Individual scatterers as microscopic origin of equilibration between spin- polarized edge channels in the quantum Hall regime

The equilibration length between spin-polarized edge states in the Quantum Hall regime is measured as a function of a gate voltage applied to an electrode on top of the edge channels. Reproducible fluctuations in the coupling are observed and interpreted as a mesoscopic fingerprint of single spin-flip scatterers which are turned on and off. A model to analyze macroscopic edge state coupling in terms of individual scatterers is developed, and characteristic values for these scatterers in our samples are extracted. For all samples investigated, the distance between spin-flip scatterers lies between the Drude and the quantum scattering length.Comment: 4 pages, 2 figure

Signals for Lorentz Violation in Post-Newtonian Gravity

The pure-gravity sector of the minimal Standard-Model Extension is studied in the limit of Riemann spacetime. A method is developed to extract the modified Einstein field equations in the limit of small metric fluctuations about the Minkowski vacuum, while allowing for the dynamics of the 20 independent coefficients for Lorentz violation. The linearized effective equations are solved to obtain the post-newtonian metric. The corresponding post-newtonian behavior of a perfect fluid is studied and applied to the gravitating many-body system. Illustrative examples of the methodology are provided using bumblebee models. The implications of the general theoretical results are studied for a variety of existing and proposed gravitational experiments, including lunar and satellite laser ranging, laboratory experiments with gravimeters and torsion pendula, measurements of the spin precession of orbiting gyroscopes, timing studies of signals from binary pulsars, and the classic tests involving the perihelion precession and the time delay of light. For each type of experiment considered, estimates of the attainable sensitivities are provided. Numerous effects of local Lorentz violation can be studied in existing or near-future experiments at sensitivities ranging from parts in 10^4 down to parts in 10^{15}.Comment: 46 pages two-column REVTeX, accepted in Physical Review

Characterization of a POROS\u3csup\u3eTM\u3c/sup\u3e-fumonisin B1 Affinity Column for Isolating Ceramide Synthase from Rat Liver

Fumonisin B1 is a mycotoxin produced by fungi of the genus Fusarium, common pathogens of corn and other grain plants. Toxic effects associated with fumonisin B1 include equine leukoencephalomacia, porcine pulmonary edema, rat renal carcinoma, and murine hepatocellular carcinoma. Increased risk for esophageal cancer in humans has been epidemiologically associated with consumption of corn contaminated with Fusarium, suggesting that fumonisin B1 may be involved. The biological effects of fumonisin B1 exposure result primarily from disruption of de novo sphingolipid biosynthesis via inhibition of ceramide synthase. Exposure of animals or cultured cells to fumonisin B1 results in the characteristic accumulation of sphinganine, a toxic sphingolipid intermediate, concomitant with depletion of essential complex sphingolipids. Ceramide synthase has not been purified to homogeniety and characterized. We prepared crude ceramide synthase from detergent-extracted rat liver homogenates using PEG-precipitation and cation exchange chromatography. Ceramide synthase activity was then sequestered, using fumonisin B1 covalently coupled to POROS-NH particles, and eluted selectively. The observed 119-fold enrichment in specific activity demonstrates the utility of fumonisin-POROS affinity chromatography in the purification of ceramide synthase

Ubiquitin-specific protease-like 1 (USPL1) is a SUMO isopeptidase with essential, non-catalytic functions.

Isopeptidases are essential regulators of protein ubiquitination and sumoylation. However, only two families of SUMO isopeptidases are at present known. Here, we report an activity-based search with the suicide inhibitor haemagglutinin (HA)-SUMO-vinylmethylester that led to the identification of a surprising new SUMO protease, ubiquitin-specific protease-like 1 (USPL1). Indeed, USPL1 neither binds nor cleaves ubiquitin, but is a potent SUMO isopeptidase both in vitro and in cells. C13orf22l—an essential but distant zebrafish homologue of USPL1—also acts on SUMO, indicating functional conservation. We have identified invariant USPL1 residues required for SUMO binding and cleavage. USPL1 is a low-abundance protein that colocalizes with coilin in Cajal bodies. Its depletion does not affect global sumoylation, but causes striking coilin mislocalization and impairs cell proliferation, functions that are not dependent on USPL1 catalytic activity. Thus, USPL1 represents a third type of SUMO protease, with essential functions in Cajal body biology

Concomitant occurrence of EGFR (epidermal growth factor receptor) and KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog) mutations in an ALK (anaplastic lymphoma kinase)-positive lung adenocarcinoma patient with acquired resistance to crizotinib: a case report

BACKGROUND: Anaplastic lymphoma kinase-positive non-small cell lung carcinoma patients are generally highly responsive to the dual anaplastic lymphoma kinase and MET tyrosine kinase inhibitor crizotinib. However, they eventually acquire resistance to this drug, preventing the anaplastic lymphoma kinase inhibitors from having a prolonged beneficial effect. The molecular mechanisms responsible for crizotinib resistance are beginning to emerge, e.g., in some anaplastic lymphoma kinase-positive non-small cell lung carcinomas the development of secondary mutations in this gene has been described. However, the events behind crizotinib-resistance currently remain largely uncharacterized. Thus, we report on an anaplastic lymphoma kinase-positive non-small cell lung carcinoma patient with concomitant occurrence of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations upon development of crizotinib-resistance. CASE PRESENTATION: A 61-year-old Caucasian never-smoking male was diagnosed with anaplastic lymphoma kinase -positive pulmonary adenocarcinoma, stage T4N3M1b. Treatment with crizotinib initially resulted in complete objective response in the thorax and partial response in the abdomen, but after 8 months of therapy the patient acquired resistance and progressed. Biopsies from new metastases revealed development of epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog mutations concomitant with the original anaplastic lymphoma kinase gene rearrangement and without signs of anaplastic lymphoma kinase fusion gene amplification or secondary anaplastic lymphoma kinase mutations. CONCLUSION: To our knowledge, this is the first report of an anaplastic lymphoma kinase-positive pulmonary adenocarcinoma, which upon emergence of crizotinib resistance acquired 2 new somatic mutations in the epidermal growth factor receptor and V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog genes, respectively, concomitant with the original anaplastic lymphoma kinase rearrangement. Thus, these 3 driver mutations, usually considered mutually exclusive, may coexist in advanced non-small cell lung carcinoma that becomes resistant to crizotinib, presumably because heterogeneous tumor clones utilize epidermal growth factor receptor and/or V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog signaling to circumvent the inhibition of anaplastic lymphoma kinase-mediated signaling by crizotinib. The identification of new targetable somatic mutations by tumor re-biopsy may help clarify the mechanism behind the development of the acquired crizotinib resistance and pave the way for combined strategies involving multiple targeted therapies

Euclid preparation -XIX. Impact of magnification on photometric galaxy clustering

Aims. We investigate the importance of lensing magnification for estimates of galaxy clustering and its cross-correlation with shear for the photometric sample of Euclid. Using updated specifications, we study the impact of lensing magnification on the constraints and the shift in the estimation of the best fitting cosmological parameters that we expect if this effect is neglected. Methods. We follow the prescriptions of the official Euclid Fisher matrix forecast for the photometric galaxy clustering analysis and the combination of photometric clustering and cosmic shear. The slope of the luminosity function (local count slope), which regulates the amplitude of the lensing magnification, and the galaxy bias have been estimated from the Euclid Flagship simulation. Results. We find that magnification significantly affects both the best-fit estimation of cosmological parameters and the constraints in the galaxy clustering analysis of the photometric sample. In particular, including magnification in the analysis reduces the 1σ errors on Ωm, 0, w0, wa at the level of 20–35%, depending on how well we will be able to independently measure the local count slope. In addition, we find that neglecting magnification in the clustering analysis leads to shifts of up to 1.6σ in the best-fit parameters. In the joint analysis of galaxy clustering, cosmic shear, and galaxy–galaxy lensing, magnification does not improve precision, but it leads to an up to 6σ bias if neglected. Therefore, for all models considered in this work, magnification has to be included in the analysis of galaxy clustering and its cross-correlation with the shear signal (3 × 2pt analysis) for an accurate parameter estimation. Key words: large-scale structure of Universe / cosmological parameters / cosmology: theor

Changing distributions of sea ice melt and meteoric water west of the Antarctic Peninsula

The Western Antarctic Peninsula has recently undergone rapid climatic warming, with associated decreases in sea ice extent and duration, and increases in precipitation and glacial discharge to the ocean. These shifts in the freshwater budget can have significant consequences on the functioning of the regional ecosystem, feedbacks on regional climate, and sea-level rise. Here we use shelf-wide oxygen isotope data from cruises in four consecutive Januaries (2011–2014) to distinguish the freshwater input from sea ice melt separately from that due to meteoric sources (precipitation plus glacial discharge). Sea ice melt distributions varied from minima in 2011 of around 0 % up to maxima in 2014 of around 4–5%. Meteoric water contribution to the marine environment is typically elevated inshore, due to local glacial discharge and orographic effects on precipitation, but this enhanced contribution was largely absent in January 2013 due to anomalously low precipitation in the last quarter of 2012. Both sea ice melt and meteoric water changes are seen to be strongly influenced by changes in regional wind forcing associated with the Southern Annular Mode and the El Niño–Southern Oscillation phenomenon, which also impact on net sea ice motion as inferred from the isotope data. A near-coastal time series of isotope data collected from Rothera Research Station reproduces well the temporal pattern of changes in sea ice melt, but less well the meteoric water changes, due to local glacial inputs and precipitation effects

CLASH-VLT: A Highly Precise Strong Lensing Model of the Galaxy Cluster RXC J2248.7-4431 (Abell S1063) and Prospects for Cosmography

We perform a comprehensive study of the total mass distribution of the galaxy cluster RXCJ2248 ($z=0.348$) with a set of high-precision strong lensing models, which take advantage of extensive spectroscopic information on many multiply lensed systems. In the effort to understand and quantify inherent systematics in parametric strong lensing modelling, we explore a collection of 22 models where we use different samples of multiple image families, parametrizations of the mass distribution and cosmological parameters. As input information for the strong lensing models, we use the CLASH HST imaging data and spectroscopic follow-up observations, carried out with the VIMOS and MUSE spectrographs, to identify bona-fide multiple images. A total of 16 background sources, over the redshift range $1.0-6.1$, are multiply lensed into 47 images, 24 of which are spectroscopically confirmed and belong to 10 individual sources. The cluster total mass distribution and underlying cosmology in the models are optimized by matching the observed positions of the multiple images on the lens plane. We show that with a careful selection of a sample of spectroscopically confirmed multiple images, the best-fit model reproduces their observed positions with a rms of $0.3$ in a fixed flat $\Lambda$CDM cosmology, whereas the lack of spectroscopic information lead to biases in the values of the model parameters. Allowing cosmological parameters to vary together with the cluster parameters, we find (at $68\%$ confidence level) $\Omega_m=0.25^{+0.13}_{-0.16}$ and $w=-1.07^{+0.16}_{-0.42}$ for a flat $\Lambda$CDM model, and $\Omega_m=0.31^{+0.12}_{-0.13}$ and $\Omega_\Lambda=0.38^{+0.38}_{-0.27}$ for a universe with $w=-1$ and free curvature. Using toy models mimicking the overall configuration of RXCJ2248, we estimate the impact of the line of sight mass structure on the positional rms to be $0.3\pm 0.1$.(ABRIDGED)Comment: 23 pages, 13 figures, accepted for publication in A&

CLASH: Extending galaxy strong lensing to small physical scales with distant sources highly-magnified by galaxy cluster members

We present a strong lensing system in which a double source is imaged 5 times by 2 early-type galaxies. We take advantage in this target of the multi-band photometry obtained as part of the CLASH program, complemented by the spectroscopic data of the VLT/VIMOS and FORS2 follow-up campaign. We use a photometric redshift of 3.7 for the source and confirm spectroscopically the membership of the 2 lenses to the galaxy cluster MACS J1206.2-0847 at redshift 0.44. We exploit the excellent angular resolution of the HST/ACS images to model the 2 lenses in terms of singular isothermal sphere profiles and derive robust effective velocity dispersions of (97 +/- 3) and (240 +/- 6) km/s. The total mass distribution of the cluster is also well characterized by using only the local information contained in this lensing system, that is located at a projected distance of more than 300 kpc from the cluster luminosity center. According to our best-fitting lensing and composite stellar population models, the source is magnified by a total factor of 50 and has a luminous mass of about (1.0 +/- 0.5) x 10^{9} M_{Sun}. By combining the total and luminous mass estimates of the 2 lenses, we measure luminous over total mass fractions projected within the effective radii of 0.51 +/- 0.21 and 0.80 +/- 0.32. With these lenses we can extend the analysis of the mass properties of lens early-type galaxies by factors that are about 2 and 3 times smaller than previously done with regard to, respectively, velocity dispersion and luminous mass. The comparison of the total and luminous quantities of our lenses with those of astrophysical objects with different physical scales reveals the potential of studies of this kind for investigating the internal structure of galaxies. These studies, made possible thanks to the CLASH survey, will allow us to go beyond the current limits posed by the available lens samples in the field.Comment: 20 pages, 10 figures, accepted for publication in the Astrophysical Journa

A Census of Star-Forming Galaxies in the z~9-10 Universe based on HST+Spitzer Observations Over 19 CLASH clusters: Three Candidate z~9-10 Galaxies and Improved Constraints on the Star Formation Rate Density at z~9

We utilise a two-color Lyman-Break selection criterion to search for z~9-10 galaxies over the first 19 clusters in the CLASH program. A systematic search yields three z~9-10 candidates. While we have already reported the most robust of these candidates, MACS1149-JD, two additional z~9 candidates are also found and have H_{160}-band magnitudes of ~26.2-26.9. A careful assessment of various sources of contamination suggests <~1 contaminants for our z~9-10 selection. To determine the implications of these search results for the LF and SFR density at z~9, we introduce a new differential approach to deriving these quantities in lensing fields. Our procedure is to derive the evolution by comparing the number of z~9-10 galaxy candidates found in CLASH with the number of galaxies in a slightly lower redshift sample (after correcting for the differences in selection volumes), here taken to be z~8. This procedure takes advantage of the fact that the relative volumes available for the z~8 and z~9-10 selections behind lensing clusters are not greatly dependent on the details of the lensing models. We find that the normalization of the UV LF at z~9 is just 0.28_{-0.20}^{+0.39}\times that at z~8, ~1.4_{-0.8}^{+3.0}x lower than extrapolating z~4-8 LF results. While consistent with the evolution in the UV LF seen at z~4-8, these results marginally favor a more rapid evolution at z>8. Compared to similar evolutionary findings from the HUDF, our result is less insensitive to large-scale structure uncertainties, given our many independent sightlines on the high-redshift universe.Comment: 22 pages, 11 figures, 5 tables, accepted for publication in the Astrophysical Journal, updated to include the much deeper Spitzer/IRAC observations over our three z~9-10 candidate