Analysis of a Darcy-Cahn-Hilliard Diffuse Interface Model for the Hele-Shaw Flow and its Fully Discrete Finite Element Approximation

In this paper we present PDE and finite element analyses for a system of partial differential equations (PDEs) consisting of the Darcy equation and the Cahn-Hilliard equation, which arises as a diffuse interface model for the two phase Hele-Shaw flow. We propose a fully discrete implicit finite element method for approximating the PDE system, which consists of the implicit Euler method combined with a convex splitting energy strategy for the temporal discretization, the standard finite element discretization for the pressure and a split (or mixed) finite element discretization for the fourth order Cahn-Hilliard equation. It is shown that the proposed numerical method satisfies a mass conservation law in addition to a discrete energy law that mimics the basic energy law for the Darcy-Cahn-Hilliard phase field model and holds uniformly in the phase field parameter $\epsilon$. With help of the discrete energy law, we first prove that the fully discrete finite method is unconditionally energy stable and uniquely solvable at each time step. We then show that, using the compactness method, the finite element solution has an accumulation point that is a weak solution of the PDE system. As a result, the convergence result also provides a constructive proof of the existence of global-in-time weak solutions to the Darcy-Cahn-Hilliard phase field model in both two and three dimensions. Finally, we propose a nonlinear multigrid iterative algorithm to solve the finite element equations at each time step. Numerical experiments based on the overall solution method of combining the proposed finite element discretization and the nonlinear multigrid solver are presented to validate the theoretical results and to show the effectiveness of the proposed fully discrete finite element method for approximating the Darcy-Cahn-Hilliard phase field model.Comment: 30 pages, 4 tables, 2 figure

Extracellular Matrix Molecules Facilitating Vascular Biointegration

All vascular implants, including stents, heart valves and graft materials exhibit suboptimal biocompatibility that significantly reduces their clinical efficacy. A range of biomolecules in the subendothelial space have been shown to play critical roles in local regulation of thrombosis, endothelial growth and smooth muscle cell proliferation, making these attractive candidates for modulation of vascular device biointegration. However, classically used biomaterial coatings, such as fibronectin and laminin, modulate only one of these components; enhancing endothelial cell attachment, but also activating platelets and triggering thrombosis. This review examines a subset of extracellular matrix molecules that have demonstrated multi-faceted vascular compatibility and accordingly are promising candidates to improve the biointegration of vascular biomaterials

Targeted modulation of tropoelastin structure and assembly

Tropoelastin, as the monomer unit of elastin, assembles into elastic fibers that impart strength and resilience to elastic tissues. Tropoelastin is also widely used to manufacture versatile materials with specific mechanical and biological properties. The assembly of tropoelastin into elastic fibers or biomaterials is crucially influenced by key submolecular regions and specific residues within these domains. In this work, we identify the functional contributions of two rarely occurring negatively charged residues, glutamate 345 in domain 19 and glutamate 414 in domain 21, in jointly maintaining the native conformation of the tropoelastin hinge, bridge and foot regions. Alanine substitution of E345 and/or E414 variably alters the positioning and interactive accessibility of these regions, as illustrated by nanostructural studies and detected by antibody and cell probes. These structural changes are associated with a lower propensity for monomer coacervation, cross-linking into morphologically and functionally atypical hydrogels, and markedly impaired and abnormal elastic fiber formation. Our work indicates the crucial significance of both E345 and E414 residues in modulating specific local structure and higher-order assembly of human tropoelastin

Subtle balance of tropoelastin molecular shape and flexibility regulates dynamics and hierarchical assembly

The assembly of the tropoelastin monomer into elastin is vital for conferring elasticity on blood vessels, skin, and lungs. Tropoelastin has dual needs for flexibility and structure in self-assembly. We explore the structure-dynamics-function interplay, consider the duality of molecular order and disorder, and identify equally significant functional contributions by local and global structures. To study these organizational stratifications, we perturb a key hinge region by expressing an exon that is universally spliced out in human tropoelastins. We find a herniated nanostructure with a displaced C terminus and explain by molecular modeling that flexible helices are replaced with substantial β sheets. We see atypical higher-order cross-linking and inefficient assembly into discontinuous, thick elastic fibers. We explain this dysfunction by correlating local and global structural effects with changes in the molecule’s assembly dynamics. This work has general implications for our understanding of elastomeric proteins, which balance disordered regions with defined structural modules at multiple scales for functional assembly.United States. Office of Naval Research (Presidential Early Career Award for Scientists and Engineers)National Institutes of Health (U.S.) (U01 EB014976

Long-Term Modeling of Wind Energy in the United States

An improved representation of wind energy has been developed for the ObjECTS MiniCAM integrated assessment modeling framework. The first version of this wind model was used for the CCTP scenarios, where wind accounts for between 9% and 17% of U.S. electricity generation by 2095. Climate forcing stabilization policies tend to increase projected deployment. Accelerated technological development in wind electric generation can both increase output and reduce the costs of wind energy. In all scenarios, wind generation is constrained by its costs relative to alternate electricity sources, particularly as less favorable wind farm sites are utilized. These first scenarios were based on exogenous resource estimates that do not allow evaluation of resource availability assumptions. A more detailed representation of wind energy is under development that uses spatially explicit resource information and explicit wind turbine technology characteristics

The Value of End-Use Energy Efficiency in Mitigation of U.S. Carbon Emissions

This report documents a scenario analysis exploring the value of advanced technologies in the U.S. buildings, industrial, and transportation sectors in stabilizing atmospheric greenhouse gas concentrations. The analysis was conducted by staff members of Pacific Northwest National Laboratory (PNNL), working at the Joint Global Change Research Institute (JGCRI) in support of the strategic planning process of the U.S. Department of Energy (U.S. DOE) Office of Energy Efficiency and Renewable Energy (EERE). The conceptual framework for the analysis is an integration of detailed buildings, industrial, and transportation modules into MiniCAM, a global integrated assessment model. The analysis is based on three technology scenarios, which differ in their assumed rates of deployment of new or presently available energy-saving technologies in the end-use sectors. These technology scenarios are explored with no carbon policy, and under two CO2 stabilization policies, in which an economic price on carbon is applied such that emissions follow prescribed trajectories leading to long-term stabilization of CO2 at roughly 450 and 550 parts per million by volume (ppmv). The costs of meeting the emissions targets prescribed by these policies are examined, and compared between technology scenarios. Relative to the reference technology scenario, advanced technologies in all three sectors reduce costs by 50% and 85% for the 450 and 550 ppmv policies, respectively. The 450 ppmv policy is more stringent and imposes higher costs than the 550 ppmv policy; as a result, the magnitude of the economic value of energy efficiency is four times greater for the 450 ppmv policy than the 550 ppmv policy. While they substantially reduce the costs of meeting emissions requirements, advanced end-use technologies do not lead to greenhouse gas stabilization without a carbon policy. This is due mostly to the effects of increasing service demands over time, the high consumption of fossil fuels in the electricity sector, and the use of unconventional feedstocks in the liquid fuel refining sector. Of the three end-use sectors, advanced transportation technologies have the greatest potential to reduce costs of meeting carbon policy requirements. Services in the buildings and industrial sectors can often be supplied by technologies that consume low-emissions fuels such as biomass or, in policy cases, electricity. Passenger transportation, in contrast, is especially unresponsive to climate policies, as the fuel costs are small compared to the time value of transportation and vehicle capital and operating costs. Delaying the transition from reference to advanced technologies by 15 years increases the costs of meeting 450 ppmv stabilization emissions requirements by 21%, but the costs are still 39% lower than the costs assuming reference technology. The report provides a detailed description of the end-use technology scenarios and provides a thorough analysis of the results. Assumptions are documented in the Appendix

FDG-PET/MRI for nonoperative management of rectal cancer: A prospective pilot study

Nonoperative management (NOM) is increasingly utilized for rectal cancer patients with a clinical complete response (cCR) following total neoadjuvant therapy (TNT). The objective of this pilot study was to determine whether FDG-PET/MRI alters clinical response assessments among stage I-III rectal cancer patients undergoing TNT followed by NOM, relative to MRI alone. This prospective study included 14 subjects with new rectal cancer diagnoses. Imaging consisted of FDG-PET/MRI for initial staging, post-TNT restaging, and surveillance during NOM. Two independent readers assessed treatment response on MRI followed by FDG-PET/MRI. Inter-reader differences were resolved by consensus review. The reference standard for post-TNT restaging consisted of surgical pathology or clinical follow-up. 7/14 subjects completed post-TNT restaging FDG-PET/MRIs. 5/7 subjects had evidence of residual disease and underwent total mesorectal excision; 2/7 subjects had initial cCR with no evidence of disease after 12 months of NOM. FDG-PET/MRI assessments of cCR status at post-TNT restaging had an accuracy of 100%, compared with 71% for MRI alone, as FDG-PET detected residual tumor in 2 more subjects. Inter-reader agreement for cCR status on FDG-PET/MRI was moderate (kappa, 0.56). FDG-PET provided added value in 82% (9/11) of restaging/surveillance scans. Our preliminary data indicate that FDG-PET/MRI can detect more residual disease after TNT than MRI alone, with the FDG-PET component providing added value in most restaging/surveillance scans

Novel Calicivirus Identified in Rabbits, Michigan, USA

This virus is distinct from rabbit hemorrhagic disease virus

The role of IL-36 and 37 in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has garnered considerable attention due to its morbidity and mortality. Although the precise mechanisms underlying HCC tumorigenesis remain to be elucidated, evidence suggests that host immunity plays a pivotal role in its development. IL-36 and IL-37 are important immunoregulatory cytokines classified as pro-inflammatory and anti-inflammatory respectively. In the context of HCC, the downregulation of intrahepatic IL-36 is inversely correlated with cirrhosis, but positively correlated with 5-year survival rates, suggesting that IL-36 offers protection during HCC development. However, IL-36 may lose its hepatoprotective effects as the disease progresses to HCC in the context of dysregulated immunity in cirrhotic patients. Substantially increased circulating IL-36 in HCC patients is likely a systemic response to HCC stimulation, but is insufficient to suppress progression towards HCC. Intrahepatic IL-37 is suppressed in HCC patients, consistent with the inverse correlation between intrahepatic IL-37 and the level of AFP in HCC patients, suggesting IL-37 exerts hepatoprotection. There is no significant difference in IL-37 among differentiations of HCC or with respect to clinical BCLC stages or cirrhosis status in HCC patients. However, IL-37 protection is demonstrated in an IL-37 transfected HCC animal model, showing significantly reduced tumour size. IL-36/37 may inhibit HCC by enhancing M1 tumour-associated macrophages while not affecting M2 macrophages. The interplay between IL-36 (pro-inflammatory) and IL-37 (anti-inflammatory) is emerging as a crucial factor in host protection against the development of HCC. Further research is needed to investigate the complex mechanisms involved and the therapeutic potential of targeting these cytokines in HCC management