Simon James Bytheway, Investing Japan; Foreign Capital, Monetary Standards, and Economic Development, 1859-2011, Harvard University Asia Center, 2014, 286. ISBN: 978-0-674-41713-7

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Narrow, Fast, and "Cool" Mantle Plumes Caused by Strain-Weakening Rheology in Earth's Lower Mantle

The rheological properties of Earth's lower mantle are key for mantle dynamics and planetary evolution. The main rock-forming minerals in the lower mantle are bridgmanite (Br) and smaller amounts of ferropericlase (Fp). Previous work has suggested that the large differences in viscosity between these minerals greatly affect the bulk rock rheology. The resulting effective rheology becomes highly strain-dependent as weaker Fp minerals become elongated and eventually interconnected. This implies that strain localization may occur in Earth's lower mantle. So far, there have been no studies on global-scale mantle convection in the presence of such strain-weakening (SW) rheology. Here, we present 2D numerical models of thermo-chemical convection in spherical annulus geometry including a new strain-dependent rheology formulation for lower mantle materials, combining rheological weakening and healing terms. We find that SW rheology has several direct and indirect effects on mantle convection. The most notable direct effect is the changing dynamics of weakened plume channels as well as the formation of larger thermochemical piles at the base of the mantle. The weakened plume conduits act as lubrication channels in the mantle and exhibit a lower thermal anomaly. SW rheology also reduces the overall viscosity, notable in terms of increasing convective vigor and core-mantle boundary heat flux. Finally, we put our results into context with existing hypotheses on the style of mantle convection and mixing. Most importantly, we suggest that the new kind of plume dynamics may explain the discrepancy between expected and observed thermal anomalies of deep-seated mantle plumes on Earth

A Three-Dimensional Computational Model of Collagen Network Mechanics

Extracellular matrix (ECM) strongly influences cellular behaviors, including cell proliferation, adhesion, and particularly migration. In cancer, the rigidity of the stromal collagen environment is thought to control tumor aggressiveness, and collagen alignment has been linked to tumor cell invasion. While the mechanical properties of collagen at both the single fiber scale and the bulk gel scale are quite well studied, how the fiber network responds to local stress or deformation, both structurally and mechanically, is poorly understood. This intermediate scale knowledge is important to understanding cell- ECM interactions and is the focus of this study. We have developed a three-dimensional elastic collagen fiber network model (bead-and-spring model) and studied fiber network behaviors for various biophysical conditions: collagen density, crosslinker strength, crosslinker density, and fiber orientation (random vs. prealigned). We found the best-fit crosslinker parameter values using shear simulation tests in a small strain region. Using this calibrated collagen model, we simulated both shear and tensile tests in a large linear strain region for different network geometry conditions. The results suggest that network geometry is a key determinant of the mechanical properties of the fiber network. We further demonstrated how the fiber network structure and mechanics evolves with a local formation, mimicking the effect of pulling by a pseudopod during cell migration. Our computational fiber network model is a step toward a full biomechanical model of cellular behaviors in various ECM conditions

Altering adsorbed proteins or cellular gene expression in bone-metastatic cancer cells affects PTHrP and Gli2 without altering cell growth

AbstractThe contents of this data in brief are related to the article titled “Matrix Rigidity Regulates the Transition of Tumor Cells to a Bone-Destructive Phenotype through Integrin β3 and TGF-β Receptor Type II”. In this DIB we will present our supplemental data investigating Integrin expression, attachment of cells to various adhesion molecules, and changes in gene expression in multiple cancer cell lines. Since the interactions of Integrins with adsorbed matrix proteins are thought to affect the ability of cancer cells to interact with their underlying substrates, we examined the expression of Integrin β1, β3, and β5 in response to matrix rigidity. We found that only Iβ3 increased with increasing substrate modulus. While it was shown that fibronectin greatly affects the expression of tumor-produced factors associated with bone destruction (parathyroid hormone-related protein, PTHrP, and Gli2), poly-l-lysine, vitronectin and type I collagen were also analyzed as potential matrix proteins. Each of the proteins was independently adsorbed on both rigid and compliant polyurethane films which were subsequently used to culture cancer cells. Poly-l-lysine, vitronectin and type I collagen all had negligible effects on PTHrP or Gli2 expression, but fibronectin was shown to have a dose dependent effect. Finally, altering the expression of Iβ3 demonstrated that it is required for tumor cells to respond to the rigidity of the matrix, but does not affect other cell growth or viability. Together these data support the data presented in our manuscript to show that the rigidity of bone drives Integrinβ3/TGF-β crosstalk, leading to increased expression of Gli2 and PTHrP

Synthesis of a Novel Biodegradable Polyurethane with Phosphatidylcholines

A novel polyurethane was successfully synthesized by chain-extension of biodegradable poly (l-lactide) functionalized phosphatidylcholine (PC) with hexamethylene diisocyanate (HDI) as chain extender (PUR-PC). The molecular weights, glass transition temperature (Tg) increased significantly after the chain-extension. The hydrophilicity of PUR-PC was better than the one without PC, according to a water absorption test. Moreover, the number of adhesive platelets and anamorphic platelets on PUR-PC film were both less than those on PUR film. These preliminary results suggest that this novel polyurethane might be a better scaffold than traditional biodegradable polyurethanes for tissue engineering due to its better blood compatibility. Besides, this study also provides a new method to prepare PC-modified biodegradable polyurethanes

Matrix Rigidity Induces Osteolytic Gene Expression of Metastatic Breast Cancer Cells

Nearly 70% of breast cancer patients with advanced disease will develop bone metastases. Once established in bone, tumor cells produce factors that cause changes in normal bone remodeling, such as parathyroid hormone-related protein (PTHrP). While enhanced expression of PTHrP is known to stimulate osteoclasts to resorb bone, the environmental factors driving tumor cells to express PTHrP in the early stages of development of metastatic bone disease are unknown. In this study, we have shown that tumor cells known to metastasize to bone respond to 2D substrates with rigidities comparable to that of the bone microenvironment by increasing expression and production of PTHrP. The cellular response is regulated by Rho-dependent actomyosin contractility mediated by TGF-ß signaling. Inhibition of Rho-associated kinase (ROCK) using both pharmacological and genetic approaches decreased PTHrP expression. Furthermore, cells expressing a dominant negative form of the TGF-ß receptor did not respond to substrate rigidity, and inhibition of ROCK decreased PTHrP expression induced by exogenous TGF-ß. These observations suggest a role for the differential rigidity of the mineralized bone microenvironment in early stages of tumor-induced osteolysis, which is especially important in metastatic cancer since many cancers (such as those of the breast and lung) preferentially metastasize to bone

Recent Advances in Synthetic Bioelastomers

This article reviews the degradability of chemically synthesized bioelastomers, mainly designed for soft tissue repair. These bioelastomers involve biodegradable polyurethanes, polyphosphazenes, linear and crosslinked poly(ether/ester)s, poly(ε-caprolactone) copolymers, poly(1,3-trimethylene carbonate) and their copolymers, poly(polyol sebacate)s, poly(diol-citrates) and poly(ester amide)s. The in vitro and in vivo degradation mechanisms and impact factors influencing degradation behaviors are discussed. In addition, the molecular designs, synthesis methods, structure properties, mechanical properties, biocompatibility and potential applications of these bioelastomers were also presented

Thermoresponsive, stretchable, biodegradable and biocompatible poly(glycerol sebacate)-based polyurethane hydrogels

Thermoresponsive, stretchable, biodegradable and biocompatible polyester-based polyurethane (PEU) hydrogels, based on poly(glycerol sebacate) pre-polymer and poly(ethylene glycol)s of different molecular masses were synthesized by a facile solvent-based two-step method. The chemical and physical characteristics of the PEU hydrogels are tunable, enabling the design of various negatively thermosensitive, mechanically stable and biodegradable systems. The PEU hydrogels demonstrate reversible responses to a change in medium temperature from 5 °C to 37 °C, with the swelling ratio at equilibrium varying from 499% to 12%. The hydrogels have a tensile Young’s modulus, ultimate tensile strength and elongation at break in the range of 0.02–0.20 MPa, 0.05–0.47 MPa and 426–623%, respectively, and show high stretchability and full shape recovery after compression. These are similar to the mechanical properties of adipose tissues. In vitro degradation tests show mass losses of 8.7–16.3% and 10.7–20.7% without and with the presence of lipase enzyme for 31 days, respectively. In vitro cell tests show clear evidence that some of the PEU hydrogels are suitable for culturing adipose-derived stem cells and dermal fibroblasts and hence for future soft tissue regeneration. The functionalities of the PEU hydrogels were also evaluated for potential applications in drug delivery, thermal actuation and ultralow power generation. The results demonstrate the versatility of these PEU hydrogels for a variety of biomedical and engineering application

Composite porous scaffold of PEG/PLA support improved bone matrix deposition in vitro compared to PLA‐only scaffolds

Controllable pore size and architecture are essential properties for tissue-engineering scaffolds to support cell ingrowth colonization. To investigate the effect of PEG addition on porosity and bone-cell behavior, porous Polylactic acid (PLA)-Polyethylene glycol (PEG) scaffolds were developed with varied weight ratios of PLA-PEG (100/0, 90/10, 75/25) using solvent casting and porogen leaching. Sugar 200-300 µm in size was used as a porogen. To assess their suitability for bone tissue engineering, MLO-A5 murine osteoblast cells were cultured and cell metabolic activity, alkaline phosphatase (ALP) activity and bone-matrix production determined (alizarin red S staining for calcium, direct red 80 staining for collagen). It was found that metabolic activity was significantly higher over time on scaffolds containing PEG, ALP activity and mineralized matrix production were also significantly higher on scaffolds containing 25% PEG. Porous architecture and cell distribution and penetration into the scaffold were analyzed using SEM and confocal microscopy, revealing that inclusion of PEG increased pore interconnectivity and therefore cell ingrowth in comparison to pure PLA scaffolds. The results of this study confirmed that PLA-PEG porous scaffolds support mineralizing osteoblasts better than pure PLA scaffolds, indicating they have a high potential for use in bone tissue engineering applications. This article is protected by copyright. All rights reserved