Quasi full-disk maps of solar horizontal velocities using SDO/HMI data

For the first time, the motion of granules (solar plasma on the surface on scales larger than 2.5 Mm) has been followed over the entire visible surface of the Sun, using SDO/HMI white-light data. Horizontal velocity fields are derived from image correlation tracking using a new version of the coherent structure tracking algorithm.The spatial and temporal resolutions of the horizontal velocity map are 2.5 Mm and 30 min respectively . From this reconstruction, using the multi-resolution analysis, one can obtain to the velocity field at different scales with its derivatives such as the horizontal divergence or the vertical component of the vorticity. The intrinsic error on the velocity is ~0.25 km/s for a time sequence of 30 minutes and a mesh size of 2.5 Mm.This is acceptable compared to the granule velocities, which range between 0.3 km/s and 1.8 km/s. A high correlation between velocities computed from Hinode and SDO/HMI has been found (85%). From the data we derive the power spectrum of the supergranulation horizontal velocity field, the solar differential rotation, and the meridional velocity.Comment: 8 pages, 11 figures, accepted in Astronomy and Astrophysic

Experimental approach to evaluate the influence of characteristic length on the dynamics of biphasic flow in vacuum impregnation.

Vacuum impregnation (VI) is a process of fluid replacement in porous media by reduction in atmospheric pressure and its subsequent reestablishment. The objective of this study was to evaluate the influence of the characteristic length and viscosity of impregnating fluids on vacuum impregnation dynamics. Refractory ceramic samples were used as a non-deformable porous media model, and a device continuously recorded the changes in net force (difference between weight force and buoyant force) on the sample through a load cell during the impregnation process. The relative values for the sample’s volumetric fraction due to spontaneous imbibition, for the drained fraction due to vacuum application, and for impregnation due to pressure reestablishment were estimated. The total volumetric fraction estimated during VI by the experimental device was compared with the values estimated by a balance and with those predicted by an equilibrium model. The experimental device was shown to be useful to determine impregnation kinetics, it was accurate and obtained values very close to the ones estimated by the balance and predicted by theoretical models. As expected, the kinetics was dependent on fluid viscosity and on the sample’s characteristic length. The kinetics data allowed the minimum time step at the VI process to be determined, enabling the optimization of the process applied to large media or in viscous fluid impregnation

Heat exchanger/reactors (HEX reactors): Concepts, technologies: State-of-the-art

Process intensification is a chemical engineering field which has truly emerged in the past few years and is currently rapidly growing. It consists in looking for safer operating conditions, lower waste in terms of costs and energy and higher productivity; and away to reach such objectives is to develop multifunctional devices such as heat exchanger/reactors for instance. This review is focused on the latter and makes a point on heat exchanger/reactors. After a brief presentation of requirements due to transposition from batch to continuous apparatuses, heat exchangers/reactors at industrial or pilot scales and their applications are described

Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®.

Multi-gene prognostic signatures including the Oncotype® DX Recurrence Score (RS), EndoPredict® (EP) and Prosigna® (Risk Of Recurrence, ROR) are widely used to predict the likelihood of distant recurrence in patients with oestrogen-receptor-positive (ER+), HER2-negative breast cancer. Here, we describe the development and validation of methods to recapitulate RS, EP and ROR scores from NanoString expression data. RNA was available from 107 tumours from postmenopausal women with early-stage, ER+, HER2- breast cancer from the translational Arimidex, Tamoxifen, Alone or in Combination study (TransATAC) where previously these signatures had been assessed with commercial methodology. Gene expression was measured using NanoString nCounter. For RS and EP, conversion factors to adjust for cross-platform variation were estimated using linear regression. For ROR, the steps to perform subgroup-specific normalisation of the gene expression data and calibration factors to calculate the 46-gene ROR score were assessed and verified. Training with bootstrapping (n = 59) was followed by validation (n = 48) using adjusted, research use only (RUO) NanoString-based algorithms. In the validation set, there was excellent concordance between the RUO scores and their commercial counterparts (rc(RS) = 0.96, 95% CI 0.93-0.97 with level of agreement (LoA) of -7.69 to 8.12; rc(EP) = 0.97, 95% CI 0.96-0.98 with LoA of -0.64 to 1.26 and rc(ROR) = 0.97 (95% CI 0.94-0.98) with LoA of -8.65 to 10.54). There was also a strong agreement in risk stratification: (RS: κ = 0.86, p < 0.0001; EP: κ = 0.87, p < 0.0001; ROR: κ = 0.92, p < 0.001). In conclusion, the calibrated algorithms recapitulate the commercial RS and EP scores on individual biopsies and ROR scores on samples based on subgroup-centreing method using NanoString expression data

IL-37 exerts therapeutic effects in experimental autoimmune encephalomyelitis through the receptor complex IL-1R5/IL-1R8

Background: Interleukin 37 (IL-37), a member of IL-1 family, broadly suppresses inflammation in many pathological conditions by acting as a dual-function cytokine in that IL-37 signals via the extracellular receptor complex IL1-R5/IL-1R8, but it can also translocate to the nucleus. However, whether IL-37 exerts beneficial actions in neuroinflammatory diseases, such as multiple sclerosis, remains to be elucidated. Thus, the goals of the present study were to evaluate the therapeutic effects of IL-37 in a mouse model of multiple sclerosis, and if so, whether this is mediated via the extracellular receptor complex IL-1R5/IL-1R8. Methods: We used a murine model of MS, the experimental autoimmune encephalomyelitis (EAE). We induced EAE in three different single and double transgenic mice (hIL-37tg, IL-1R8 KO, hIL-37tg-IL-1R8 KO) and wild type littermates. We also induced EAE in C57Bl/6 mice and treated them with various forms of recombinant human IL-37 protein. Functional and histological techniques were used to assess locomotor deficits and demyelination. Luminex and flow cytometry analysis were done to assess the protein levels of pro-inflammatory cytokines and different immune cell populations, respectively. qPCRs were done to assess the expression of IL-37, IL-1R5 and IL-1R8 in the spinal cord of EAE, and in blood peripheral mononuclear cells and brain tissue samples of MS patients. Results: We demonstrate that IL-37 reduces inflammation and protects against neurological deficits and myelin loss in EAE mice by acting via IL1-R5/IL1-R8. We also reveal that administration of recombinant human IL-37 exerts therapeutic actions in EAE mice. We finally show that IL-37 transcripts are not up-regulated in peripheral blood mononuclear cells and in brain lesions of MS patients, despite the IL-1R5/IL-1R8 receptor complex is expressed. Conclusions: This study presents novel data indicating that IL-37 exerts therapeutic effects in EAE by acting through the extracellular receptor complex IL-1R5/IL-1R8, and that this protective physiological mechanism is defective in MS individuals. IL-37 may therefore represent a novel therapeutic avenue for the treatment of MS with great promising potential

Strigolactones inhibit auxin feedback on PIN-dependent auxin transport canalization

Directional transport of the phytohormone auxin is a versatile, plant-specific mechanism regulating many aspects of plant development. The recently identified plant hormones, strigolactones (SLs), are implicated in many plant traits; among others, they modify the phenotypic output of PIN-FORMED (PIN) auxin transporters for fine-tuning of growth and developmental responses. Here, we show in pea and Arabidopsis that SLs target processes dependent on the canalization of auxin flow, which involves auxin feedback on PIN subcellular distribution. D14 receptor- and MAX2 F-box-mediated SL signaling inhibits the formation of auxin-conducting channels after wounding or from artificial auxin sources, during vasculature de novo formation and regeneration. At the cellular level, SLs interfere with auxin effects on PIN polar targeting, constitutive PIN trafficking as well as clathrin-mediated endocytosis. Our results identify a non-transcriptional mechanism of SL action, uncoupling auxin feedback on PIN polarity and trafficking, thereby regulating vascular tissue formation and regeneration

Mutational analysis of the latency-associated nuclear antigen DNA-binding domain of Kaposi's sarcoma-associated herpesvirus reveals structural conservation among gammaherpesvirus origin-binding proteins

The latency-associated nuclear antigen (LANA) of Kaposi's sarcoma-associated herpesvirus functions as an origin-binding protein (OBP) and transcriptional regulator. LANA binds the terminal repeats via the C-terminal DNA-binding domain (DBD) to support latent DNA replication. To date, the structure of LANA has not been solved. Sequence alignments among OBPs of gammaherpesviruses have revealed that the C terminus of LANA is structurally related to EBNA1, the OBP of Epstein–Barr virus. Based on secondary structure predictions for LANADBD and published structures of EBNA1DBD, this study used bioinformatics tools to model a putative structure for LANADBD bound to DNA. To validate the predicted model, 38 mutants targeting the most conserved motifs, namely three α-helices and a conserved proline loop, were constructed and functionally tested. In agreement with data for EBNA1, residues in helices 1 and 2 mainly contributed to sequence-specific DNA binding and replication activity, whilst mutations in helix 3 affected replication activity and multimer formation. Additionally, several mutants were isolated with discordant phenotypes, which may aid further studies into LANA function. In summary, these data suggest that the secondary and tertiary structures of LANA and EBNA1 DBDs are conserved and are critical for (i) sequence-specific DNA binding, (ii) multimer formation, (iii) LANA-dependent transcriptional repression, and (iv) DNA replication

Isolated terawatt attosecond hard X-ray pulse generated from single current spike

Isolated terawatt (TW) attosecond (as) hard X-ray pulse is greatly desired for four-dimensional investigations of natural phenomena with picometer spatial and attosecond temporal resolutions. Since the demand for such sources is continuously increasing, the possibility of generating such pulse by a single current spike without the use of optical or electron delay units in an undulator line is addressed. The conditions of a current spike (width and height) and a modulation laser pulse (wavelength and power) is also discussed. We demonstrate that an isolated TW-level as a hard X-ray can be produced by a properly chosen single current spike in an electron bunch with simulation results. By using realistic specifications of an electron bunch of the Pohang Accelerator Laboratory X-ray Free-Electron Laser (PAL-XFEL), we show that an isolated, &gt;1.0 TW and similar to 36 as X-ray pulse at 12.4 keV can be generated in an optimized-tapered undulator line. This result opens a new vista for current XFEL operation: the attosecond XFEL

Measurements of Compression and Emittance Growth after the First LCLS Bunch Compressor Chicane

The Linac Coherent Light Source (LCLS) is a SASE xray free-electron laser project presently under construction at SLAC. The injector section from RF photocathode gun through first bunch compressor chicane was installed during the fall of 2006. The first bunch compressor is located at 250 MeV and nominally compresses a 1-nC electron bunch from an rms length of about 1 mm to 0.2 mm. Transverse phase space and bunch length diagnostics are located immediately after the chicane. We present preliminary measurements and simulations of the longitudinal and transverse phase space after the chicane in various beam conditions, including extreme compression with micron-scale current spikes

Sphingolipid Modulation Activates Proteostasis Programs to Govern Human Hematopoietic Stem Cell Self-Renewal.

Cellular stress responses serve as crucial decision points balancing persistence or culling of hematopoietic stem cells (HSCs) for lifelong blood production. Although strong stressors cull HSCs, the linkage between stress programs and self-renewal properties that underlie human HSC maintenance remains unknown, particularly at quiescence exit when HSCs must also dynamically shift metabolic state. Here, we demonstrate distinct wiring of the sphingolipidome across the human hematopoietic hierarchy and find that genetic or pharmacologic modulation of the sphingolipid enzyme DEGS1 regulates lineage differentiation. Inhibition of DEGS1 in hematopoietic stem and progenitor cells during the transition from quiescence to cellular activation with N-(4-hydroxyphenyl) retinamide activates coordinated stress pathways that coalesce on endoplasmic reticulum stress and autophagy programs to maintain immunophenotypic and functional HSCs. Thus, our work identifies a linkage between sphingolipid metabolism, proteostatic quality control systems, and HSC self-renewal and provides therapeutic targets for improving HSC-based cellular therapeutics.E.L. is supported by Wellcome grant 107630/Z/15/Z and a core support grant from the Wellcome and MRC to the Wellcome-Medical Research Council Cambridge Stem Cell Institute. C.L. is supported by U.S. NIH, NCI Grant P01-CA097132. JED is supported by funds from the Princess Margaret Cancer Centre Foundation, Canadian Institutes for Health Research, Joint Canada-Israel Health Research Program, Terry Fox Foundation, and a Canada Research Chair