Adipose-derived stem cells (ASCs) are abundantly present in the mammary microenvironment and can promote breast cancer malignancy by differentiating into myofibroblasts. However, it remains largely unclear which role tumor-derived extracellular vesicles (TEVs) play in this process. Here, we used microfabricated, type I collagen-based 3-D tissue culture platforms to investigate the effect of breast cancer cell-derived TEVs on ASCs myofibroblast differentiation and consequential changes in extracellular matrix remodeling and vascular sprouting. TEVs collected from MDA MB-231 human metastatic breast cancer cells (MDAs) promoted ASC myofibroblast differentiation in both 2-D and 3-D culture as indicated by increased alpha smooth muscle actin (α-SMA) and fibronectin (Fn) levels. Correspondingly, TEV-treated ASCs were more contractile, secreted more vascular endothelial growth factor (VEGF), and promoted angiogenic sprouting of human umbilical vein endothelial cells. These changes were dependent on transforming growth factor beta (TGF-β)-related signaling and tumor cell glutaminase activity as their inhibition decreased TEV-related myofibroblastic differentiation of ASCs and related functional consequences. In summary, our data suggest that TEVs are important signaling factors that contribute to ASC desmoplastic reprogramming in the tumor microenvironment, and suggest that tumor cell glutamine metabolism may be used as a therapeutic target to interfere with this process.

GDP‐bound prenylated Rabs, sequestered by GDI (GDP dissociation inhibitor) in the cytosol, are delivered to destined sub‐cellular compartment and subsequently activated by GEFs (guanine nucleotide exchange factors) catalysing GDP‐to‐GTP exchange. The dissociation of GDI from Rabs is believed to require a GDF (GDI displacement factor). Only two RabGDFs, human PRA‐1 and Legionella pneumophila SidM/DrrA, have been identified so far and the molecular mechanism of GDF is elusive. Here, we present the structure of a SidM/DrrA fragment possessing dual GEF and GDF activity in complex with Rab1. SidM/DrrA reconfigures the Switch regions of the GTPase domain of Rab1, as eukaryotic GEFs do toward cognate Rabs. Structure‐based mutational analyses show that the surface of SidM/DrrA, catalysing nucleotide exchange, is involved in GDI1 displacement from prenylated Rab1:GDP. In comparison with an eukaryotic GEF TRAPP I, this bacterial GEF/GDF exhibits high binding affinity for Rab1 with GDP retained at the active site, which appears as the key feature for the GDF activity of the protein.

We develop short-channel transistors using solutionprocessed single-walled carbon nanotubes (SWNTs) to evaluate the feasibility of those SWNTs for high-performance applications. Our results show that even though the intrinsic field-effect mobility is lower than the mobility of CVD nanotubes, the electrical contact between the nanotube and metal electrodes is not significantly affected. It is this contact resistance which often limits the performance of ultrascaled transistors. Moreover, we found that the contact resistance is lowered by the introduction of oxygen treatment. Therefore, high-performance solution-processed nanotube transistors with a 15 nm channel length were obtained by combining a top-gate structure and gate insulators made of a high-dielectric-constant ZrO 2 film. The combination of these elements yields a performance comparable to that obtained with CVD nanotube transistors, which indicates the potential for using solution-processed SWNTs for future aggressively scaled transistor technology.

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Carbon nanotube networks in thin-film type transistors were studied experimentally, comparing the use of pre-separated semiconducting enriched nanotubes (90% and 99% purity) to examine how topology affects the properties of the devices. Measurements are reported for two deposition methods used for network formation: random and spin-aligned deposition methods. The results show that the thin-film transistors fabricated via spin-aligned deposition demonstrate better electrical uniformity and performance than those produced by the random network deposition method. Our results imply that coverage and alignment are strongly correlated with the properties of the devices and should therefore be simultaneously optimized for improved electrical uniformity and performance.Networks of single-walled carbon nanotubes (SWNTs) represent a class of electronic materials that can serve as high-performance channel layers in thin-film field effect transistors (TFTs) and other devices. 1-5 The favorable properties of such films may provide a route to practical nanotube-based electronic systems by eliminating the need for precise control over the properties or positions of individual SWNTs. Although single-tube devices can potentially achieve the intrinsic mobility of a semiconducting SWNT, 6 single-tube assembly methods are extremely challenging to scale up and are not yet technologically practical for largearea applications. Therefore, thin films of SWNTs consisting of either random or well-aligned networks represent a promising path to scalable device manufacturing. 7,8 However, such films may have a lower mobility than single-tube devices because tube-tube crossings limit the current flow from source to drain when the channel length is greater than the nanotube length. 9,10 Increasing the network density can increase the current but can also lead to a shorted TFTs 11 resulting from a detrimental increase in the probability of having a percolation path dominated by metallic species.The problem of the co-existence of metallic and semiconducting SWNTs can be addressed by using pre-purified semiconducting enriched SWNTs produced, for example, by density gradient ultracentrifugation. 12 However, limitations are also imposed in this process because cost-effective, 100% pure semiconducting nanotubes are not available. Therefore, all commercially available enriched solutions contain some amount of metallic nanotubes, which may negatively impact semiconducting device properties. To date, there has been progressive research based on highly preenriched semiconducting nanotubes (i.e., over 95% semiconducting nanotubes). 13,14 Nevertheless, many interesting issues remain to be studied. Open questions include whether improved performance can be achieved with separated nanotubes of lower enrichment (<95%) and how does network topology affect the transport and uniformity properties. 15 Here, we present the results of experimental studies designed to address these questions by evaluating the transport and uniformity properties of transistors fabric...