Die filling process simulation using discrete element method (DEM)

Powder compaction and sintering are important techniques for the mass production of geometrically complex parts. Powder is poured from a reservoir into the feeding shoe, which then passes the cavity one or more times thereby delivering powder into it. The powder is then compressed to create a relatively brittle green body. Finally, the green body is ejected from the cavity and sintered in a furnace where thermal activation below the melting point produces a fully dense structure. Necks form and grow between adjacent grains thereby eliminating the porosity of the part. In general, a consistent and uniform die filling process is always desirable. Heterogeneity during die filling can propagate through the subsequent processes and finally lead to serious product defects, such as cracking, low strength, distortion and shrinkage [1]. Capillary cohesion is known to influence strongly the strength and flow properties of granular materials. At low levels of water content, the water forms a discontinuous phase composed of interparticle bridges that are unevenly distributed in the bulk (the pendular state) [2]. For powder filling process these capillary forces may have strong influence in the particle dynamics and subsequent packing. An approach using discrete element method (DEM) simulation is proposed to reproduce die filling process and investigate process characteristics that affect final sand cake shape and may lead to in-homogeneities in powder during the filling process. Also an experimental apparatus able to reproduce the die filling process was built to validate numerical model. A coarse grain model is also necessary to reduce the model size (reduce the number of particles)

Constraining the Hadronic Contributions to the Muon Anomalous Magnetic Moment

The mini-proceedings of the Workshop on "Constraining the hadronic contributions to the muon anomalous magnetic moment" which included the "13th meeting of the Radio MonteCarLow WG" and the "Satellite meeting R-Measurements at BES-III" held in Trento from April 10th to 12th, 2013, are presented. This collaboration meeting aims to bring together the experimental e+e- collider communities from BaBar, Belle, BESIII, CMD2, KLOE, and SND, with theorists working in the fields of meson transitions form factors, hadronic contributions to (g-2)_\mu and effective fine structure constant, and development of Monte Carlo generator and Radiative Corrections for precision e+e- and tau physics.Comment: 45 pages, 17 contributions. Editors: P. Masjuan and G. Venanzon

Safety, tumor trafficking and immunogenicity of chimeric antigen receptor (CAR)-T cells specific for TAG-72 in colorectal cancer.

BackgroundT cells engineered to express chimeric antigen receptors (CARs) have established efficacy in the treatment of B-cell malignancies, but their relevance in solid tumors remains undefined. Here we report results of the first human trials of CAR-T cells in the treatment of solid tumors performed in the 1990s.MethodsPatients with metastatic colorectal cancer (CRC) were treated in two phase 1 trials with first-generation retroviral transduced CAR-T cells targeting tumor-associated glycoprotein (TAG)-72 and including a CD3-zeta intracellular signaling domain (CART72 cells). In trial C-9701 and C-9702, CART72 cells were administered in escalating doses up to 1010 total cells; in trial C-9701 CART72 cells were administered by intravenous infusion. In trial C-9702, CART72 cells were administered via direct hepatic artery infusion in patients with colorectal liver metastases. In both trials, a brief course of interferon-alpha (IFN-α) was given with each CART72 infusion to upregulate expression of TAG-72.ResultsFourteen patients were enrolled in C-9701 and nine in C-9702. CART72 manufacturing success rate was 100% with an average transduction efficiency of 38%. Ten patients were treated in CC-9701 and 6 in CC-9702. Symptoms consistent with low-grade, cytokine release syndrome were observed in both trials without clear evidence of on target/off tumor toxicity. Detectable, but mostly short-term (≤14 weeks), persistence of CART72 cells was observed in blood; one patient had CART72 cells detectable at 48 weeks. Trafficking to tumor tissues was confirmed in a tumor biopsy from one of three patients. A subset of patients had 111Indium-labeled CART72 cells injected, and trafficking could be detected to liver, but T cells appeared largely excluded from large metastatic deposits. Tumor biomarkers carcinoembryonic antigen (CEA) and TAG-72 were measured in serum; there was a precipitous decline of TAG-72, but not CEA, in some patients due to induction of an interfering antibody to the TAG-72 binding domain of humanized CC49, reflecting an anti-CAR immune response. No radiologic tumor responses were observed.ConclusionThese findings demonstrate the relative safety of CART72 cells. The limited persistence supports the incorporation of co-stimulatory domains in the CAR design and the use of fully human CAR constructs to mitigate immunogenicity

New Speakers and Language Revitalisation: Arpitan and Community (Re)formation

Today, it is uncontroversial to claim that France’s regional (minority) languages (RLs) are in decline. However, revitalisation movements have nonetheless continued to surface, and this chapter considers one by-product of such efforts: the emergence of new speakers in RL contexts. The term ‘new speaker’ refers to individuals who acquire the target language not through traditional transmission contexts (e.g. home, family), but instead as adults through language revitalisation initiatives. The chapter focuses on revitalisation efforts in the context of Francoprovençal, a severely endangered and understudied RL spoken transnationally across French, Italian and Swiss borders. A critical examination of current studies supplemented with recently collected empirical data shows new speakers to be central agents in a movement championing proto-nation-statehood across national borders, reorienting the region’s traditional sociolinguistic field

Adult Circadian Behavior in Drosophila Requires Developmental Expression of cycle, But Not period

Circadian clocks have evolved as internal time keeping mechanisms that allow anticipation of daily environmental changes and organization of a daily program of physiological and behavioral rhythms. To better examine the mechanisms underlying circadian clocks in animals and to ask whether clock gene expression and function during development affected subsequent daily time keeping in the adult, we used the genetic tools available in Drosophila to conditionally manipulate the function of the CYCLE component of the positive regulator CLOCK/CYCLE (CLK/CYC) or its negative feedback inhibitor PERIOD (PER). Differential manipulation of clock function during development and in adulthood indicated that there is no developmental requirement for either a running clock mechanism or expression of per. However, conditional suppression of CLK/CYC activity either via per over-expression or cyc depletion during metamorphosis resulted in persistent arrhythmic behavior in the adult. Two distinct mechanisms were identified that may contribute to this developmental function of CLK/CYC and both involve the ventral lateral clock neurons (LNvs) that are crucial to circadian control of locomotor behavior: (1) selective depletion of cyc expression in the LNvs resulted in abnormal peptidergic small-LNv dorsal projections, and (2) PER expression rhythms in the adult LNvs appeared to be affected by developmental inhibition of CLK/CYC activity. Given the conservation of clock genes and circuits among animals, this study provides a rationale for investigating a possible similar developmental role of the homologous mammalian CLOCK/BMAL1 complex

Observation of a charged charmoniumlike structure in e+e−→(D∗Dˉ∗)±π∓e^+e^- \to (D^{*} \bar{D}^{*})^{\pm} \pi^\mp at s=4.26\sqrt{s}=4.26GeV

We study the process $e^+e^- \to (D^{*} \bar{D}^{*})^{\pm} \pi^\mp$ at a center-of-mass energy of 4.26GeV using a 827pb$^{-1}$ data sample obtained with the BESIII detector at the Beijing Electron Positron Collider. Based on a partial reconstruction technique, the Born cross section is measured to be $(137\pm9\pm15)$pb. We observe a structure near the $(D^{*} \bar{D}^{*})^{\pm}$ threshold in the $\pi^\mp$ recoil mass spectrum, which we denote as the $Z^{\pm}_c(4025)$. The measured mass and width of the structure are $(4026.3\pm2.6\pm3.7)$MeV/c$^2$ and $(24.8\pm5.6\pm7.7)$MeV, respectively. Its production ratio $\frac{\sigma(e^+e^-\to Z^{\pm}_c(4025)\pi^\mp \to (D^{*} \bar{D}^{*})^{\pm} \pi^\mp)}{\sigma(e^+e^-\to (D^{*} \bar{D}^{*})^{\pm} \pi^\mp)}$ is determined to be $0.65\pm0.09\pm0.06$. The first uncertainties are statistical and the second are systematic.Comment: 7 pages, 4 figures, 1 table; version accepted to be published in PR

Observation of J/ψ→ppˉa0(980)J/\psi \rightarrow p\bar{p}a_{0}(980) at BESIII

Using $2.25\times10^{8}$ $J/\psi$ events collected with the BESIII detector at the BEPCII storage rings, we observe for the first time the process $J/\psi\rightarrow p\bar{p}a_{0}(980)$, $a_{0}(980)\rightarrow \pi^{0}\eta$ with a significance of $6.5\sigma$ ($3.2\sigma$ including systematic uncertainties). The product branching fraction of $J/\psi\rightarrow p\bar{p}a_{0}(980)\rightarrow p\bar{p}\pi^{0}\eta$ is measured to be $(6.8\pm1.2\pm1.3)\times 10^{-5}$, where the first error is statistical and the second is systematic. This measurement provides information on the $a_{0}$ production near threshold coupling to $p\bar{p}$ and improves the understanding of the dynamics of $J/\psi$ decays to four body processes.Comment: 8 pages, 7 figure

Measurement of azimuthal asymmetries in inclusive charged dipion production in e+e−e^+e^- annihilations at s\sqrt{s} = 3.65 GeV

We present a measurement of the azimuthal asymmetries of two charged pions in the inclusive process $e^+e^-\rightarrow \pi\pi X$ based on a data set of 62 $\rm{pb}^{-1}$ at the center-of-mass energy $\sqrt{s}=3.65$ GeV collected with the BESIII detector. These asymmetries can be attributed to the Collins fragmentation function. We observe a nonzero asymmetry, which increases with increasing pion momentum. As our energy scale is close to that of the existing semi-inclusive deep inelastic scattering experimental data, the measured asymmetries are important inputs for the global analysis of extracting the quark transversity distribution inside the nucleon and are valuable to explore the energy evolution of the spin-dependent fragmentation function.Comment: 7 pages, 5 figure

Measurement of the e+e−→π+π−\mathrm e^+\mathrm e^-\rightarrow\mathrm\pi^+\mathrm\pi^- Cross Section between 600 and 900 MeV Using Initial State Radiation

We extract the $e^+e^-\rightarrow \pi^+\pi^-$ cross section in the energy range between 600 and 900 MeV, exploiting the method of initial state radiation. A data set with an integrated luminosity of 2.93 fb$^{-1}$ taken at a center-of-mass energy of 3.773 GeV with the BESIII detector at the BEPCII collider is used. The cross section is measured with a systematic uncertainty of 0.9%. We extract the pion form factor $|F_\pi|^2$ as well as the contribution of the measured cross section to the leading order hadronic vacuum polarization contribution to $(g-2)_\mu$. We find this value to be $a_\mu^{\pi\pi,\rm LO}(600-900\;\rm MeV) = (368.2 \pm 2.5_{\rm stat} \pm 3.3_{\rm sys})\cdot 10^{-10}$.Comment: 14 pages, 7 figures, accepted by PL