The Atomic and Electronic Structure of Liquid N- Methylformamide as Determined from Diffraction Experiments

The structure of liquid N-methylformamide (NMF) has been investigated using synchrotron radiation at 77 and 95 keV. The use of high energy photons has several advantages, in this case especially the large accessible momentum transfer range, the low absorption and the direct comparability with neutron diffraction. The range of momentum transfer covered is 0.6 \AA$^{-1} <$ Q $<$24.0 \AA$^{-1}$. Neutron diffraction data on the same sample in the same momentum transfer range have been published previously. In that study two differently isotope - substituted species were investigated. In order to compare neutron and photon diffraction data properly Reverse Monte Carlo (RMC-) simulations have been performed. Some modifications had to be added to the standard RMC- code introducing different constraints for inter- and intramolecular distances as these distances partly overlap in liquid NMF. RMC- simulations having only the neutron data as input were carried out in order to test the quality of the X-ray data. The photon structure factor calculated from the RMC- configurations is found to agree well with the present experimental data, while it deviates considerably from earlier X-ray work using low energy photons (17 keV). Finally we discuss whether the different interaction mechanisms of neutrons and photons can be used to directly access the electronic structure in the liquid. Evidence is presented that the elastic self scattering part of liquid NMF is changed with respect to the independent atom approximation. This modification can be accounted for by a simple charged atoms model.Comment: Accepted for publication in Molecular Physics, LaTex file, 12 pages, figures not include

Ankyrin repeat and Single KH domain 1 (ANKHD1) drives renal cancer cell proliferation via binding to and altering a subset of miRNAs

Clear cell Renal Cell Carcinoma (ccRCC) represents the most common kidney cancer worldwide. Increased cell proliferation associated with abnormal microRNA (miRNA) regulation are hallmarks of carcinogenesis. Ankyrin repeat and single KH domain 1 (ANKHD1) is a highly conserved protein found to interact with core cancer pathways in Drosophila, however its involvement in RCC is completely unexplored. Quantitative PCR studies coupled with large-scale genomics data analyses demonstrated that ANKHD1 is significantly upregulated in kidneys of RCC patients when compared to healthy controls. Cell cycle analyses revealed that ANKHD1 is an essential factor for RCC cell division. To understand the molecular mechanism(s) utilized by ANKHD1 to drive RCC cell proliferation we performed bioinformatics analyses which revealed that ANKHD1 contains a putative miRNA-binding motif. We screened 48 miRNAs with tumour-enhancing or suppressing activities, and found that ANKHD1 binds to and regulates three tumour-suppressing miRNAs (i.e. miR-29a, miR-205, and miR-196a). RNA-immunoprecipitation assays demonstrated that ANKHD1 physically interacts with its target miRNAs via a single K-Homology (KH)-domain, located in the c-terminus of the protein. Functionally we discovered that ANKHD1 positively drives ccRCC cell mitosis via binding to and suppressing mainly miR-29a and to a lesser degree via miR-196a/205, leading to an upregulation in pro-proliferative genes such as CCDN1. Collectively, these data identify ANKHD1 as a new regulator of ccRCC proliferation via specific miRNA interactions

Matters of the heart

What does it take to make a heart? Even in the fruit fly, in which matters of the heart don’t extend to either pop music or pulp fiction, making a heart requires big decisions and processes of surprising complexity

Ken&Barbie selectively regulates the expression of a subset of JAK/STAT pathway target genes.

SummaryA limited number of evolutionarily conserved signal transduction pathways are repeatedly reused during development to regulate a wide range of processes. Here we describe a new negative regulator of JAK/STAT signaling and identify a potential mechanism by which the pleiotropy of responses resulting from pathway activation is generated in vivo. As part of a genetic interaction screen, we have identified Ken & Barbie (Ken) [1], which is an ortholog of the mammalian proto-oncogene BCL6 [2], as a negative regulator of the JAK/STAT pathway. Ken genetically interacts with the pathway in vivo and recognizes a DNA consensus sequence overlapping that of STAT92E in vitro. Tissue culture-based assays demonstrate the existence of Ken-sensitive and Ken-insensitive STAT92E binding sites, while ectopically expressed Ken is sufficient to downregulate a subset of JAK/STAT pathway target genes in vivo. Finally, we show that endogenous Ken specifically represses JAK/STAT-dependent expression of ventral veins lacking (vvl) in the posterior spiracles. Ken therefore represents a novel regulator of JAK/STAT signaling whose dynamic spatial and temporal expression is capable of selectively modulating the transcriptional repertoire elicited by activated STAT92E in vivo

Modulation of human JAK-STAT pathway signaling by functionally conserved regulators

Both the core JAK-STAT pathway components and their in vivo roles have been widely conserved between vertebrates and invertebrate models such as Drosophila melanogaster. Misregulation of JAK-STAT pathway activity has also been identified as a key factor in the development of multiple human malignancies. Recently, whole genome RNA interference (RNAi) screens in cultured Drosophila cells have identified both positively and negatively acting JAK-STAT pathway regulators. Here, we describe the analysis of 73 human genes representing homologs of 56 Drosophila genes originally identified by genome-wide RNAi screening as regulators of JAK-STAT signaling. Using assays for human STAT1 and STAT3 protein levels and phosphorylation status, as well as assays measuring the expression of endogenous STAT1 and STAT3 transcriptional targets, we have tested siRNAs targeting these 73 human genes and have identified potential JAK-STAT pathway regulatory roles in 69 (95%) of these. The genes identified represent a wide range of human JAK-STAT pathway regulators and include genes not previously known to modulate this signaling cascade. These results underline the value of model system based approaches for the identification of pathway regulators and have led to the identification of loci whose misregulation may ultimately be implicated in JAK-STAT pathway-mediated human disease

Physical Properties of OSIRIS-REx Target Asteroid (101955) 1999 RQ36 derived from Herschel, ESO-VISIR and Spitzer observations

In September 2011, the Herschel Space Observatory performed an observation campaign with the PACS photometer observing the asteroid (101955) 1999 RQ36 in the far infrared. The Herschel observations were analysed, together with ESO VLT-VISIR and Spitzer-IRS data, by means of a thermophysical model in order to derive the physical properties of 1999 RQ36. We find the asteroid has an effective diameter in the range 480 to 511 m, a slightly elongated shape with a semi-major axis ratio of a/b=1.04, a geometric albedo of 0.045 +0.015/-0.012, and a retrograde rotation with a spin vector between -70 and -90 deg ecliptic latitude. The thermal emission at wavelengths below 12 micron -originating in the hot sub-solar region- shows that there may be large variations in roughness on the surface along the equatorial zone of 1999 RQ36, but further measurements are required for final proof. We determine that the asteroid has a disk-averaged thermal inertia of Gamma = 650 Jm-2s-0.5K-1 with a 3-sigma confidence range of 350 to 950 Jm-2s-0.5K-1, equivalent to what is observed for 25143 Itokawa and suggestive that 1999 RQ36 has a similar surface texture and may also be a rubble-pile in nature. The low albedo indicates that 1999 RQ36 very likely contains primitive volatile-rich material, consistent with its spectral type, and that it is an ideal target for the OSIRIS-REx sample return mission.Comment: Accepted for publication in Astronomy & Astrophysics, 9 pages, 7 figure

Numerical Bifurcation Analysis of Conformal Formulations of the Einstein Constraints

The Einstein constraint equations have been the subject of study for more than fifty years. The introduction of the conformal method in the 1970's as a parameterization of initial data for the Einstein equations led to increased interest in the development of a complete solution theory for the constraints, with the theory for constant mean curvature (CMC) spatial slices and closed manifolds completely developed by 1995. The first general non-CMC existence result was establish by Holst et al. in 2008, with extensions to rough data by Holst et al. in 2009, and to vacuum spacetimes by Maxwell in 2009. The non-CMC theory remains mostly open; moreover, recent work of Maxwell on specific symmetry models sheds light on fundamental non-uniqueness problems with the conformal method as a parameterization in non-CMC settings. In parallel with these mathematical developments, computational physicists have uncovered surprising behavior in numerical solutions to the extended conformal thin sandwich formulation of the Einstein constraints. In particular, numerical evidence suggests the existence of multiple solutions with a quadratic fold, and a recent analysis of a simplified model supports this conclusion. In this article, we examine this apparent bifurcation phenomena in a methodical way, using modern techniques in bifurcation theory and in numerical homotopy methods. We first review the evidence for the presence of bifurcation in the Hamiltonian constraint in the time-symmetric case. We give a brief introduction to the mathematical framework for analyzing bifurcation phenomena, and then develop the main ideas behind the construction of numerical homotopy, or path-following, methods in the analysis of bifurcation phenomena. We then apply the continuation software package AUTO to this problem, and verify the presence of the fold with homotopy-based numerical methods.Comment: 13 pages, 4 figures. Final revision for publication, added material on physical implication

Application des techniques de contrôle des écoulements au pilotage des projectiles : Contrôle fluidique d'un projectile gyrostabilisé de 155 mm par effet Coanda

In order to increase weapons performances, manufacturers consider to produce projectiles incorporating a trajectory correction capability. The main goal is also to reduce the projectile scattering error. For aero-stabilized munitions, the control of the projectile path is carried out via airfoil surfaces, technologies mastered for decades. However, the control of a spin- stabilized projectiles is much more complex. Indeed, the flight conditions of a 155 mm spin-stabilized projectile range from high subsonic to supersonic velocities so the control device has to be adapted to all flight regimes. Moreover, the projectile has to spin to insure its stability during the flight. Then, the control devices have to be actuated at the projectile spin rate to create a significant deviation. These devices need to be low-cost and easily installed in the projectile too. This work also focuses on a promising fluidic control adapted to the previous constraints : the Coanda effect. RANS and URANS computations are performed to evaluate the aerodynamic forces generated by the Coanda effect for respectively a spinning and a non-spinning projectile. Then, 6-dof flight mechanics simulations are realized to assess the downrange and crossrange deviation of the controlled projectile. Finally, a large-eddy simulation of a simplified geometry has been conducted in order to improve our understanding of the physical mechanisms induced by the control device.Afin d'améliorer les performances des systèmes d'armes, les industriels de l'armement envisagent la mise en service de projectiles intégrant une capacité de correction de trajectoires. Le principal objectif consiste à proposer de nouveaux dispositifs de correction permettant de réduire l'erreur de dispersion de l'engin. Dans le cadre de projectiles aérostabilisés, le contrôle de leurs trajectoires est assuré à l'aide de surfaces portantes, technologie éprouvée depuis de nombreuses décennies. Néanmoins, le contrôle de la trajectoire d'un projectile gyrostabilisé s'avère plus délicat. En effet, les conditions extérieures de ce dernier varient du régime haut subsonique au régime supersonique. Le dispositif de contrôle doit par conséquent être adapté à tous les régimes de vol. De plus, une vitesse de rotation est inculquée au projectile afin de le stabiliser au cours de son vol. Cette rotation représente une énorme contrainte puisque le dispositif doit agir dans une direction azimutale donnée afin de générer une déviation significative. Il doit en plus être facilement implémentable et conserver un coût raisonnable. Ces travaux se proposent par conséquent d'évaluer un dispositif de contrôle prometteur et adapté aux contraintes décrites précédemment : l'effet Coanda. Des simulations RANS et URANS ont été initialement réalisées afin d'évaluer les efforts aérodynamiques générés par cet effet. Des simulations de mécanique du vol ont ensuite été conduites afin de déterminer les déviations engendrables par ce dispositif. Une simulation des grandes échelles d'une configuration simplifiée contrôlée par effet Coanda est finalement proposée afin d'améliorer notre compréhension des mécanismes physiques induits par l'utilisation d'un tel dispositif