Infrared microspectroscopy to elucidate the underlying biomolecular mechanisms of FLASH radiotherapy.

FLASH-radiotherapy (FLASH-RT) is an emerging modality that uses ultra-high dose rates of radiation to enable curative doses to the tumor while preserving normal tissue. The biological studies showed the potential of FLASH-RT to revolutionize radiotherapy cancer treatments. However, the complex biological basis of FLASH-RT is not fully known yet. Within this context, our aim is to get deeper insights into the biomolecular mechanisms underlying FLASH-RT through Fourier Transform Infrared Microspectroscopy (FTIRM). C57Bl/6J female mice were whole brain irradiated at 10 Gy with the eRT6-Oriatron system. 10 Gy FLASH-RT was delivered in 1 pulse of 1.8μs and conventional irradiations at 0.1 Gy/s. Brains were sampled and prepared for analysis 24 h post-RT. FTIRM was performed at the MIRAS beamline of ALBA Synchrotron. Infrared raster scanning maps of the whole mice brain sections were collected for each sample condition. Hyperspectral imaging and Principal Component Analysis (PCA) were performed in several regions of the brain. PCA results evidenced a clear separation between conventional and FLASH irradiations in the 1800-950 cm <sup>-1</sup> region, with a significant overlap between FLASH and Control groups. An analysis of the loading plots revealed that most of the variance accounting for the separation between groups was associated to modifications in the protein backbone (Amide I). This protein degradation and/or conformational rearrangement was concomitant with nucleic acid fragmentation/condensation. Cluster separation between FLASH and conventional groups was also present in the 3000-2800 cm <sup>-1</sup> region, being correlated with changes in the methylene and methyl group concentrations and in the lipid chain length. Specific vibrational features were detected as a function of the brain region. This work provided new insights into the biomolecular effects involved in FLASH-RT through FTIRM. Our results showed that beyond nucleic acid investigations, one should take into account other dose-rate responsive molecules such as proteins, as they might be key to understand FLASH effect

Time transfer and frequency shift to the order 1/c^4 in the field of an axisymmetric rotating body

Within the weak-field, post-Newtonian approximation of the metric theories of gravity, we determine the one-way time transfer up to the order 1/c^4, the unperturbed term being of order 1/c, and the frequency shift up to the order 1/c^4. We adapt the method of the world-function developed by Synge to the Nordtvedt-Will PPN formalism. We get an integral expression for the world-function up to the order 1/c^3 and we apply this result to the field of an isolated, axisymmetric rotating body. We give a new procedure enabling to calculate the influence of the mass and spin multipole moments of the body on the time transfer and the frequency shift up to the order 1/c^4. We obtain explicit formulas for the contributions of the mass, of the quadrupole moment and of the intrinsic angular momentum. In the case where the only PPN parameters different from zero are beta and gamma, we deduce from these results the complete expression of the frequency shift up to the order 1/c^4. We briefly discuss the influence of the quadrupole moment and of the rotation of the Earth on the frequency shifts in the ACES mission.Comment: 17 pages, no figure. Version 2. Abstract and Section II revised. To appear in Physical Review

Thixotropy in macroscopic suspensions of spheres

An experimental study of the viscosity of a macroscopic suspension, i.e. a suspension for which Brownian motion can be neglected, under steady shear is presented. The suspension is prepared with a high packing fraction and is density-matched in a Newtonian carrier fluid. The viscosity of the suspension depends on the shear rate and the time of shearing. It is shown for the first time that a macroscopic suspension shows thixotropic viscosity, i.e. shear-thinning with a long relaxation time as a unique function of shear. The relaxation times show a systematic decrease with increasing shear rate. These relaxation times are larger when decreasing the shear rates, compared to those observed after increasing the shear. The time scales involved are about 10000 times larger than the viscous time scale and about 1000 times smaller than the thermodynamic time scale. The structure of the suspension at the outer cylinder of a viscometer is monitored with a camera, showing the formation of a hexagonal structure. The temporal decrease of the viscosity under shear coincides with the formation of this hexagonal pattern

Antitumor Effect by Either FLASH or Conventional Dose Rate Irradiation Involves Equivalent Immune Responses.

The capability of ultrahigh dose rate FLASH radiation therapy to generate the FLASH effect has opened the possibility to enhance the therapeutic index of radiation therapy. The contribution of the immune response has frequently been hypothesized to account for a certain fraction of the antitumor efficacy and tumor kill of FLASH but has yet to be rigorously evaluated. To investigate the immune response as a potentially important mechanism of the antitumor effect of FLASH, various murine tumor models were grafted either subcutaneously or orthotopically into immunocompetent mice or in moderately and severely immunocompromised mice. Mice were locally irradiated with single dose (20 Gy) or hypofractionated regimens (3 × 8 or 2 × 6 Gy) using FLASH (≥2000 Gy/s) and conventional (CONV) dose rates (0.1 Gy/s), with/without anti-CTLA-4. Tumor growth was monitored over time and immune profiling performed. FLASH and CONV 20 Gy were isoeffective in delaying tumor growth in immunocompetent and moderately immunodeficient hosts and increased tumor doubling time to >14 days versus >7 days in control animals. Similar observations were obtained with a hypofractionated scheme, regardless of the microenvironment (subcutaneous flank vs ortho lungs). Interestingly, in profoundly immunocompromised mice, 20 Gy FLASH retained antitumor activity and significantly increased tumor doubling time to >14 days versus >8 days in control animals, suggesting a possible antitumor mechanism independent of the immune response. Analysis of the tumor microenvironment showed similar immune profiles after both irradiation modalities with significant decrease of lymphoid cells by ∼40% and a corresponding increase of myeloid cells. In addition, FLASH and CONV did not increase transforming growth factor-β1 levels in tumors compared with unirradiated control animals. Furthermore, when a complete and long-lasting antitumor response was obtained (>140 days), both modalities of irradiation were able to generate a long-term immunologic memory response. The present results clearly document that the tumor responses across multiple immunocompetent and immunodeficient mouse models are largely dose rate independent and simultaneously contradict a major role of the immune response in the antitumor efficacy of FLASH. Therefore, our study indicates that FLASH is as potent as CONV in modulating antitumor immune response and can be used as an immunomodulatory agent

Middle pleistocene glaciation in Patagonia dated by cosmogenic-nuclide measurements on outwash gravels

The well-preserved glacial record in Argentine Patagonia offers a ~ 1 Ma archive of terrestrial climate extremes in southern South America. These glacial deposits remain largely undated beyond the range of radiocarbon dating at ca. 40 ka. Dating old glacial deposits (> several 105 a) by cosmogenic surface exposure methods is problematic because of the uncertainty in moraine degradation and boulder erosion rates. Here, we show that cobbles on outwash terraces can reliably date ‘old’ glacial deposits in the Lago Pueyrredón valley, 47.5° S, Argentina. Favorable environmental conditions (e.g., aridity and strong winds) have enabled continuous surface exposure of cobbles and preservation of outwash terraces. The data demonstrate that nuclide inheritance is negligible and we therefore use the oldest surface cobbles to date the deposit. 10Be concentrations in outwash cobbles reveal a major glacial advance at ca. 260 ka, concurrent with Marine Isotope Stage 8 (MIS 8) and dust peaks in Antarctic ice cores. A 10Be concentration depth-profile in the outwash terrace supports the age and suggests a low terrace erosion rate of ca. 0.5 mm ka− 1. We compare these data to exposure ages obtained from associated moraines and find that surface boulders underestimate the age of the glaciation by ~ 100 ka; thus the oldest boulders in this area do not date closely moraine deposition. The 10Be concentration in moraine cobbles help to constrain moraine degradation rates. These data together with constraints from measured 26Al/10Be ratios suggest that all moraine boulders were likely exhumed after original deposition. We determine the local Last Glacial Maximum (LGM) occurred at ~ 27–25 ka, consistent with the maximum LGM in other parts of Patagonia

Atmospheric Heating and Wind Acceleration: Results for Cool Evolved Stars based on Proposed Processes

A chromosphere is a universal attribute of stars of spectral type later than ~F5. Evolved (K and M) giants and supergiants (including the zeta Aurigae binaries) show extended and highly turbulent chromospheres, which develop into slow massive winds. The associated continuous mass loss has a significant impact on stellar evolution, and thence on the chemical evolution of galaxies. Yet despite the fundamental importance of those winds in astrophysics, the question of their origin(s) remains unsolved. What sources heat a chromosphere? What is the role of the chromosphere in the formation of stellar winds? This chapter provides a review of the observational requirements and theoretical approaches for modeling chromospheric heating and the acceleration of winds in single cool, evolved stars and in eclipsing binary stars, including physical models that have recently been proposed. It describes the successes that have been achieved so far by invoking acoustic and MHD waves to provide a physical description of plasma heating and wind acceleration, and discusses the challenges that still remain.Comment: 46 pages, 9 figures, 1 table; modified and unedited manuscript; accepted version to appear in: Giants of Eclipse, eds. E. Griffin and T. Ake (Berlin: Springer

Dispersion of Ordered Stripe Phases in the Cuprates

A phase separation model is presented for the stripe phase of the cuprates, which allows the doping dependence of the photoemission spectra to be calculated. The idealized limit of a well-ordered array of magnetic and charged stripes is analyzed, including effects of long-range Coulomb repulsion. Remarkably, down to the limit of two-cell wide stripes, the dispersion can be interpreted as essentially a superposition of the two end-phase dispersions, with superposed minigaps associated with the lattice periodicity. The largest minigap falls near the Fermi level; it can be enhanced by proximity to a (bulk) Van Hove singularity. The calculated spectra are dominated by two features -- this charge stripe minigap plus the magnetic stripe Hubbard gap. There is a strong correlation between these two features and the experimental photoemission results of a two-peak dispersion in La$_{2-x}$Sr$_x$CuO$_4$, and the peak-dip-hump spectra in Bi$_2$Sr$_2$CaCu$_2$O$_{8+\delta}$. The differences are suggestive of the role of increasing stripe fluctuations. The 1/8 anomaly is associated with a quantum critical point, here expressed as a percolation-like crossover. A model is proposed for the limiting minority magnetic phase as an isolated two-leg ladder.Comment: 24 pages, 26 PS figure

Magnetic Field Generation in Stars

Enormous progress has been made on observing stellar magnetism in stars from the main sequence through to compact objects. Recent data have thrown into sharper relief the vexed question of the origin of stellar magnetic fields, which remains one of the main unanswered questions in astrophysics. In this chapter we review recent work in this area of research. In particular, we look at the fossil field hypothesis which links magnetism in compact stars to magnetism in main sequence and pre-main sequence stars and we consider why its feasibility has now been questioned particularly in the context of highly magnetic white dwarfs. We also review the fossil versus dynamo debate in the context of neutron stars and the roles played by key physical processes such as buoyancy, helicity, and superfluid turbulence,in the generation and stability of neutron star fields. Independent information on the internal magnetic field of neutron stars will come from future gravitational wave detections. Thus we maybe at the dawn of a new era of exciting discoveries in compact star magnetism driven by the opening of a new, non-electromagnetic observational window. We also review recent advances in the theory and computation of magnetohydrodynamic turbulence as it applies to stellar magnetism and dynamo theory. These advances offer insight into the action of stellar dynamos as well as processes whichcontrol the diffusive magnetic flux transport in stars.Comment: 41 pages, 7 figures. Invited review chapter on on magnetic field generation in stars to appear in Space Science Reviews, Springe

Measurement of the polarisation of W bosons produced with large transverse momentum in pp collisions at sqrt(s) = 7 TeV with the ATLAS experiment

This paper describes an analysis of the angular distribution of W->enu and W->munu decays, using data from pp collisions at sqrt(s) = 7 TeV recorded with the ATLAS detector at the LHC in 2010, corresponding to an integrated luminosity of about 35 pb^-1. Using the decay lepton transverse momentum and the missing transverse energy, the W decay angular distribution projected onto the transverse plane is obtained and analysed in terms of helicity fractions f0, fL and fR over two ranges of W transverse momentum (ptw): 35 < ptw < 50 GeV and ptw > 50 GeV. Good agreement is found with theoretical predictions. For ptw > 50 GeV, the values of f0 and fL-fR, averaged over charge and lepton flavour, are measured to be : f0 = 0.127 +/- 0.030 +/- 0.108 and fL-fR = 0.252 +/- 0.017 +/- 0.030, where the first uncertainties are statistical, and the second include all systematic effects.Comment: 19 pages plus author list (34 pages total), 9 figures, 11 tables, revised author list, matches European Journal of Physics C versio

Observation of a new chi_b state in radiative transitions to Upsilon(1S) and Upsilon(2S) at ATLAS

The chi_b(nP) quarkonium states are produced in proton-proton collisions at the Large Hadron Collider (LHC) at sqrt(s) = 7 TeV and recorded by the ATLAS detector. Using a data sample corresponding to an integrated luminosity of 4.4 fb^-1, these states are reconstructed through their radiative decays to Upsilon(1S,2S) with Upsilon->mu+mu-. In addition to the mass peaks corresponding to the decay modes chi_b(1P,2P)->Upsilon(1S)gamma, a new structure centered at a mass of 10.530+/-0.005 (stat.)+/-0.009 (syst.) GeV is also observed, in both the Upsilon(1S)gamma and Upsilon(2S)gamma decay modes. This is interpreted as the chi_b(3P) system.Comment: 5 pages plus author list (18 pages total), 2 figures, 1 table, corrected author list, matches final version in Physical Review Letter