eurasian populations including DI*01 frequency data from the HGDP-CEPH panel. We revealed that DI*01 reaches its highest frequency in Mongolia, Turkmenistan and Kyrgyzstan, expanding southward and westward across Asia with Altaic-speaking nomadic carriers of C2-M217, and even more precisely C2-M401, from their homeland presumably in Mongolia, between the third century BCE and the thirteenth century CE. The present study has highlighted the gene-culture co-migration with the demographic movements that occurred during the past two millennia in Central and East Asia. Additionally, this work contributes to a better understanding of the distribution of immunogenic erythrocyte polymorphisms with a view to improve transfusion safety