On the amplitudes for the CP-conserving K±(KS)→π±(π0)ℓ+ℓ−K^\pm(K_S)\to\pi^\pm(\pi^0)\ell^+\ell^- rare decay modes

The amplitudes for the rare decay modes $K^\pm\to\pi^\pm\ell^+\ell^-$ and $K_S\to\pi^0\ell^+\ell^-$ are studied with the aim of obtaining predictions for them, such as to enable the possibility to search for violations of lepton-flavour universality in the kaon sector. The issue is first addressed from the perspective of the low-energy expansion, and a two-loop representation of the corresponding form factors is constructed, leaving as unknown quantities their values and slopes at vanishing momentum transfer. In a second step a phenomenological determination of the latter is proposed. It consists of the contribution of the resonant two-pion state in the $P$ wave, and of the leading short-distance contribution determined by the operator-product expansion. The interpolation between the two energy regimes is described by an infinite tower of zero-width resonances matching the QCD short-distance behaviour. Finally, perspectives for future improvements in the theoretical understanding of these amplitudes are discussed.Comment: 49 pages, 11 figures, matches the published versio

AN EXAMINATION OF HIGH SCHOOL STUDENTS\u27 EXPERIENCES AS ANTI-DEFAMATION LEAGUE PEER TRAINERS: A CASE STUDY

The purpose of this qualitative case study was to examine students experiences as Anti-Defamation League (ADL) Peer Trainers at a predominately White, suburban high school in New Jersey, including in what ways students\u27 experiences reflected transformative learning and empowered them as social justice allies. In addition, the study explored in what ways students\u27 experiences could inform social justice education at their high school. The findings indicate that within this context, many participants experienced at least the beginning of perspective transformation, resulting in a shift from an exclusive to an inclusive perspective and an orientation toward social justice. Further, the findings suggest that adolescence may be an asset when the goal is to teach for transformation, as some participants developed a positive self-image related to their roles, and many felt empowered by their experiences

Measurement of the muon anomaly to high and even higher precision

Our recent series of measurements at Brookhaven National Laboratory determined the muon anomalous magnetic moment \amu to a precision of 0.5 ppm. The final result--representing the average of five running periods using both positive and negative muons--is \amu ^\pm = 11 659 208(6) \times 10^{-10}. It lies 2.7 standard deviations above the standard model expectation, which is based on updates given at this Workshop. Importantly, only the $e^{+}e^{-}$ annihilation and new KLOE radiative return data are used for the hadronic vacuum polarization input. Because the systematic limit has not been reached in the experiment, a new effort has been proposed and approved with the highest scientific priority at Brookhaven. The goal is an experimental uncertainty of 0.2 ppm, a 2.5-fold reduction in the overall experimental uncertainty. To do so will require a suite of upgrades and several qualitative changes in the philosophy of how the measurement is carried out. I discuss the old and new experiments with a particular emphasis on the technical matters that require change for the future.Comment: 10 pages, Proceedings of the 8th International Workshop on Tau-Lepton Physic

Contribution of Filopodia to Cell Migration: A Mechanical Link between Protrusion and Contraction

Numerous F-actin containing structures are involved in regulating protrusion of membrane at the leading edge of motile cells. We have investigated the structure and dynamics of filopodia as they relate to events at the leading edge and the function of the trailing actin networks. We have found that although filopodia contain parallel bundles of actin, they contain a surprisingly nonuniform spatial and temporal distribution of actin binding proteins. Along the length of the actin filaments in a single filopodium, the most distal portion contains primarily T-plastin, while the proximal portion is primarily bound by α-actinin and coronin. Some filopodia are stationary, but lateral filopodia move with respect to the leading edge. They appear to form a mechanical link between the actin polymerization network at the front of the cell and the myosin motor activity in the cell body. The direction of lateral filopodial movement is associated with the direction of cell migration. When lateral filopodia initiate from and move toward only one side of a cell, the cell will turn opposite to the direction of filopodial flow. Therefore, this filopodia-myosin II system allows actin polymerization driven protrusion forces and myosin II mediated contractile force to be mechanically coordinated

Why do we need the new BNL muon g-2 experiment now?

New final results from the CMD-2 and SND e+e- annihilation experiments, together with radiative return measurements from BaBar, lead to recent improvements in the standard model prediction for the muon anomaly. The uncertainty at 0.48 ppm--a largely data-driven result--is now slightly below the experimental uncertainty of 0.54 ppm. The difference, a_mu(expt)- a_mu(SM) = (27.6 +/- 8.4) x 10^-10, represents a 3.3 standard deviation effect. At this level, it is one of the most compelling indicators of physics beyond the standard model and, at the very least, a major constraint for speculative new theories such as SUSY or extra dimensions. Others at this Workshop detailed further planned standard model theory improvements to a_mu. Here I outline how BNL E969 will achieve a factor of 2 or more reduction in the experimental uncertainty. The new experiment is based on a proven technique and track record. I argue that this work must be started now to have maximal impact on the interpretation of the new physics anticipated to be unearthed at the LHC.Comment: Invited Talk, Tau-06 Workshop, 10 pages, 5 figure

Metallothionein mediates leukocyte chemotaxis

BACKGROUND: Metallothionein (MT) is a cysteine-rich, metal-binding protein that can be induced by a variety of agents. Modulation of MT levels has also been shown to alter specific immune functions. We have noticed that the MT genes map close to the chemokines Ccl17 and Cx3cl1. Cysteine motifs that characterize these chemokines are also found in the MT sequence suggesting that MT might also act as a chemotactic factor. RESULTS: In the experiments reported here, we show that immune cells migrate chemotactically in the presence of a gradient of MT. This response can be specifically blocked by two different monoclonal anti-MT antibodies. Exposure of cells to MT also leads to a rapid increase in F-actin content. Incubation of Jurkat T cells with cholera toxin or pertussis toxin completely abrogates the chemotactic response to MT. Thus MT may act via G-protein coupled receptors and through the cyclic AMP signaling pathway to initiate chemotaxis. CONCLUSION: These results suggest that, under inflammatory conditions, metallothionein in the extracellular environment may support the beneficial movement of leukocytes to the site of inflammation. MT may therefore represent a "danger signal"; modifying the character of the immune response when cells sense cellular stress. Elevated metallothionein produced in the context of exposure to environmental toxicants, or as a result of chronic inflammatory disease, may alter the normal chemotactic responses that regulate leukocyte trafficking. Thus, MT synthesis may represent an important factor in immunomodulation that is associated with autoimmune disease and toxicant exposure

Hadronic Contributions to the Muon Anomaly in the Constituent Chiral Quark Model

The hadronic contributions to the anomalous magnetic moment of the muon which are relevant for the confrontation between theory and experiment at the present level of accuracy, are evaluated within the same framework: the constituent chiral quark model. This includes the contributions from the dominant hadronic vacuum polarization as well as from the next--to--leading order hadronic vacuum polarization, the contributions from the hadronic light-by-light scattering, and the contributions from the electroweak hadronic $Z\gamma\gamma$ vertex. They are all evaluated as a function of only one free parameter: the constituent quark mass. We also comment on the comparison between our results and other phenomenological evaluations.Comment: Several misprints corrected and a clarifying sentence added. Three figures superposed and two references added. Version to appear in JHE

Micro-Acoustic-Trap (µAT) for microparticle assembly in 3D

Acoustic tweezers facilitate the manipulation of objects using sound waves. With the current state of the technology one can only control mobility for a single or few microparticles. This article presents a state of the art system where an Acoustic Lens was used for developing a Micro-Acoustic Trap for microparticle assembly in 3D. The model particles, 2 µm diameter polystyrene beads in suspension, were driven via acoustic pressure to form a monolayer at wavelength-defined distances above the substrate defined by the focal point of an Acoustic Lens The transducer was driven at 89 MHz, mixed with 100 ms pulses at a repetition rate of 2 Hz. Beyond a threshold drive amplitude sufficient to overcome Brownian motion, this led to 2D assembly of the microparticles into close-packed rafts >80 µm across (∼5 wavelengths of the carrier wave and >40 particles across). This methodology was further extended to manipulation of live Dictyostelium discoideum amoebae. This approach therefore offers maneuverability in controlling or assembling micrometer-scale objects using continuous or pulsed focused acoustic radiation pressure

IMHOTEP A composite score integrating popular tools for predicting the functional consequences of non-synonymous sequence variants

The in silico prediction of the functional consequences of mutations is an important goal of human pathogenetics. However, bioinformatic tools that classify mutations according to their functionality employ different algorithms so that predictions may vary markedly between tools. We therefore integrated nine popular prediction tools (PolyPhen-2, SNPs&GO, MutPred, SIFT, MutationTaster2, Mutation Assessor and FATHMM as well as conservation-based Grantham Score and PhyloP) into a single predictor. The optimal combination of these tools was selected by means of a wide range of statistical modeling techniques, drawing upon 10 029 disease-causing single nucleotide variants (SNVs) from Human Gene Mutation Database and 10 002 putatively ‘benign’ non-synonymous SNVs from UCSC. Predictive performance was found to be markedly improved by model-based integration, whilst maximum predictive capability was obtained with either random forest, decision tree or logistic regression analysis. A combination of PolyPhen-2, SNPs&GO, MutPred, MutationTaster2 and FATHMM was found to perform as well as all tools combined. Comparison of our approach with other integrative approaches such as Condel, CoVEC, CAROL, CADD, MetaSVM and MetaLR using an independent validation dataset, revealed the superiority of our newly proposed integrative approach. An online implementation of this approach, IMHOTEP (‘Integrating Molecular Heuristics and Other Tools for Effect Prediction’), is provided at http://www.uni-kiel.de/medinfo/cgi-bin/predictor/

The Phagocytosis and Toxicity of Amorphous Silica

BACKGROUND: Inhalation of crystalline silica is known to cause an inflammatory reaction and chronic exposure leads to lung fibrosis and can progress into the disease, silicosis. Cultured macrophages bind crystalline silica particles, phagocytose them, and rapidly undergo apoptotic and necrotic death. The mechanism by which particles are bound and internalized and the reason particles are toxic is unclear. Amorphous silica has been considered to be a less toxic form, but this view is controversial. We compared the uptake and toxicity of amorphous silica to crystalline silica. METHODOLOGY/PRINCIPAL FINDINGS: Amorphous silica particles are phagocytosed by macrophage cells and a single internalized particle is capable of killing a cell. Fluorescent dextran is released from endo-lysosomes within two hours after silica treatment and Caspase-3 activation occurs within 4 hours. Interestingly, toxicity is specific to macrophage cell lines. Other cell types are resistant to silica particle toxicity even though they internalize the particles. The large and uniform size of the spherical, amorphous silica particles allowed us to monitor them during the uptake process. In mCherry-actin transfected macrophages, actin rings began to form 1-3 minutes after silica binding and the actin coat disassembled rapidly following particle internalization. Pre-loading cells with fluorescent dextran allowed us to visualize the fusion of phagosomes with endosomes during internalization. These markers provided two new ways to visualize and quantify particle internalization. At 37 °C the rate of amorphous silica internalization was very rapid regardless of particle coating. However, at room temperature, opsonized silica is internalized much faster than non-opsonized silica. CONCLUSIONS/SIGNIFICANCE: Our results indicate that amorphous and crystalline silica are both phagocytosed and both toxic to mouse alveolar macrophage (MH-S) cells. The pathway leading to apoptosis appears to be similar in both cases. However, the result suggests a mechanistic difference between FcγRIIA receptor-mediated and non-opsonized silica particle phagocytosis