Correlated metallic state of vanadium dioxide

The metal-insulator transition and unconventional metallic transport in vanadium dioxide (VO$_2$) are investigated with a combination of spectroscopic ellipsometry and reflectance measurements. The data indicates that electronic correlations, not electron-phonon interactions, govern charge dynamics in the metallic state of VO$_2$. This study focuses on the frequency and temperature dependence of the conductivity in the regime of extremely short mean free path violating the Ioffe-Regel-Mott limit of metallic transport. The standard quasiparticle picture of charge conduction is found to be untenable in metallic VO$_2$.Comment: 5 pages, 3 figure

Engineering of In Vitro 3D Capillary Beds by Self-Directed Angiogenic Sprouting

In recent years, microfluidic systems have been used to study fundamental aspects of angiogenesis through the patterning of single-layered, linear or geometric vascular channels. In vivo, however, capillaries exist in complex, three-dimensional (3D) networks, and angiogenic sprouting occurs with a degree of unpredictability in all x,y,z planes. The ability to generate capillary beds in vitro that can support thick, biological tissues remains a key challenge to the regeneration of vital organs. Here, we report the engineering of 3D capillary beds in an in vitro microfluidic platform that is comprised of a biocompatible collagen I gel supported by a mechanical framework of alginate beads. The engineered vessels have patent lumens, form robust ~1.5 mm capillary networks across the devices, and support the perfusion of 1 µm fluorescent beads through them. In addition, the alginate beads offer a modular method to encapsulate and co-culture cells that either promote angiogenesis or require perfusion for cell viability in engineered tissue constructs. This laboratory-constructed vascular supply may be clinically significant for the engineering of capillary beds and higher order biological tissues in a scalable and modular manner.Singapore-MIT Alliance for Research and Technolog

Emergent mechanical control of vascular morphogenesis

Vascularization is driven by morphogen signals and mechanical cues that coordinately regulate cellular force generation, migration, and shape change to sculpt the developing vascular network. However, it remains unclear whether developing vasculature actively regulates its own mechanical properties to achieve effective vascularization. We engineered tissue constructs containing endothelial cells and fibroblasts to investigate the mechanics of vascularization. Tissue stiffness increases during vascular morphogenesis resulting from emergent interactions between endothelial cells, fibroblasts, and ECM and correlates with enhanced vascular function. Contractile cellular forces are key to emergent tissue stiffening and synergize with ECM mechanical properties to modulate the mechanics of vascularization. Emergent tissue stiffening and vascular function rely on mechanotransduction signaling within fibroblasts, mediated by YAP1. Mouse embryos lacking YAP1 in fibroblasts exhibit both reduced tissue stiffness and develop lethal vascular defects. Translating our findings through biology-inspired vascular tissue engineering approaches will have substantial implications in regenerative medicine

Small molecule sensitization to TRAIL is mediated via nuclear localization, phosphorylation and inhibition of chaperone activity of Hsp27

10.1038/cddis.2013.413Cell Death and Disease410

3D Anastomosed Microvascular Network Model with Living Capillary Networks and Endothelial Cell-Lined Microfluidic Channels

This protocol describes detailed practical procedures for generating 3D intact and perfusable microvascular network that connects to microfluidic channels without appreciable leakage. This advanced 3D microvascular network model incorporates different stages of vascular development including vasculogenesis, endothelial cell (EC) lining, sprouting angiogenesis, and anastomosis in sequential order. The capillary network is first induced via vasculogenesis in a middle tissue chamber and then EC linings along the microfluidic channel on either side serve as artery and vein. The anastomosis is then induced by sprouting angiogenesis to facilitate tight interconnection between the artery/vein and the capillary network. This versatile device design and its robust construction methodology establish a physiological microcirculation transport model of interconnected perfused vessels from artery to vascularized tissue to vein

A systems perspective on the death of a car company

Purpose – The aim of this paper is to understand how large and apparently successful organizations enter spirals of decline that are very difficult to reverse. The paper examines the case of Rover, once one of the largest car producers in the world, which collapsed in 2005. An analysis of strategic and operational choices made over a period of 40 years investigates the reasons for, and consequences of, a growing mismatch between the context faced by the company (industry dynamics, market conditions) and its operational capabilities, a mismatch that ultimately brought about the company's demise. Design/methodology/approach – The paper is based on interviews with 32 people, including senior managers (including four chief executives), government ministers and union officials who were key decision makers within, or close to, the company during the period 1968 and 2005. Secondary sources and documentary evidence (e.g. production and sales data) are used to build up a historical picture of the company and to depict its deteriorating financial and market position from 1968 onwards. Findings – The company was formed from a multitude of previously independent firms as part of a government‐sponsored agenda to build a UK National Champion in the car industry. The merged company failed due to several factors including poor product development processes, poor manufacturing performance, difficult labour relations, a very wide product portfolio and a lack of financial control. Although strenuous efforts were made to address those issues, including periods of whole or part ownership by British Aerospace, Honda and BMW, the company's position deteriorated until eventually production volumes were too low for viable operation. Practical implications – The case of Rover highlights the importance of what has been termed “the management unit” in complex systems. The management unit comprises processes and routines to deal with challenges such as managing product portfolios, connecting strategic and operational choices, and scanning and responding to the environment. In the case of Rover, a number of factors taken together generated excessive load on a management unit frequently operating under conditions of resource scarcity. We conclude that viewing corporate failure from a systems perspective, rather than in terms of shortcomings in specific subsystems, such as manufacturing or product development, yields insights often absent in the operations management literature. Originality/value – The paper is of value by showing corporate failure from a systems perspective, rather than in terms of shortcomings in specific subsystems, such as manufacturing or product development; and yields insights often absent in the operations management literature. The Rover case featured in the paper demonstrates the usefulness of systems ideas to understanding at least some types of failure, not as an alterative to capability‐based approaches, but in addition to them

Emergent mechanical control of vascular morphogenesis

Vascularization is driven by morphogen signals and mechanical cues that coordinately regulate cellular force generation, migration, and shape change to sculpt the developing vascular network. However, it remains unclear whether developing vasculature actively regulates its own mechanical properties to achieve effective vascularization. We engineered tissue constructs containing endothelial cells and fibroblasts to investigate the mechanics of vascularization. Tissue stiffness increases during vascular morphogenesis resulting from emergent interactions between endothelial cells, fibroblasts, and ECM and correlates with enhanced vascular function. Contractile cellular forces are key to emergent tissue stiffening and synergize with ECM mechanical properties to modulate the mechanics of vascularization. Emergent tissue stiffening and vascular function rely on mechanotransduction signaling within fibroblasts, mediated by YAP1. Mouse embryos lacking YAP1 in fibroblasts exhibit both reduced tissue stiffness and develop lethal vascular defects. Translating our findings through biology-inspired vascular tissue engineering approaches will have substantial implications in regenerative medicine

Engineered Models of Metastasis with Application to Study Cancer Biomechanics

Three-dimensional complex biomechanical interactions occur from the initial steps of tumor formation to the later phases of cancer metastasis. Conventional monolayer cultures cannot recapitulate the complex microenvironment and chemical and mechanical cues that tumor cells experience during their metastatic journey, nor the complexity of their interactions with other, noncancerous cells. As alternative approaches, various engineered models have been developed to recapitulate specific features of each step of metastasis with tunable microenvironments to test a variety of mechanistic hypotheses. Here the main recent advances in the technologies that provide deeper insight into the process of cancer dissemination are discussed, with an emphasis on three-dimensional and mechanical factors as well as interactions between multiple cell types