1-D modelling and 3-D simulation of confined bubble formation and formation and pressure fluctuations during flow boiling in a microchannel with a rectangular cross-section of high aspect ratio

Copyright @ 2009 ASMEA simple 1-D model with low requirements for computing time is required to investigate parametric influences on the potentially adverse effects of pressure fluctuations driven by confined vapour bubble growth in microchannel evaporative cooling systems operating at high heat fluxes. A model is developed in this paper for the particular conditions of a channel of rectangular cross-section with high aspect ratio with a constant inlet flow rate (zero upstream compressibility). (The model will later be extended to the conditions of finite upstream compressibility that lead to transient flow reversal). Some parametric trends predicted by the model are presented. The simplifying assumptions in the model are examined in the light of a 3-D simulation by a commercial CFD code, described in an accompanying paper by the same authors. The predictions of pressure changes are in reasonable agreement. It is suggested that the 1-D model will be a useful design tool.This work is supported by the UK Engineering and Physical Sciences Research Council (EPSRC) under grants EP/D500095/1 and EP/D500125/1

Numerical simulation and experimental observations of confined bubble growth during flow boiling in a microchannel with rectangular cross-section of high aspect ratio

Bubble nucleation and growth to confinement during flow boiling in microchannels lead to high heat transfer coefficients. They may also create pressure fluctuations that change the superheat driving evaporation and cause flow reversals that promote transient dry-out and uneven distribution of flow between parallel channels. The work described in this paper is part of a programme to develop models for these processes that will aid the design of evaporative cooling systems for devices operating at high heat fluxes. Video observations of water boiling in a single copper channel of rectangular cross-section, 0.38 × 1.6 mm and a heated length 40 mm, were performed. The top side of the channel was a glass window. Results are presented for a heat flux, averaged over the area of the three metal sides, of 210 and 173 W/m2K for incompressible and compressible inlet flow conditions. The inlet pressure was about 1.12 bar and the mass flux was 747.5 kg/m2s for both conditions examined. The results demonstrated the strong influence of compressibility on the mode of bubble detachment and growth and therefore on flow patterns, pressure fluctuations and heat transfer rates. The fluid mechanics of boiling in this size channel were also successfully investigated by 3-D numerical simulation for bubbles growing at a defined rate with a fixed inlet flow rate using the 3-D CFD code FLUENT 6 (no upstream compressibility). The study examined the fluid mechanics of bubble motion with heat transfer, but the mass transfer across the bubble-liquid interface was not simulated in the present work. A small vapour bubble was injected at the wall to ensure the bubble generation is under a quasi nucleation condition. Its growth was driven by an internal source of vapour, at a rate derived by analysis of the experimental measurements of growth. The simulation reproduced well the observed motion and shape of the bubble. The simulation was then extended to model bubbles generated and growing randomly in a 2-D channel

Advances in piezoelectric thin films for acoustic biosensors, acoustofluidics and lab-on-chip applications

Recently, piezoelectric thin films including zinc oxide (ZnO) and aluminium nitride (AlN) have found a broad range of lab-on-chip applications such as biosensing, particle/cell concentrating, sorting/patterning, pumping, mixing, nebulisation and jetting. Integrated acoustic wave sensing/microfluidic devices have been fabricated by depositing these piezoelectric films onto a number of substrates such as silicon, ceramics, diamond, quartz, glass, and more recently also polymer, metallic foils and bendable glass/silicon for making flexible devices. Such thin film acoustic wave devices have great potential for implementing integrated, disposable, or bendable/flexible lab-on-a-chip devices into various sensing and actuating applications. This paper discusses the recent development in engineering high performance piezoelectric thin films, and highlights the critical issues such as film deposition, MEMS processing techniques, control of deposition/processing parametres, film texture, doping, dispersion effects, film stress, multilayer design, electrode materials/ designs and substrate selections. Finally, advances in using thin film devices for lab-on-chip applications are summarised and future development trends are identified.The authors acknowledge support from the Innovative electronic Manufacturing Research Centre (IeMRC) through the EPSRC funded flagship project SMART MICROSYSTEMS (FS/01/02/10), Knowledge Transfer Partnership No KTP010548, EPSRC project EP/L026899/1, EP/F063865/1; EP/F06294X/1, EP/P018998/1, the Royal Society-Research Grant (RG090609) and Newton Mobility Grant (IE161019) through Royal Society and NFSC, the Scottish Sensing Systems Centre (S3C), Royal Society of Edinburgh, Carnegie Trust Funding, Royal Academy of Engineering-Research Exchange with China and India, UK Fluidic Network and Special Interest Group-Acoustofluidics, the EPSRC Engineering Instrument Pool. We also acknowledge the National Natural Science Foundation of China (Nos. 61274037, 51302173), the Zhejiang Province Natural Science Fund (No. Z11101168), the Fundamental Research Funds for the Central Universities (No. 2014QNA5002), EP/D03826X/1, EP/ C536630/1, GR/T24524/01, GR/S30573/01, GR/R36718/01, GR/L82090/01, BBSRC/E11140. ZXT acknowledges the supports from the National Natural Science Foundation of China (61178018) and the NSAF Joint Foundation of China (U1630126 and U1230124) and Ph.D. Funding Support Program of Education Ministry of China (20110185110007) and the NSAF Joint Foundation of China (Grant No. U1330103) and the National Natural Science Foundation of China (No. 11304209). NTN acknowledges support from Australian Research Council project LP150100153. This work was partially supported by the European Commission through the 6th FP MOBILIS and 7th FP RaptaDiag project HEALTH-304814 and by the COST Action IC1208 and by the Ministerio de Economía y Competitividad del Gobierno de España through projects MAT2010-18933 and MAT2013-45957R

Inhibition of Intestinal Adenoma Formation in APCMin/+ Mice by Riccardin D, a Natural Product Derived from Liverwort Plant Dumortiera hirsuta

BACKGROUND: Mutation of tumor suppressor gene, adenomatous polyposis coli (APC), is the primary molecular event in the development of most intestinal carcinomas. Animal model with APC gene mutation is an effective tool for study of preventive approaches against intestinal carcinomas. We aimed to evaluate the effect of Riccardin D, a macrocyclic bisbibenzyl compound, as a chemopreventive agent against intestinal adenoma formation in APC(Min/+) mice. METHODS: APC(Min/+) mice were given Riccardin D by p.o. gavage for 7 weeks. Mice were sacrificed, and the number, size and histopathology of intestinal polyps were examined under a microscope. We performed immunohistochemical staining, western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) in intestinal polyps to investigate the mechanism of chemopreventive effect of Riccardin D. RESULTS: Riccardin D treatment resulted in a significant inhibition of intestinal adenoma formation, showing a reduction of polyp number by 41.7%, 31.1% and 44.4%, respectively, in proximal, middle and distal portions of small intestine. The activity of Riccardin D against polyp formation was more profound in colon, wherein Riccardin D decreased polyp number by 79.3%. Size distribution analysis revealed a significant reduction in large-size polyps (2-3 mm) by 40.0%, 42.5% and 33.3%, respectively, in proximal, middle and distal portions of small intestine, and 77.8% in colon. Histopathological analysis of the intestinal polyps revealed mostly hyperplastic morphology without obvious dysplasia in Riccardin D-treated mice. Molecular analyses of the polyps suggested that the inhibitory effect of Riccardin D on intestinal adenoma formation was associated with its abilities of reduction in cell proliferation, induction of apoptosis, antiangiogenesis, inhibition of the Wnt signaling pathway and suppression of inflammatory mediators in polyps. CONCLUSIONS: Our results suggested that Riccardin D exerts its chemopreventive effect against intestinal adenoma formation through multiple mechanisms including anti-proliferative, apoptotic, anti-angiogenic and anti-inflammatory activity

Understanding the Warburg effect and the prognostic value of stromal caveolin-1 as a marker of a lethal tumor microenvironment

Cancer cells show a broad spectrum of bioenergetic states, with some cells using aerobic glycolysis while others rely on oxidative phosphorylation as their main source of energy. In addition, there is mounting evidence that metabolic coupling occurs in aggressive tumors, between epithelial cancer cells and the stromal compartment, and between well-oxygenated and hypoxic compartments. We recently showed that oxidative stress in the tumor stroma, due to aerobic glycolysis and mitochondrial dysfunction, is important for cancer cell mutagenesis and tumor progression. More specifically , increased autophagy/mitophagy in the tumor stroma drives a form of parasitic epithelial-stromal metabolic coupling. These findings explain why it is effective to treat tumors with either inducers or inhibitors of autophagy, as both would disrupt this energetic coupling. We also discuss evidence that glutamine addiction in cancer cells produces ammonia via oxidative mitochondrial metabolism. Ammonia production in cancer cells, in turn, could then help maintain autophagy in the tumor stromal compartment. In this vicious cycle, the initial glutamine provided to cancer cells would be produced by autophagy in the tumor stroma. Thus, we believe that parasitic epithelial-stromal metabolic coupling has important implications for cancer diagnosis and therapy, for example, in designing novel metabolic imaging techniques and establishing new targeted therapies. In direct support of this notion, we identified a loss of stromal caveolin-1 as a marker of oxidative stress, hypoxia, and autophagy in the tumor microenvironment, explaining its powerful predictive value. Loss of stromal caveolin-1 in breast cancers is associated with early tumor recurrence, metastasis, and drug resistance, leading to poor clinical outcome

Advances in modelling of biomimetic fluid flow at different scales

The biomimetic flow at different scales has been discussed at length. The need of looking into the biological surfaces and morphologies and both geometrical and physical similarities to imitate the technological products and processes has been emphasized. The complex fluid flow and heat transfer problems, the fluid-interface and the physics involved at multiscale and macro-, meso-, micro- and nano-scales have been discussed. The flow and heat transfer simulation is done by various CFD solvers including Navier-Stokes and energy equations, lattice Boltzmann method and molecular dynamics method. Combined continuum-molecular dynamics method is also reviewed

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe