This paper describes the theoretical foundation of and explicit algorithms for a novel approach to morphology and anisotropy analysis of complex spatial structure using tensor-valued Minkowski ...functionals, the so-called Minkowski tensors. Minkowski tensors are generalizations of the well-known scalar Minkowski functionals and are explicitly sensitive to anisotropic aspects of morphology, relevant for example for elastic moduli or permeability of microstructured materials. Here we derive explicit linear-time algorithms to compute these tensorial measures for three-dimensional shapes. These apply to representations of any object that can be represented by a triangulation of its bounding surface; their application is illustrated for the polyhedral Voronoi cellular complexes of jammed sphere configurations and for triangulations of a biopolymer fibre network obtained by confocal microscopy. The paper further bridges the substantial notational and conceptual gap between the different but equivalent approaches to scalar or tensorial Minkowski functionals in mathematics and in physics, hence making the mathematical measure theoretic formalism more readily accessible for future application in the physical sciences.
When a granular material such as sand is mixed with a certain amount of liquid, the surface tension of the latter bestows considerable stiffness to the material, which enables, for example, sand ...castles to be sculpted. The geometry of the liquid interface within the granular pile is of extraordinary complexity and strongly varies with the liquid content. Surprisingly, the mechanical properties of the pile are largely independent of the amount of liquid over a wide range. We resolve this puzzle with the help of X-ray microtomography, showing that the remarkable insensitivity of the mechanical properties to the liquid content is due to the particular organization of the liquid in the pile into open structures. For spherical grains, a simple geometric rule is established, which relates the macroscopic properties to the internal liquid morphologies. We present evidence that this concept is also valid for systems with non-spherical grains. Hence, our results provide new insight towards understanding the complex physics of a large variety of wet granular systems including land slides, as well as mixing and agglomeration problems.
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IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
When a granular material such as sand is mixed with a certain amount of liquid, the surface tension of the latter bestows considerable stiffness to the material, which enables, for example, sand ...castles to be sculpted. The geometry of the liquid interface within the granular pile is of extraordinary complexity and strongly varies with the liquid content. Surprisingly, the mechanical properties of the pile are largely independent of the amount of liquid over a wide range. We resolve this puzzle with the help of X-ray microtomography, showing that the remarkable insensitivity of the mechanical properties to the liquid content is due to the particular organization of the liquid in the pile into open structures. For spherical grains, a simple geometric rule is established, which relates the macroscopic properties to the internal liquid morphologies. We present evidence that this concept is also valid for systems with non-spherical grains. Hence, our results provide new insight towards understanding the complex physics of a large variety of wet granular systems including land slides, as well as mixing and agglomeration problems.
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IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Quantitative measures for anisotropic characteristics of spatial structure are needed when relating the morphology of microstructured heterogeneous materials to tensorial physical properties such as ...elasticity, permeability and conductance. Tensor-valued Minkowski functionals, defined in the framework of integral geometry, provide a concise set of descriptors of anisotropic morphology. In this article, we describe the robust computation of these measures for microscopy images and polygonal shapes. We demonstrate their relevance for shape description, their versatility and their robustness by applying them to experimental data sets, specifically microscopy data sets of non-equilibrium stationary Turing patterns and the shapes of ice grains from Antarctic cores.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
G6PC2 encodes a glucose-6-phosphatase (G6Pase) catalytic subunit that modulates the sensitivity of insulin secretion to glucose and thereby regulates fasting blood glucose (FBG). A common ...single-nucleotide polymorphism (SNP) in G6PC2, rs560887 is an important determinant of human FBG variability. This SNP has a subtle effect on G6PC2 RNA splicing, which raises the question as to whether nonsynonymous SNPs with a major impact on G6PC2 stability or enzyme activity might have a broader disease/metabolic impact. Previous attempts to characterize such SNPs were limited by the very low inherent G6Pase activity and expression of G6PC2 protein in islet-derived cell lines. In this study, we describe the use of a plasmid vector that confers high G6PC2 protein expression in islet cells, allowing for a functional analysis of 22 nonsynonymous G6PC2 SNPs, 19 of which alter amino acids that are conserved in mouse G6PC2 and the human and mouse variants of the related G6PC1 isoform. We show that 16 of these SNPs markedly impair G6PC2 protein expression (>50% decrease). These SNPs have variable effects on the stability of human and mouse G6PC1, despite the high sequence homology between these isoforms. Four of the remaining six SNPs impaired G6PC2 enzyme activity. Electronic health record–derived phenotype analyses showed an association between high-impact SNPs and FBG, but not other diseases/metabolites. While homozygous G6pc2 deletion in mice increases the risk of hypoglycemia, these human data reveal no evidence that the beneficial use of partial G6PC2 inhibitors to lower FBG would be associated with unintended negative consequences.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
We conducted a genome-wide association study (GWAS) analysis of diverticular disease (DivD) of intestine within 724,372 individuals and identified 150 independent genome-wide significant DNA ...variants. Integration of the GWAS results with human gut single-cell RNA sequencing data implicated gut myocyte, mesothelial and stromal cells, and enteric neurons and glia in DivD development. Ninety-five genes were prioritized based on multiple lines of evidence, including SLC9A3, a drug target gene of tenapanor used for the treatment of the constipation subtype of irritable bowel syndrome. A DivD polygenic score (PGS) enables effective risk prediction (area under the curve AUC, 0.688; 95% confidence interval CI, 0.645–0.732) and the top 20% PGS was associated with ∼3.6-fold increased DivD risk relative to the remaining population. Our statistical and bioinformatic analyses suggest that the mechanism of DivD is through colon structure, gut motility, gastrointestinal mucus, and ionic homeostasis. Our analyses reinforce the link between gastrointestinal disorders and the enteric nervous system through genetics.
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•Diverticular disease (DivD) GWAS identifies 150 risk variants in ∼724,000 individuals•The derived polygenic score significantly predicts DivD risk with AUC of 0.69•Potential DivD mechanisms: colon structure, gut motility, gastrointestinal mucus, and ionic homeostasis•Prioritized gene for DivD encodes drug target for IBS, a commonly comorbid disorder
Wu et al. investigate the genetic architecture of diverticular disease (DivD) of intestine by integrating the genotype and hospital record data from over 724,000 individuals across multiple biobanks. The authors identify 150 risk variants, and follow-up analyses implicate several cell types, including gut myocytes, mesothelial and stromal cells, and enteric neurons and glia, in disease development. Prioritized genes include a gene encoding therapeutic target for the constipation subtype of irritable bowel syndrome, a commonly comorbid disorder with DivD. Systematic estimation of genetic correlations of DivD with other complex traits highlights some potentially causal and pleiotropic relationships with DivD.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The permanent loss of a hand or limb results in significant challenges. A number of options are available to individuals who must deal with this loss, including reconstructive surgery using a ...person's own tissue to repair the damage or the use of prosthetic devices. We present an update on the most recent addition to the list of options, namely, composite tissue allotransplantation (CTA). In this procedure, tissue to repair the loss is taken from deceased donors who are giving hearts, kidneys, and tissue for transplantation. We report on the world's longest follow-up of CTA of the hand, as well as four other American hand transplant recipients. In very select patient populations, we propose that transplantation is now a clinical option for amputees.
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DOBA, FSPLJ, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The late evolutionary appearance of the benzodiazepine receptor (BZR) allows an experimental approach for evaluation of the qualitative development of its subunits. Photoaffinity labeling of brain ...membranes with 3Hflunitrazepam followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography offers a suitable method for tracing the qualitative evolution of the BZR. A systematic comparison of the subunit patterns in fishes, amphibians, reptiles, birds, and mammals revealed that the subunit of 53K is phylogenetically the oldest photoaffinity labeled subunit; whereas it is the only band present in the lungfish and most amphibians, additional bands are apparent in higher tetrapods. In fishes, the evolution of the BZR subunits leads to the loss of the 53K subunit. KD values are discussed in relation to specific subunit patterns. Possible explanations for the observed variation of the subunits are discussed, with special emphasis placed on the possible evolution by gene duplication and subsequent divergence.
We have constructed a tomato genomic library in the gamma Charon 4 phage vector. The library was screened with a pea cDNA probe encoding a chlorophyll a/b-binding protein (CAB), and several ...recombinant phages containing tomato CAB genes were isolated and characterized by restriction mapping, heteroduplex analysis and nucleotide sequencing. Two phages with overlapping segments of the tomato genome contain a total of four CAB genes, all arranged in tandem. A third phase contains three CAB genes, two arranged in tandem and one in opposite orientation, and an additional, truncated CAB gene. Genetic mapping experiments showed that the four CAb genes on the first two phages belong to a locus, previously designated Cab-1, on chromosome 2. The CAB genes from the third phage belong to the Cab-3 locus on chromosome 3. Complete sequence determination of two CAB genes, one from each locus, and additional sequence determination of about 50% of each of the other five CAB genes showed that each gene within a CAB locus is more similar to other CAB genes in the same locus than it is to the CAB genes from the second locus. Furthermore, the polypeptides encoded by Cab-1 genes diverge significantly from those encoded by Cab-3 genes in the domains of transit peptide and the N terminus of the mature polypeptide but are essentially identical in the rest of the sequence.
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