Single molecule light field microscopy

We introduce single molecule light field microscopy (SMLFM), a new class of three-dimensional (3D) single molecule localization microscopy. By segmenting the back focal plane of a microscope objective with an array of microlenses to generate multiple 2D perspective views, the same single fluorophore can be imaged from different angles. These views, in combination with a bespoke fitting algorithm, enable the 3D positions of single fluorophores to be determined from parallax. SMLFM achieves up to 20 nm localization precision throughout an extended 6 µ m depth of field. The capabilities of SMLFM are showcased by imaging membranes of fixed eukaryotic cells and DNA nanostructures below the optical diffraction limit.</jats:p

Multiphoton Multispectral Fluorescence Lifetime Tomography for the Evaluation of Basal Cell Carcinomas

We present the first detailed study using multispectral multiphoton fluorescence lifetime imaging to differentiate basal cell carcinoma cells (BCCs) from normal keratinocytes. Images were acquired from 19 freshly excised BCCs and 27 samples of normal skin (in & ex vivo). Features from fluorescence lifetime images were used to discriminate BCCs with a sensitivity/specificity of 79%/93% respectively. A mosaic of BCC fluorescence lifetime images covering >1 mm2 is also presented, demonstrating the potential for tumour margin delineation. Using 10,462 manually segmented cells from the image data, we quantify the cellular morphology and spectroscopic differences between BCCs and normal skin for the first time. Statistically significant increases were found in the fluorescence lifetimes of cells from BCCs in all spectral channels, ranging from 19.9% (425–515 nm spectral emission) to 39.8% (620–655 nm emission). A discriminant analysis based diagnostic algorithm allowed the fraction of cells classified as malignant to be calculated for each patient. This yielded a receiver operator characteristic area under the curve for the detection of BCC of 0.83. We have used both morphological and spectroscopic parameters to discriminate BCC from normal skin, and provide a comprehensive base for how this technique could be used for BCC assessment in clinical practice

Fermion Condensates and the Trivial Vacuum of Light-Cone Quantum Field Theory

We discuss the definition of condensates within light-cone quantum field theory. As the vacuum state in this formulation is trivial, we suggest to abstract vacuum properties from the particle spectrum. The latter can in principle be calculated by solving the eigenvalue problem of the light-cone Hamiltonian. We focus on fermionic condensates which are order parameters of chiral symmetry breaking. As a paradigm identity we use the Gell-Mann-Oakes-Renner relation between the quark condensate and the observable pion mass. We examine the analogues of this relation in the `t~Hooft and Schwinger model, respectively. A brief discussion of the Nambu-Jona-Lasinio model is added.Comment: 14 pages, no figures, latex2

Variational Mass Perturbation Theory for Light-Front Bound-State Equations

We investigate the mesonic light-front bound-state equations of the 't Hooft and Schwinger model in the two-particle, i.e. valence sector, for small fermion mass. We perform a high precision determination of the mass and light-cone wave function of the lowest lying meson by combining fermion mass perturbation theory with a variational approach. All calculations are done entirely in the fermionic representation without using any bosonization scheme. In a step-by-step procedure we enlarge the space of variational parameters. For the first two steps, the results are obtained analytically. Beyond that we use computer algebraic and numerical methods. We achieve good convergence so that the calculation of the meson mass squared can be extended to third order in the fermion mass. Within the numerical treatment we include higher Fock states up to six particles. Our results are consistent with all previous numerical investigations, in particular lattice calculations. For the massive Schwinger model, we find a small discrepancy (less than 2 percent) in comparison with known bosonization results. Possible resolutions of this discrepancy are discussed.Comment: some points clarified, representation straightened, to appear in Phys. Rev. D, 31 pages, Latex, REVTeX, epsfig, 3 postscript figures include

Nonperturbative Light-Front QCD

In this work the determination of low-energy bound states in Quantum Chromodynamics is recast so that it is linked to a weak-coupling problem. This allows one to approach the solution with the same techniques which solve Quantum Electrodynamics: namely, a combination of weak-coupling diagrams and many-body quantum mechanics. The key to eliminating necessarily nonperturbative effects is the use of a bare Hamiltonian in which quarks and gluons have nonzero constituent masses rather than the zero masses of the current picture. The use of constituent masses cuts off the growth of the running coupling constant and makes it possible that the running coupling never leaves the perturbative domain. For stabilization purposes an artificial potential is added to the Hamiltonian, but with a coefficient that vanishes at the physical value of the coupling constant. The weak-coupling approach potentially reconciles the simplicity of the Constituent Quark Model with the complexities of Quantum Chromodynamics. The penalty for achieving this perturbative picture is the necessity of formulating the dynamics of QCD in light-front coordinates and of dealing with the complexities of renormalization which such a formulation entails. We describe the renormalization process first using a qualitative phase space cell analysis, and we then set up a precise similarity renormalization scheme with cutoffs on constituent momenta and exhibit calculations to second order. We outline further computations that remain to be carried out. There is an initial nonperturbative but nonrelativistic calculation of the hadronic masses that determines the artificial potential, with binding energies required to be fourth order in the coupling as in QED. Next there is a calculation of the leading radiative corrections to these masses, which requires our renormalization program. Then the real struggle of finding the right extensions to perturbation theory to study the strong-coupling behavior of bound states can begin.Comment: 56 pages (REVTEX), Report OSU-NT-94-28. (figures not included, available via anaonymous ftp from pacific.mps.ohio-state.edu in subdirectory pub/infolight/qcd

TGF-β1 Exerts Opposing Effects on Grass Carp Leukocytes: Implication in Teleost Immunity, Receptor Signaling and Potential Self-Regulatory Mechanisms

In fish immunity, the regulatory role of transforming growth factor-β1 (TGF-β1) has not been fully characterized. Here we examined the immunoregulatory effects of TGF-β1 in grass carp peripheral blood leukocytes (PBL) and head kidney leukocytes (HKL). It is interesting that TGF-β1 consistently stimulated the cell viability and the mRNA levels of pro-inflammatory cytokines (Tnfα and Ifnγ) and T/B cell markers [Cd4-like (Cd4l), Cd8α, Cd8β and Igμ] in PBL, which contrasted with its inhibitory tone in HKL. Further studies showed that grass carp TGF-β1 type I receptor, activin receptor-like kinase 5 (ALK5), was indispensable for the immunoregulatory effects of TGF-β1 in PBL and HKL. Notably, TGF-β1 persistently attenuated ALK5 expression, whereas immunoneutralization of endogenous grass carp TGF-β1 could increase ALK5 mRNA and protein levels. It is consistent with the observation that TGF-β1 decreased the number of ALK5+ leukocytes in PBL and HKL, revealing a negative regulation of TGF-β1 signaling at the receptor level. Moreover, transient treatment with TGF-β1 for 24 h was sufficient to induce similar cellular responses compared with the continuous treatment. This indicated a possible mechanism by which TGF-β1 triggered the down-regulation of ALK5 mRNA and protein, leading to the desensitization of grass carp leukocytes toward TGF-β1. Accordingly, our data revealed a dual role of TGF-β1 in teleost immunity in which it can serve as a positive or negative control device and provided additional mechanistic insights as to how TGF-β1 controls its signaling in vertebrate leukocytes

Search for the decay J/ψ→γ+invisibleJ/\psi\to\gamma + \rm {invisible}

We search for $J/\psi$ radiative decays into a weakly interacting neutral particle, namely an invisible particle, using the $J/\psi$ produced through the process $\psi(3686)\to\pi^+\pi^-J/\psi$ in a data sample of $(448.1\pm2.9)\times 10^6$ $\psi(3686)$ decays collected by the BESIII detector at BEPCII. No significant signal is observed. Using a modified frequentist method, upper limits on the branching fractions are set under different assumptions of invisible particle masses up to 1.2 $\mathrm{\ Ge\kern -0.1em V}/c^2$. The upper limit corresponding to an invisible particle with zero mass is 7.0$\times 10^{-7}$ at the 90\% confidence level

Sustained proliferation in cancer: mechanisms and novel therapeutic targets

Proliferation is an important part of cancer development and progression. This is manifest by altered expression and/or activity of cell cycle related proteins. Constitutive activation of many signal transduction pathways also stimulates cell growth. Early steps in tumor development are associated with a fibrogenic response and the development of a hypoxic environment which favors the survival and proliferation of cancer stem cells. Part of the survival strategy of cancer stem cells may manifested by alterations in cell metabolism. Once tumors appear, growth and metastasis may be supported by overproduction of appropriate hormones (in hormonally dependent cancers), by promoting angiogenesis, by undergoing epithelial to mesenchymal transition, by triggering autophagy, and by taking cues from surrounding stromal cells. A number of natural compounds (e.g., curcumin, resveratrol, indole-3-carbinol, brassinin, sulforaphane, epigallocatechin-3-gallate, genistein, ellagitannins, lycopene and quercetin) have been found to inhibit one or more pathways that contribute to proliferation (e.g., hypoxia inducible factor 1, nuclear factor kappa B, phosphoinositide 3 kinase/Akt, insulin-like growth factor receptor 1, Wnt, cell cycle associated proteins, as well as androgen and estrogen receptor signaling). These data, in combination with bioinformatics analyses, will be very important for identifying signaling pathways and molecular targets that may provide early diagnostic markers and/or critical targets for the development of new drugs or drug combinations that block tumor formation and progression

Measurement of proton electromagnetic form factors in e+e−→ppˉe^+e^- \to p\bar{p} in the energy region 2.00-3.08 GeV

The process of $e^+e^- \rightarrow p\bar{p}$ is studied at 22 center-of-mass energy points ($\sqrt{s}$) from 2.00 to 3.08 GeV, exploiting 688.5~pb$^{-1}$ of data collected with the BESIII detector operating at the BEPCII collider. The Born cross section~($\sigma_{p\bar{p}}$) of $e^+e^- \rightarrow p\bar{p}$ is measured with the energy-scan technique and it is found to be consistent with previously published data, but with much improved accuracy. In addition, the electromagnetic form-factor ratio ($|G_{E}/G_{M}|$) and the value of the effective ($|G_{\rm{eff}}|$), electric ($|G_E|$) and magnetic ($|G_M|$) form factors are measured by studying the helicity angle of the proton at 16 center-of-mass energy points. $|G_{E}/G_{M}|$ and $|G_M|$ are determined with high accuracy, providing uncertainties comparable to data in the space-like region, and $|G_E|$ is measured for the first time. We reach unprecedented accuracy, and precision results in the time-like region provide information to improve our understanding of the proton inner structure and to test theoretical models which depend on non-perturbative Quantum Chromodynamics

First observations of hc→h_c \to hadrons

Based on $(4.48 \pm 0.03) \times 10^{8}$ $\psi(3686)$ events collected with the BESIII detector, five $h_c$ hadronic decays are searched for via process $\psi(3686) \to \pi^0 h_c$. Three of them, $h_c \to p \bar{p} \pi^+ \pi^-$, $\pi^+ \pi^- \pi^0$, and $2(\pi^+ \pi^-) \pi^0$ are observed for the first time, with statistical significances of 7.4$\sigma$, $4.9\sigma$, and 9.1$\sigma$, and branching fractions of $(2.89\pm0.32\pm0.55)\times10^{-3}$, $(1.60\pm0.40\pm0.32)\times10^{-3}$, and $(7.44\pm0.94\pm1.56)\times10^{-3}$, respectively, where the first uncertainties are statistical and the second systematic. No significant signal is observed for the other two decay modes, and the corresponding upper limits of the branching fractions are determined to be $B(h_c \to 3(\pi^+ \pi^-) \pi^0)<8.7\times10^{-3}$ and $B(h_c \to K^+ K^- \pi^+ \pi^-)<5.8\times10^{-4}$ at 90% confidence level.Comment: 17 pages, 16 figure