SL(2,R) Yang-Mills theory on a circle

The kinematics of SL(2,R) Yang-Mills theory on a circle is considered, for reasons that are spelled out. The gauge transformations exhibit hyperbolic fixed points, and this results in a physical configuration space with a non-Hausdorff "network" topology. The ambiguity encountered in canonical quantization is then much more pronounced than in the compact case, and can not be resolved through the kind of appeal made to group theory in that case.Comment: 10 pages, Goteborg ITP 94-19, Contains two files: A latex file with all figures drawn in latex and a tar archive including a slightly modified latex file (uses psfig) and nicer postscript figures+necessary macro

The uses and functions of ageing celebrity war reporters

This article starts from the premise that recognition of professional authority and celebrity status depends on the embodiment and performance of field-specific dispositional practices: there’s no such thing as a natural, though we often talk about journalistic instinct as something someone simply has or doesn’t have. Next, we have little control over how we are perceived by peers and publics, and what we think are active positioning or subjectifying practices are in fact, after Bourdieu, revelations of already-determined delegation. The upshot is that two journalists can arrive at diametrically opposed judgements on the basis of observation of the same actions of a colleague, and as individuals we are blithely hypocritical in forming (or reciting) evaluations of the professional identity of celebrities. Nowhere is this starker than in the discourse of age-appropriate behaviour, which this paper addresses using the examples of ‘star’ war reporters John Simpson, Kate Adie and Martin Bell. A certain rough-around-the-edges irreverence is central to dispositional authenticity amongst war correspondents, and for ageing hacks this incorporates gendered attitudes to sex and alcohol as well as indifference to protocol. And yet perceived age-inappropriate sexual behaviour is also used to undermine professional integrity, and the paper ends by outlining the phenomenological context that makes possible this effortless switching between amoral and moralising recognition by peers and audiences alike

Measurement of the Electric and Magnetic Polarizabilities of the Proton

The Compton scattering cross section on the proton has been measured at laboratory angles of 90$^\circ$ and 135$^\circ$ using tagged photons in the energy range 70--100 MeV and simultaneously using untagged photons in the range 100--148~MeV. With the aid of dispersion relations, these cross sections were used to extract the electric and magnetic polarizabilities, $\bar{\alpha}$ and $\bar{\beta}$ respectively, of the proton. We find $$\bar{\alpha}+\bar{\beta} = ( 15.0 \pm 2.9 \pm 1.1 \pm 0.4 ) \times 10^{-4} \: {\rm fm}^3,$$ in agreement with a model-independent dispersion sum rule, and $$\bar{\alpha}-\bar{\beta} = ( 10.8 \pm 1.1 \pm 1.4 \pm 1.0 ) \times 10^{-4} \: {\rm fm}^3,$$ where the errors shown are statistical, systematic, and model-dependent, respectively. A comparison with previous experiments is given and global values for the polarizabilities are extracted.Comment: 35 pages, 11 PostScript figures, uses RevTex 3.

Targeting the CXCR4 pathway using a novel anti-CXCR4 IgG1 antibody (PF-06747143) in chronic lymphocytic leukemia.

BackgroundThe CXCR4-CXCL12 axis plays an important role in the chronic lymphocytic leukemia (CLL)-microenvironment interaction. Overexpression of CXCR4 has been reported in different hematological malignancies including CLL. Binding of the pro-survival chemokine CXCL12 with its cognate receptor CXCR4 induces cell migration. CXCL12/CXCR4 signaling axis promotes cell survival and proliferation and may contribute to the tropism of leukemia cells towards lymphoid tissues and bone marrow. Therefore, we hypothesized that targeting CXCR4 with an IgG1 antibody, PF-06747143, may constitute an effective therapeutic approach for CLL.MethodsPatient-derived primary CLL-B cells were assessed for cytotoxicity in an in vitro model of CLL microenvironment. PF-06747143 was analyzed for cell death induction and for its potential to interfere with the chemokine CXCL12-induced mechanisms, including migration and F-actin polymerization. PF-06747143 in vivo efficacy was determined in a CLL murine xenograft tumor model.ResultsPF-06747143, a novel-humanized IgG1 CXCR4 antagonist antibody, induced cell death of patient-derived primary CLL-B cells, in presence or absence of stromal cells. Moreover, cell death induction by the antibody was independent of CLL high-risk prognostic markers. The cell death mechanism was dependent on CXCR4 expression, required antibody bivalency, involved reactive oxygen species production, and did not require caspase activation, all characteristics reminiscent of programmed cell death (PCD). PF-06747143 also induced potent B-CLL cytotoxicity via Fc-driven antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity activity (CDC). PF-06747143 had significant combinatorial effect with standard of care (SOC) agents in B-CLL treatment, including rituximab, fludarabine (F-ara-A), ibrutinib, and bendamustine. In a CLL xenograft model, PF-06747143 decreased tumor burden and improved survival as a monotherapy, and in combination with bendamustine.ConclusionsWe show evidence that PF-06747143 has biological activity in CLL primary cells, supporting a rationale for evaluation of PF-06747143 for the treatment of CLL patients

Principles of optical design of the SM beamline at the CLS

Abstract. The spectromicroscopy beamline (SM) at the Canadian Light Source (CLS) will provide 100 -2000 eV photons in a high brightness, high flux, medium resolution and small spot size beam. The beamline consists of an advanced elliptically polarized undulator (EPU) source and a novel entrance slit-less plane grating monochromator which feeds two branch lines, one optimized for scanning transmission X-ray microscopy (STXM), the other for X-ray photoemission electron microscopy (X-PEEM). This article outlines the beamline design strategy, and discusses the design optimization relative to the requirements for state-of-the-art STXM and X-PEEM. DESIGN OBJECTIVES AND CONSTRAINTS Development of third generation SR sources, enhanced quality soft x-ray optics, and advances in beamline design have lead to the construction of several successful spectromicroscopy (SM) facilities around the world [1]. The SM facility at the Canadian Light Source (CLS), a dedicated soft x-ray beamline and associated scanning transmission x-ray microscope (STXM) and x-ray photoemission electron microscope (X-PEEM), will begin operation in 2004. Here we describe the design principles and solutions adopted to optimize the beamline for these two microscopies. There is a substantial difference in image formation for these two techniques. In STXM, the source is demagnified by a Fresnel zone plate (FZP) and the ultimate spatial resolution is defined by the outmost zone width, or ~30nm at current stage of FZP fabrication [2]. To keep such ultimate spot size, the phase accepted by FZP needs to be limited to a single diffraction mode or λ (wavelength of incoming radiation) [3]. As this phase space is much smaller than the emittance of existed SR sources, reduced horizontal phase acceptance can be traded for energy resolving power and overall simplicity. Following the design of the X1A spectromicroscopy beamline at the National Synchrotron Light Source (NSLS), the horizontal dispersing spherical grating monochromator has proved to be a successful choice for several STXM [3][4][5]. In PEEM, the image is formed by magnified projection of low energy photoelectrons with electrostatic or magnetic electron lenses and recorded with a CCD camera. The dominant chromatic aberrations reduce spatial resolution for most PEEM to ~50 nm in the soft x-ray regime. When this spatial resolution is matched to a megapixel high sensitivity CCD the field of view is of order 30-50 µm. Such moderate spot size can be obtained without any phase (source emittance) loss. The figure of merit analysis of different optical schemes was performed by Weiss et al [6] who concluded that a collimated plane grating monochromator is the optimal choice and further, that it allows further beam size reduction if needed . To find the optical scheme which best suits both experiments we compared two design concepts, namely a horizontally dispersed spherical grating monochromator (HD-SGM) and a collimated plane grating monochromator with vertical dispersion (PGM) with primary design goal for highest possible on-sample flux in each microscope, with a resolving power exceeding 3000 and covering the energy range 250-2000eV. The results of the comparison follow by a brief presentation of the optical properties of the PGM-based beamline, which was chosen as a best compromise. The ID10 sector was allocated for the CLS-SM facility, which limits the total length of the beamline to 37m. The lattice parameters (β x =8.5m, β y =4.6m, η x =0.15m, for ε x =18nmrad and assuming 0.2% coupling as projected for 2008 operation) result in electron beam size (FWHM) ∆x=990µ and ∆y=30µ [7]. Chiral molecules, magnetic ordering, sample texture and film orientation are among the scientific topics to be studied so full polarization contro

QED effective action at finite temperature

The QED effective Lagrangian in the presence of an arbitrary constant electromagnetic background field at finite temperature is derived in the imaginary-time formalism to one-loop order. The boundary conditions in imaginary time reduce the set of gauge transformations of the background field, which allows for a further gauge invariant and puts restrictions on the choice of gauge. The additional invariant enters the effective action by a topological mechanism and can be identified with a chemical potential; it is furthermore related to Debye screening. In concordance with the real-time formalism, we do not find a thermal correction to Schwinger's pair-production formula. The calculation is performed on a maximally Lorentz covariant and gauge invariant stage.Comment: 9 pages, REVTeX, 1 figure, typos corrected, references added, final version to appear in Phys. Rev.

Low-Energy Compton Scattering of Polarized Photons on Polarized Nucleons

The general structure of the cross section of $\gamma N$ scattering with polarized photon and/or nucleon in initial and/or final state is systematically described and exposed through invariant amplitudes. A low-energy expansion of the cross section up to and including terms of order $\omega^4$ is given which involves ten structure parameters of the nucleon (dipole, quadrupole, dispersion, and spin polarizabilities). Their physical meaning is discussed in detail. Using fixed-t dispersion relations, predictions for these parameters are obtained and compared with results of chiral perturbation theory. It is emphasized that Compton scattering experiments at large angles can fix the most uncertain of these structure parameters. Predictions for the cross section and double-polarization asymmetries are given and the convergence of the expansion is investigated. The feasibility of the experimental determination of some of the struture parameters is discussed.Comment: 41 pages of text, 9 figures; minor revisions prior to publication in Phys. Rev.

Structure and dynamics of a human myelin protein P2 portal region mutant indicate opening of the β barrel in fatty acid binding proteins

Abstract Background Myelin is a multilayered proteolipid sheath wrapped around selected axons in the nervous system. Its constituent proteins play major roles in forming of the highly regular membrane structure. P2 is a myelin-specific protein of the fatty acid binding protein (FABP) superfamily, which is able to stack lipid bilayers together, and it is a target for mutations in the human inherited neuropathy Charcot-Marie-Tooth disease. A conserved residue that has been proposed to participate in membrane and fatty acid binding and conformational changes in FABPs is Phe57. This residue is thought to be a gatekeeper for the opening of the portal region upon ligand entry and egress. Results We performed a structural characterization of the F57A mutant of human P2. The mutant protein was crystallized in three crystal forms, all of which showed changes in the portal region and helix α2. In addition, the behaviour of the mutant protein upon lipid bilayer binding suggested more unfolding than previously observed for wild-type P2. On the other hand, membrane binding rendered F57A heat-stable, similarly to wild-type P2. Atomistic molecular dynamics simulations showed opening of the side of the discontinuous β barrel, giving important indications on the mechanism of portal region opening and ligand entry into FABPs. The results suggest a central role for Phe57 in regulating the opening of the portal region in human P2 and other FABPs, and the F57A mutation disturbs dynamic cross-correlation networks in the portal region of P2. Conclusions Overall, the F57A variant presents similar properties to the P2 patient mutations recently linked to Charcot-Marie-Tooth disease. Our results identify Phe57 as a residue regulating conformational changes that may accompany membrane surface binding and ligand exchange in P2 and other FABPs