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In this article, we consider a phase field model with different densities and viscosities for the coupled two-phase porous media flow and two-phase free flow, as well as the corresponding numerical simulation. This model consists of three parts: a Cahn–Hilliard–Darcy system with different densities/viscosities describing the porous media flow in matrix, a Cahn–Hilliard–Navier–Stokes system with different densities/viscosities describing the free fluid in conduit, and seven interface conditions coupling the flows in the matrix and the conduit. Based on the separate Cahn–Hilliard equations in the porous media region and the free flow region, a weak formulation is proposed to incorporate the two-phase systems of the two regions and the seven interface conditions between them, and the corresponding energy law is proved for the model. A fully decoupled numerical scheme, including the novel decoupling of the Cahn–Hilliard equations through the four phase interface conditions, is developed to solve this coupled nonlinear phase field model. An energy-law preservation is analyzed for the temporal semi-discretization scheme. Furthermore, a fully discretized Galerkin finite element method is proposed. Six numerical examples are provided to demonstrate the accuracy, discrete energy law, and applicability of the proposed fully decoupled scheme. 

Abstract There is a growing recognition that responding to climate change necessitates urban adaptation. We sketch a transdisciplinary research effort, arguing that actionable research on urban adaptation needs to recognize the nature of cities as social networks embedded in physical space. Given the pace, scale and socioeconomic outcomes of urbanization in the Global South, the specificities and history of its cities must be central to the study of how well-known agglomeration effects can facilitate adaptation. The proposed effort calls for the co-creation of knowledge involving scientists and stakeholders, especially those historically excluded from the design and implementation of urban development policies. 

Strategies to create organized multicomponent nanostructures composed of discrete, self-sorted domains are important for developing materials that mimic the complexity and multifunctionality found in biological systems. These structures can be challenging to achieve due to the required balance of molecular self-recognition and supramolecular attraction needed between the components. Herein, we report a strategy to construct a two-component nanostructure via a hierarchical assembly process whereby two monomeric building blocks undergo self-sorting assembly at the molecular level followed by a supramolecular association to form a nanofiber-wrapped nanotube. The two molecules self-sorted into respective nanofiber and nanotube assemblies, yet assembly of the nanofibers in the presence of the nanotube template allowed for directed integration into a hierarchical multilayer structure via electrostatic interactions. The fiber-wrapped nanotube co-assembly was characterized using transmission electron microscopy (TEM), atomic force microscopy (AFM) and Förster resonance energy transfer (FRET) between the components. Strategies to co-assemble multicomponent nanostructures composed of discrete, spatially sorted domains with controllable higher level interactions will be critical for the development of novel, functionally competent nanomaterials. 

Abstract Missing heritability in genome-wide association studies defines a major problem in genetic analyses of complex biological traits 1,2 . The solution to this problem is to identify all causal genetic variants and to measure their individual contributions 3,4 . Here we report a graph pangenome of tomato constructed by precisely cataloguing more than 19 million variants from 838 genomes, including 32 new reference-level genome assemblies. This graph pangenome was used for genome-wide association study analyses and heritability estimation of 20,323 gene-expression and metabolite traits. The average estimated trait heritability is 0.41 compared with 0.33 when using the single linear reference genome. This 24% increase in estimated heritability is largely due to resolving incomplete linkage disequilibrium through the inclusion of additional causal structural variants identified using the graph pangenome. Moreover, by resolving allelic and locus heterogeneity, structural variants improve the power to identify genetic factors underlying agronomically important traits leading to, for example, the identification of two new genes potentially contributing to soluble solid content. The newly identified structural variants will facilitate genetic improvement of tomato through both marker-assisted selection and genomic selection. Our study advances the understanding of the heritability of complex traits and demonstrates the power of the graph pangenome in crop breeding. 

Diabetes poses a high risk for debilitating complications in neural tissues, regulating glucose uptake through insulin-dependent and predominantly insulin-independent pathways. Supramolecular nanostructures provide a flexible strategy for combinatorial regulation of glycemia. Here, we compare the effects of free insulin to insulin bound to positively charged nanofibers comprised of self-assembling amino acid compounds (AACs) with an antioxidant-modified side chain moiety (AAC2) in both in vitro and in vivo models of type 1 diabetes. Free AAC2, free human insulin (hINS) and AAC2-bound-human insulin (AAC2-hINS) were tested in streptozotocin (STZ)-induced mouse model of type 1 diabetes. AAC2-hINS acted as a complex and exhibited different properties compared to free AAC2 or hINS. Mice treated with the AAC2-hINS complex were devoid of hypoglycemic episodes, had improved levels of insulin in circulation and in the brain, and increased expression of neurotransmitter taurine transporter, Slc6a6. Consequently, treatment with AAC2-hINS markedly advanced both physical and cognitive performance in mice with STZ-induced and genetic type 1 diabetes compared to treatments with free AAC2 or hINS. This study demonstrates that the flexible nanofiber AAC2 can serve as a therapeutic platform for the combinatorial treatment of diabetes and its complications.