"Re-educating" tumor-associated macrophages by targeting NF-kappaB

The nuclear factor kappaB (NF-kappaB) signaling pathway is important in cancer-related inflammation and malignant progression. Here, we describe a new role for NF-kappaB in cancer in maintaining the immunosuppressive phenotype of tumor-associated macrophages (TAMs). We show that macrophages are polarized via interleukin (IL)-1R and MyD88 to an immunosuppressive "alternative" phenotype that requires IkappaB kinase beta-mediated NF-kappaB activation. When NF-kappaB signaling is inhibited specifically in TAMs, they become cytotoxic to tumor cells and switch to a "classically" activated phenotype; IL-12(high), major histocompatibility complex II(high), but IL-10(low) and arginase-1(low). Targeting NF-kappaB signaling in TAMs also promotes regression of advanced tumors in vivo by induction of macrophage tumoricidal activity and activation of antitumor activity through IL-12-dependent NK cell recruitment. We provide a rationale for manipulating the phenotype of the abundant macrophage population already located within the tumor microenvironment; the potential to "re-educate" the tumor-promoting macrophage population may prove an effective and novel therapeutic approach for cancer that complements existing therapies

Polo like kinase 2 tumour suppressor and cancer biomarker: new perspectives on drug sensitivity/resistance in ovarian cancer

The polo-like kinase PLK2 has recently been identified as a potential theranostic marker in the management of chemotherapy sensitive cancers. The methylation status of the PLK2 CpG island varies with sensitivity to paclitaxel and platinum in ovarian cancer cell lines. Importantly, extrapolation of these in vitro data to the clinical setting confirms that the methylation status of the PLK2 CpG island predicts outcomes in patients treated with carboplatin and paclitaxel chemotherapy. A second cell cycle regulator, p57Kip2, is also subject to epigenetic silencing in carboplatin resistance in vitro and in vivo, emphasising that cell cycle regulators are important determinants of sensitivity to chemotherapeutic agents and providing insights into the phenomenon of collateral drug sensitivity in oncology. Understanding the mechanistic basis and identification of robust biomarkers to predict collateral sensitivity may inform optimal use of chemotherapy in patients receiving multiple lines of treatment

Quasiparticle Breakdown and Spin Hamiltonian of the Frustrated Quantum Pyrochlore Yb2_2Ti2_2O7_7 in Magnetic Field

The frustrated pyrochlore magnet Yb$_2$Ti$_2$O$_7$ has the remarkable property that it orders magnetically, but has no propagating magnons over wide regions of the Brillouin zone. Here we use inelastic neutron scattering to follow how the spectrum evolves in cubic-axis magnetic fields. At high fields we observe in addition to dispersive magnons also a two-magnon continuum, which grows in intensity upon reducing the field and overlaps with the one-magnon states at intermediate fields leading to strong renormalization of the dispersion relations, and magnon decays. Using heat capacity measurements we find that the low and high field regions are smoothly connected with no sharp phase transition, with the spin gap increasing monotonically in field. Through fits to an extensive data set we re-evaluate the spin Hamiltonian finding dominant quantum exchange terms, which we propose are responsible for the anomalously strong fluctuations and quasiparticle breakdown effects observed at low fields.Comment: 5 pages main text + 19 pages supplemental materia

Do the fundamental constants change with time ?

Comparisons between the redshifts of spectral lines from cosmologically-distant galaxies can be used to probe temporal changes in low-energy fundamental constants like the fine structure constant and the proton-electron mass ratio. In this article, I review the results from, and the advantages and disadvantages of, the best techniques using this approach, before focussing on a new method, based on conjugate satellite OH lines, that appears to be less affected by systematic effects and hence holds much promise for the future.Comment: 15 pages, 3 figures. This is an electronic version of an invited review article for Mod. Phys. Lett. A, published as [Mod. Phys. Lett. A, Vol. 23, No. 32, 2008, pp. 2711] (copyright World Scientific Publishing Company; http://www.worldscientific.com/

Optical constraints of kerogen from 0.15 to 40 microns: Comparison with meteoritic organics

Kerogens are dark, complex organic materials produced on the Earth primarily by geologic processing of biologic materials, but kerogens have chemical and spectral similarities to some classes of highly processed extraterrestrial organic materials. Kerogen-like solids were proposed as constitutents of the very dark reddish surfaces of some asteroids and are also spectrally similar to some carbonaceous organic residues and the Iapetus dark material. Kerogen can thus serve as a useful laboratory analog to very dark, spectrally red extraterrestrial materials; its optical constants can be used to investigate the effects of particle size, void space and mixing of bright and dark components in models of scattering by dark asteroidal, cometary, and satellite surfaces. Measurements of the optical constants of both Type 2 kerogen and of macromolecular organic residue from the Murchison carbonaceous chondrite via transmission and reflection measurements on thin films are reported. The real part of the refractive index, n, is determined by variable incidence-angle reflectance to be 1.60 + or - 0.05 from 0.4 to 2.0 micrometers wavelength. Work extending the measurement of n to longer wavelengths is in progress. The imaginary part of the refractive index, k, shows substantial structure from 0.15 to 40 micrometers. The values are accurate to + or - 20 percent in the UV and IR regions and to + or - 30 percent in the visible. The k values of organic residues were also measured from the Murchison meteorite. Comparison of the kerogen and Murchison data reveals that between 0.15 and 40 microns, Murchison has a similar structure but no bands as sharp as in kerogen, and that the k values for Murchison are significantly higher than those of kerogen

Excitations in the quantum paramagnetic phase of the quasi-one-dimensional Ising magnet CoNb2_2O6_6 in a transverse field: Geometric frustration and quantum renormalization effects

The quasi-one-dimensional (1D) Ising ferromagnet CoNb$_2$O$_6$ has recently been driven via applied transverse magnetic fields through a continuous quantum phase transition from spontaneous magnetic order to a quantum paramagnet, and dramatic changes were observed in the spin dynamics, characteristic of weakly perturbed 1D Ising quantum criticality. We report here extensive single-crystal inelastic neutron scattering measurements of the magnetic excitations throughout the three-dimensional (3D) Brillouin zone in the quantum paramagnetic phase just above the critical field to characterize the effects of the finite interchain couplings. In this phase, we observe that excitations have a sharp, resolution-limited line shape at low energies and over most of the dispersion bandwidth, as expected for spin-flip quasiparticles. We map the full bandwidth along the strongly dispersive chain direction and resolve clear modulations of the dispersions in the plane normal to the chains, characteristic of frustrated interchain couplings in an antiferromagnetic isosceles triangular lattice. The dispersions can be well parametrized using a linear spin-wave model that includes interchain couplings and further neighbor exchanges. The observed dispersion bandwidth along the chain direction is smaller than that predicted by a linear spin-wave model using exchange values determined at zero field, and this effect is attributed to quantum renormalization of the dispersion beyond the spin-wave approximation in fields slightly above the critical field, where quantum fluctuations are still significant.Comment: 11 pages, 6 figures. Updated references. Minor changes to text and figure

Instability Heating of Sympathetically-Cooled Ions in a Linear Paul Trap

Sympathetic laser cooling of ions stored within a linear-geometry, radio frequency, electric-quadrupole trap has been investigated using computational and theoretical techniques. The simulation, which allows 5 sample ions to interact with 35 laser-cooled atomic ions, revealed an instability heating mechanism, which can prevent ions below a certain critical mass from being sympathetically cooled. This critical mass can however be varied by changing the trapping field parameters thus allowing ions with a very large range of masses to be sympathetically cooled using a single ion species. A theoretical explanation of this instability heating mechanism is presented which predicts that the cooling-heating boundary in trapping parameter space is a line of constant $q_u$ (ion trap stability coefficient), a result supported by the computational results. The threshold value of $q_u$ depends on the masses of the interacting ions. A functional form of this dependence is given

Opportunities for financing sustainable development using complementary local currencies

Financing building retrofit projects that contribute to climate change mitigation has always represented a significant barrier. With 28% of global emissions coming from existing buildings, it is of paramount importance to carry out retrofit measures that lead to significant reduction of these emissions. Whilst this is perfectly possible to achieve with current methods and current technology, there is no sufficient conventional finance to carry out zero carbon retrofit at scale required for climate change mitigation. The article introduces an alternative and sustainable business model that creates new opportunities for financing zero carbon retrofit of buildings. It demonstrates that the value of solar energy falling on roofs of buildings can become a driver for new local economic systems, and discusses the requirements for practical application.Peer reviewedFinal Published versio

The Clusters AgeS Experiment (CASE). I. V209 omega Cen - An Eclipsing Post-Common Envelope Binary in the Globular Cluster omega Cen

We use photometric and spectroscopic observations of the detached eclipsing binary V209 omega Cen to derive the masses, radii, and luminosities of the component stars. The system exhibits total eclipses and, based on the measured systemic velocity and the derived distance, is a member of the globular cluster omega Cen. We obtain 0.945 +/- 0.043 Msun, 0.983 +/- 0.015 Rsun and 6.68 +/- 0.88 Lsun for the cooler, but larger and more luminous primary component. The secondary component has 0.144 +/- 0.008 Msun, 0.425 +/- 0.008 Rsun and 2.26 +/- 0.28 Lsun. The effective temperatures are estimated at 9370 K for the primary and at 10866 K for the secondary. On the color-magnitude diagram of the cluster, the primary component occupies a position between the tip of the blue straggler region and the extended horizontal branch while the secondary component is located close to the red border of the area occupied by hot subdwarfs. However, its radius is too large and its effective temperature is too low for it to be an sdB star. We propose a scenario leading to the formation of a system with such unusual properties with the primary component ``re-born'' from a former white dwarf which accreted a new envelope through mass transfer from its companion. The secondary star has lost most of its envelope while starting its ascent onto the sub-giant branch. It failed to ignite helium in its core and is currently powered by a hydrogen burning shell.Comment: 24 pages, 9 figures, AJ, in pres

Spatial Structure of Ion Beams in an Expanding Plasma

We report spatially resolved perpendicular and parallel, to the magnetic field, ion velocity distribution function (IVDF) measurements in an expanding argon helicon plasma. The parallel IVDFs, obtained through laser induced fluorescence (LIF), show an ion beam with v ≈ 8000 m/s flowing downstream and confined to the center of the discharge. The ion beam is measurable for tens of centimeters along the expansion axis before the LIF signal fades, likely a result of metastable quenching of the beam ions. The parallel ion beam velocity slows in agreement with expectations for the measured parallel electric field. The perpendicular IVDFs show an ion population with a radially outward flow that increases with distance from the plasma axis. Structures aligned to the expanding magnetic field appear in the DC electric field, the electron temperature, and the plasma density in the plasma plume. These measurements demonstrate that at least two-dimensional and perhaps fully three-dimensional models are needed to accurately describe the spontaneous acceleration of ion beams in expanding plasmas