Comment on "Scaling of atmosphere and ocean temperature correlations in observations and climate models"

In a recent letter [K. Fraedrich and R. Blender, Phys. Rev. Lett. 90, 108501 (2003)], Fraedrich and Blender studied the scaling of atmosphere and ocean temperature. They analyzed the fluctuation functions F(s) ~ s^alpha of monthly temperature records (mostly from grid data) by using the detrended fluctuation analysis (DFA2) and claim that the scaling exponent alpha over the inner continents is equal to 0.5, being characteristic of uncorrelated random sequences. Here we show that this statement is (i) not supported by their own analysis and (ii) disagrees with the analysis of the daily observational data from which the grid monthly data have been derived. We conclude that also for the inner continents, the exponent is between 0.6 and 0.7, similar as for the coastline-stations.Comment: 1 page with 2 figure

Design considerations for table-top, laser-based VUV and X-ray free electron lasers

A recent breakthrough in laser-plasma accelerators, based upon ultrashort high-intensity lasers, demonstrated the generation of quasi-monoenergetic GeV-electrons. With future Petawatt lasers ultra-high beam currents of ~100 kA in ~10 fs can be expected, allowing for drastic reduction in the undulator length of free-electron-lasers (FELs). We present a discussion of the key aspects of a table-top FEL design, including energy loss and chirps induced by space-charge and wakefields. These effects become important for an optimized table-top FEL operation. A first proof-of-principle VUV case is considered as well as a table-top X-ray-FEL which may open a brilliant light source also for new ways in clinical diagnostics.Comment: 6 pages, 4 figures; accepted for publication in Appl. Phys.

Weak lensing analysis of RXC J2248.7-4431

We present a weak lensing analysis of the cluster of galaxies RXC J2248.7-4431, a massive system at z=0.3475 with prominent strong lensing features covered by the HST/CLASH survey (Postman et al. 2012). Based on UBVRIZ imaging from the WFI camera at the MPG/ESO-2.2m telescope, we measure photometric redshifts and shapes of background galaxies. The cluster is detected as a mass peak at 5sigma significance. Its density can be parametrised as an NFW profile (Navarro et al. 1996) with two free parameters, the mass M_200m=(33.1+9.6-6.8)x10^14Msol and concentration c_200m=2.6+1.5-1.0. We discover a second cluster inside the field of view at a photometric redshift of z~0.6, with an NFW mass of M_200m=(4.0+3.7-2.6)x10^14Msol.Comment: 15 pages, 17 figures; matching published versio

Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models.

Continuous de novo fatty acid synthesis is a common feature of cancer that is required to meet the biosynthetic demands of a growing tumor. This process is controlled by the rate-limiting enzyme acetyl-CoA carboxylase (ACC), an attractive but traditionally intractable drug target. Here we provide genetic and pharmacological evidence that in preclinical models ACC is required to maintain the de novo fatty acid synthesis needed for growth and viability of non-small-cell lung cancer (NSCLC) cells. We describe the ability of ND-646-an allosteric inhibitor of the ACC enzymes ACC1 and ACC2 that prevents ACC subunit dimerization-to suppress fatty acid synthesis in vitro and in vivo. Chronic ND-646 treatment of xenograft and genetically engineered mouse models of NSCLC inhibited tumor growth. When administered as a single agent or in combination with the standard-of-care drug carboplatin, ND-646 markedly suppressed lung tumor growth in the Kras;Trp53-/- (also known as KRAS p53) and Kras;Stk11-/- (also known as KRAS Lkb1) mouse models of NSCLC. These findings demonstrate that ACC mediates a metabolic liability of NSCLC and that ACC inhibition by ND-646 is detrimental to NSCLC growth, supporting further examination of the use of ACC inhibitors in oncology

Power-law persistence and trends in the atmosphere: A detailed study of long temperature records

We use several variants of the detrended fluctuation analysis to study the appearance of long-term persistence in temperature records, obtained at 95 stations all over the globe. Our results basically confirm earlier studies. We find that the persistence, characterized by the correlation C(s) of temperature variations separated by s days, decays for large s as a power law, C(s) ~ s^(-gamma). For continental stations, including stations along the coastlines, we find that gamma is always close to 0.7. For stations on islands, we find that gamma ranges between 0.3 and 0.7, with a maximum at gamma = 0.4. This is consistent with earlier studies of the persistence in sea surface temperature records where gamma is close to 0.4. In all cases, the exponent gamma does not depend on the distance of the stations to the continental coastlines. By varying the degree of detrending in the fluctuation analysis we obtain also information about trends in the temperature records.Comment: 5 pages, 4 including eps figure

Towards Translational ImmunoPET/MR Imaging of Invasive Pulmonary Aspergillosis: The Humanised Monoclonal Antibody JF5 Detects Aspergillus Lung Infections In Vivo

This is the final published versionAvailable from Ivyspring International Publisher via the DOI in this recordInvasive pulmonary aspergillosis (IPA) is a life-threatening lung disease of hematological malignancy and bone marrow transplant patients caused by the ubiquitous environmental fungus Aspergillus fumigatus. Current diagnostic tests for the disease lack sensitivity as well as specificity, and culture of the fungus from invasive lung biopsy, considered the gold standard for IPA detection, is slow and often not possible in critically ill patients. In a previous study, we reported the development of a novel non-invasive procedure for IPA diagnosis based on antibody-guided positron emission tomography and magnetic resonance imaging (immunoPET/MRI) using a [64Cu]DOTA-labeled mouse monoclonal antibody (mAb), mJF5, specific to Aspergillus. To enable translation of the tracer to the clinical setting, we report here the development of a humanised version of the antibody (hJF5), and pre-clinical imaging of lung infection using a [64Cu]NODAGA-hJF5 tracer. The humanised antibody tracer shows a significant increase in in vivo biodistribution in A. fumigatus infected lungs compared to its radiolabeled murine counterpart [64Cu]NODAGA-mJF5. Using reverse genetics of the pathogen, we show that the antibody binds to the antigenic determinant 1,5-galactofuranose (Galf) present in a diagnostic mannoprotein antigen released by the pathogen during invasive growth in the lung. The absence of the epitope Galf in mammalian carbohydrates, coupled with the enhanced imaging capabilities of the hJF5 antibody, means that the [64Cu]NODAGA-hJF5 tracer developed here represents an ideal candidate for the diagnosis of IPA and translation to the clinical setting.This work was supported by the European Union Seventh Framework Programme FP7/2007-2013 under Grant 602820, the Deutsche Forschungsgemeinschaft (Grant WI3777/1-2 to SW), and the Werner Siemens Foundation. We thank Sven Krappman for use of the A. fumigatustdTomato strain, and acknowledge the Imaging Centre Essen (IMCES) for assistance with optical imaging of lungs

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

Soft X-Ray Projection Lithography Using a 1-1 Ring Field Optical-System

An iridium-coated Offner 1:1 ring field camera has been used to carry out projection lithography using 42 nm light from an undulator in the vacuum ultra violet storage ring at Brookhaven National Laboratory. Near-diffraction-limited resolution has been obtained showing features as small as 0.2-mu-m within a 2 mm x 0.25 mm image field. Images of both transmission and reflection masks have been obtained. The impact of source coherence on imagery has been investigated. Hydrocarbon contamination problems experienced in this photon energy range have been investigated and possible solutions are suggested

Architecture of Pol II(G) and molecular mechanism of transcription regulation by Gdown1.

Tight binding of Gdown1 represses RNA polymerase II (Pol II) function in a manner that is reversed by Mediator, but the structural basis of these processes is unclear. Although Gdown1 is intrinsically disordered, its Pol II interacting domains were localized and shown to occlude transcription factor IIF (TFIIF) and transcription factor IIB (TFIIB) binding by perfect positioning on their Pol II interaction sites. Robust binding of Gdown1 to Pol II is established by cooperative interactions of a strong Pol II binding region and two weaker binding modulatory regions, thus providing a mechanism both for tight Pol II binding and transcription inhibition and for its reversal. In support of a physiological function for Gdown1 in transcription repression, Gdown1 co-localizes with Pol II in transcriptionally silent nuclei of early Drosophila embryos but re-localizes to the cytoplasm during zygotic genome activation. Our study reveals a self-inactivation through Gdown1 binding as a unique mode of repression in Pol II function