Micro-manufacturing : research, technology outcomes and development issues

Besides continuing effort in developing MEMS-based manufacturing techniques, latest effort in Micro-manufacturing is also in Non-MEMS-based manufacturing. Research and technological development (RTD) in this field is encouraged by the increased demand on micro-components as well as promised development in the scaling down of the traditional macro-manufacturing processes for micro-length-scale manufacturing. This paper highlights some EU funded research activities in micro/nano-manufacturing, and gives examples of the latest development in micro-manufacturing methods/techniques, process chains, hybrid-processes, manufacturing equipment and supporting technologies/device, etc., which is followed by a summary of the achievements of the EU MASMICRO project. Finally, concluding remarks are given, which raise several issues concerning further development in micro-manufacturing

The catalytic subunit of the system L1 amino acid transporter (S<i>lc7a5</i>) facilitates nutrient signalling in mouse skeletal muscle

The System L1-type amino acid transporter mediates transport of large neutral amino acids (LNAA) in many mammalian cell-types. LNAA such as leucine are required for full activation of the mTOR-S6K signalling pathway promoting protein synthesis and cell growth. The SLC7A5 (LAT1) catalytic subunit of high-affinity System L1 functions as a glycoprotein-associated heterodimer with the multifunctional protein SLC3A2 (CD98). We generated a floxed Slc7a5 mouse strain which, when crossed with mice expressing Cre driven by a global promoter, produced Slc7a5 heterozygous knockout (Slc7a5+/-) animals with no overt phenotype, although homozygous global knockout of Slc7a5 was embryonically lethal. Muscle-specific (MCK Cre-mediated) Slc7a5 knockout (MS-Slc7a5-KO) mice were used to study the role of intracellular LNAA delivery by the SLC7A5 transporter for mTOR-S6K pathway activation in skeletal muscle. Activation of muscle mTOR-S6K (Thr389 phosphorylation) in vivo by intraperitoneal leucine injection was blunted in homozygous MS-Slc7a5-KO mice relative to wild-type animals. Dietary intake and growth rate were similar for MS-Slc7a5-KO mice and wild-type littermates fed for 10 weeks (to age 120 days) with diets containing 10%, 20% or 30% of protein. In MS-Slc7a5-KO mice, Leu and Ile concentrations in gastrocnemius muscle were reduced by ∼40% as dietary protein content was reduced from 30 to 10%. These changes were associated with >50% decrease in S6K Thr389 phosphorylation in muscles from MS-Slc7a5-KO mice, indicating reduced mTOR-S6K pathway activation, despite no significant differences in lean tissue mass between groups on the same diet. MS-Slc7a5-KO mice on 30% protein diet exhibited mild insulin resistance (e.g. reduced glucose clearance, larger gonadal adipose depots) relative to control animals. Thus, SLC7A5 modulates LNAA-dependent muscle mTOR-S6K signalling in mice, although it appears non-essential (or is sufficiently compensated by e.g. SLC7A8 (LAT2)) for maintenance of normal muscle mass

Discovery of SQSTM1/p62-dependent P-bodies that regulate the NLRP3 inflammasome

Autophagy and ribonucleoprotein granules, such as P-bodies (PBs) and stress granules, represent vital stress responses to maintain cellular homeostasis. SQSTM1/p62 phase-separated droplets are known to play critical roles in selective autophagy; however, it is unknown whether p62 can exist as another form in addition to its autophagic droplets. Here, we found that, under stress conditions, including proteotoxicity, endotoxicity, and oxidation, autophagic p62 droplets are transformed to a type of enlarged PBs, termed p62-dependent P-bodies (pd-PBs). p62 phase separation is essential for the nucleation of pd-PBs. Mechanistically, pd-PBs are triggered by enhanced p62 droplet formation upon stress stimulation through the interactions between p62 and DDX6, a DEAD-box ATPase. Functionally, pd-PBs recruit the NLRP3 inflammasome adaptor ASC to assemble the NLRP3 inflammasome and induce inflammation-associated cytotoxicity. Our study shows that p62 droplet-to-PB transformation acts as a stress response to activate the NLRP3 inflammasome process, suggesting that persistent pd-PBs lead to NLRP3-dependent inflammation toxicity

Hypoxia and Prostaglandin E Receptor 4 Signalling Pathways Synergise to Promote Endometrial Adenocarcinoma Cell Proliferation and Tumour Growth

The prostaglandin endoperoxide synthase (PTGS) pathway is a potent driver of tumour development in humans by enhancing the biosynthesis and signalling of prostaglandin (PG) E2. PTGS2 expression and PGE2 biosynthesis is elevated in endometrial adenocarcinoma, however the mechanism whereby PTGS and PGE2 regulate endometrial tumour growth is unknown. Here we investigated (a) the expression profile of the PGE synthase enzymes (PTGES, PTGES-2, PTGES-3) and PGE receptors (PTGER1–4) in endometrial adenocarcinomas compared with normal endometrium and (b) the role of PTGER4 in endometrial tumorigenesis in vivo. We found elevated expression of PTGES2 and PTGER4 and suppression of PTGER1 and PTGER3 in endometrial adenocarcinomas compared with normal endometrium. Using WT Ishikawa endometrial adenocarcinoma cells and Ishikawa cells stably transfected with the full length PTGER4 cDNA (PTGER4 cells) xenografted in the dorsal flanks of nude mice, we show that PTGER4 rapidly and significantly enhances tumour growth rate. Coincident with enhanced PTGER4-mediated tumour growth we found elevated expression of PTGS2 in PTGER4 xenografts compared with WT xenografts. Furthermore we found that the augmented growth rate of the PTGER4 xenografts was not due to enhanced angiogenesis, but regulated by an increased proliferation index and hypoxia. In vitro, we found that PGE2 and hypoxia independently induce expression of PTGER4 indicating two independent pathways regulating prostanoid receptor expression. Finally we have shown that PGE2 and hypoxia synergise to promote cellular proliferation of endometrial adenocarcinoma cells

Measurement of the proton form factor by studying e+e−→ppˉe^{+} e^{-}\rightarrow p\bar{p}

Using data samples collected with the BESIII detector at the BEPCII collider, we measure the Born cross section of $e^{+}e^{-}\rightarrow p\bar{p}$ at 12 center-of-mass energies from 2232.4 to 3671.0 MeV. The corresponding effective electromagnetic form factor of the proton is deduced under the assumption that the electric and magnetic form factors are equal $(|G_{E}|= |G_{M}|)$. In addition, the ratio of electric to magnetic form factors, $|G_{E}/G_{M}|$, and $|G_{M}|$ are extracted by fitting the polar angle distribution of the proton for the data samples with larger statistics, namely at $\sqrt{s}=$ 2232.4 and 2400.0 MeV and a combined sample at $\sqrt{s}$ = 3050.0, 3060.0 and 3080.0 MeV, respectively. The measured cross sections are in agreement with recent results from BaBar, improving the overall uncertainty by about 30\%. The $|G_{E}/G_{M}|$ ratios are close to unity and consistent with BaBar results in the same $q^{2}$ region, which indicates the data are consistent with the assumption that $|G_{E}|=|G_{M}|$ within uncertainties.Comment: 13 pages, 24 figure

Observation of the isospin-violating decay J/ψ→ϕπ0f0(980)J/\psi \to \phi\pi^{0}f_{0}(980)

Using a sample of 1.31 billion $J/\psi$ events collected with the BESIII detector at the BEPCII collider, the decays $J/\psi \to \phi \pi^{+}\pi^{-}\pi^{0}$ and $J/\psi \to \phi \pi^{0}\pi^{0}\pi^{0}$ are investigated. The isospin violating decay $J/\psi \to \phi \pi^{0} f_{0}(980)$ with $f_{0}(980) \to \pi\pi$, is observed for the first time. The width of the $f_{0}(980)$ obtained from the dipion mass spectrum is found to be much smaller than the world average value. In the $\pi^{0} f_{0}(980)$ mass spectrum, there is evidence of $f_1(1285)$ production. By studying the decay $J/\psi \to \phi\eta'$, the branching fractions of $\eta' \to \pi^{+}\pi^{-}\pi^{0}$ and $\eta' \to \pi^{0}\pi^{0}\pi^{0}$, as well as their ratio, are also measured.Comment: 10 pages, 10 figures, published in Phys. Rev.

An amplitude analysis of the π0π0\pi^{0}\pi^{0} system produced in radiative J/ψJ/\psi decays

An amplitude analysis of the $\pi^{0}\pi^{0}$ system produced in radiative $J/\psi$ decays is presented. In particular, a piecewise function that describes the dynamics of the $\pi^{0}\pi^{0}$ system is determined as a function of $M_{\pi^{0}\pi^{0}}$ from an analysis of the $(1.311\pm0.011)\times10^{9}$ $J/\psi$ decays collected by the BESIII detector. The goal of this analysis is to provide a description of the scalar and tensor components of the $\pi^0\pi^0$ system while making minimal assumptions about the properties or number of poles in the amplitude. Such a model-independent description allows one to integrate these results with other related results from complementary reactions in the development of phenomenological models, which can then be used to directly fit experimental data to obtain parameters of interest. The branching fraction of $J/\psi \to \gamma \pi^{0}\pi^{0}$ is determined to be $(1.15\pm0.05)\times10^{-3}$, where the uncertainty is systematic only and the statistical uncertainty is negligible.Comment: Submitted to Phys. Rev. D 19 pages, 4 figure

Extension of Murray's law using a non-Newtonian model of blood flow

<p>Abstract</p> <p>Background</p> <p>So far, none of the existing methods on Murray's law deal with the non-Newtonian behavior of blood flow although the non-Newtonian approach for blood flow modelling looks more accurate.</p> <p>Modeling</p> <p>In the present paper, Murray's law which is applicable to an arterial bifurcation, is generalized to a non-Newtonian blood flow model (power-law model). When the vessel size reaches the capillary limitation, blood can be modeled using a non-Newtonian constitutive equation. It is assumed two different constraints in addition to the pumping power: the volume constraint or the surface constraint (related to the internal surface of the vessel). For a seek of generality, the relationships are given for an arbitrary number of daughter vessels. It is shown that for a cost function including the volume constraint, classical Murray's law remains valid (i.e. Σ<it>R</it>^{<it>c </it>}= <it>cste </it>with <it>c </it>= 3 is verified and is independent of <it>n</it>, the dimensionless index in the viscosity equation; <it>R </it>being the radius of the vessel). On the contrary, for a cost function including the surface constraint, different values of <it>c </it>may be calculated depending on the value of <it>n</it>.</p> <p>Results</p> <p>We find that <it>c </it>varies for blood from 2.42 to 3 depending on the constraint and the fluid properties. For the Newtonian model, the surface constraint leads to <it>c </it>= 2.5. The cost function (based on the surface constraint) can be related to entropy generation, by dividing it by the temperature.</p> <p>Conclusion</p> <p>It is demonstrated that the entropy generated in all the daughter vessels is greater than the entropy generated in the parent vessel. Furthermore, it is shown that the difference of entropy generation between the parent and daughter vessels is smaller for a non-Newtonian fluid than for a Newtonian fluid.</p

Vibration suppression and angle tracking of a fire-rescue ladder

This paper mainly considers vibration suppression and angle tracking of a fire-rescue ladder system. The dynamical model is regarded as a segmented Euler–Bernoulli beam with gravity and tip mass, described by a set of motion equations and boundary conditions. Based on the nonlinear Euler–Bernoulli beam model, two active boundary controllers are proposed to achieve the control objectives. The elastic deflection and the angular error in the closed-loop system are proven to converge exponentially to a small neighborhood of zero. Numerical simulations based on finite difference method verify the effectiveness and the ascendancy of active boundary controllers