AMPK Directly Inhibits NDPK Through a Phosphoserine Switch to Maintain Cellular Homeostasis

AMP-activated protein kinase (AMPK) is a key energy sensor that regulates metabolism to maintain cellular energy balance. AMPK activation has also been proposed to mimic benefits of caloric restriction and exercise. Therefore, identifying downstream AMPK targets could elucidate new mechanisms for maintaining cellular energy homeostasis. We identified the phosphotransferase nucleoside diphosphate kinase (NDPK), which maintains pools of nucleotides, as a direct AMPK target through the use of two-dimensional differential in-gel electrophoresis. Furthermore, we mapped the AMPK/NDPK phosphorylation site (serine 120) as a functionally potent enzymatic “off switch” both in vivo and in vitro. Because ATP is usually the most abundant cellular nucleotide, NDPK would normally consume ATP, whereas AMPK would inhibit NDPK to conserve energy. It is intriguing that serine 120 is mutated in advanced neuroblastoma, which suggests a mechanism by which NDPK in neuroblastoma can no longer be inhibited by AMPK-mediated phosphorylation. This novel placement of AMPK upstream and directly regulating NDPK activity has widespread implications for cellular energy/nucleotide balance, and we demonstrate in vivo that increased NDPK activity leads to susceptibility to energy deprivation–induced death

A diamond AGPM coronagraph for VISIR

In recent years, phase mask coronagraphy has become increasingly efficient in imaging the close environment of stars, enabling the search for exoplanets and circumstellar disks. Coronagraphs are ideally suited instruments, characterized by high dynamic range imaging capabilities, while preserving a small inner working angle. The AGPM (Annular Groove Phase Mask, Mawet et al. 2005) consists of a vector vortex induced by a rotationally symmetric subwavelength grating. This technique constitutes an almost unique solution to the achromatization at longer wavelengths (mid-infrared). For this reason, we have specially conceived a mid-infrared AGPM coronagraph for the forthcoming upgrade of VISIR, the mid-IR imager and spectrograph on the VLT at ESO (Paranal), in collaboration with members of the VISIR consortium. The implementation phase of the VISIR Upgrade Project is foreseen for May-August 2012, and the AGPM installed will cover the 11-13.2 μm spectral range. In this paper, we present the entire fabrication process of our AGPM imprinted on a diamond substrate. Diamond is an ideal material for mid-infrared wavelengths owing to its high transparency, small dispersion, extremely low thermal expansion and outstanding mechanical and chemical properties. The design process has been performed with an algorithm based on the rigorous coupled wave analysis (RCWA), and the micro-fabrication has been carried out using nano-imprint lithography and reactive ion etching. A precise grating profile metrology has also been conducted using cleaving techniques. Finally, we show the deposit of fiducials (i.e. centering marks) with Aerosol Jet Printing (AJP). We conclude with the ultimate coronagraph expected performances

L'-band AGPM vector vortex coronagraph's first light on LBTI/LMIRCam

We present the first observations obtained with the L'-band AGPM vortex coronagraph recently installed on LBTI/LMIRCam. The AGPM (Annular Groove Phase Mask) is a vector vortex coronagraph made from diamond subwavelength gratings. It is designed to improve the sensitivity and dynamic range of high-resolution imaging at very small inner working angles, down to 0.09 arcseconds in the case of LBTI/LMIRCam in the L' band. During the first hours on sky, we observed the young A5V star HR\,8799 with the goal to demonstrate the AGPM performance and assess its relevance for the ongoing LBTI planet survey (LEECH). Preliminary analyses of the data reveal the four known planets clearly at high SNR and provide unprecedented sensitivity limits in the inner planetary system (down to the diffraction limit of 0.09 arcseconds).Comment: 9 pages, 4 figures, SPIE proceeding

Density growth in Kantowski-Sachs cosmologies with cosmological constant

In this work the growth of density perturbations in Kantowski-Sachs cosmologies with a positive cosmological constant is studied, using the 1+3 and 1+1+2 covariant formalisms. For each wave number we obtain a closed system for scalars formed from quantities that are zero on the background and hence are gauge-invariant. The solutions to this system are then analyzed both analytically and numerically. In particular the effects of anisotropy and the behaviour close to a bounce in the cosmic scale factor are considered. We find that typically the density gradient in the bouncing directions experiences a local maximum at or slightly after the bounce.Comment: 33 pages, 17 picture

Testing in the incremental design and development of complex products

Testing is an important aspect of design and development which consumes significant time and resource in many companies. However, it has received less research attention than many other activities in product development, and especially, very few publications report empirical studies of engineering testing. Such studies are needed to establish the importance of testing and inform the development of pragmatic support methods. This paper combines insights from literature study with findings from three empirical studies of testing. The case studies concern incrementally developed complex products in the automotive domain. A description of testing practice as observed in these studies is provided, confirming that testing activities are used for multiple purposes depending on the context, and are intertwined with design from start to finish of the development process, not done after it as many models depict. Descriptive process models are developed to indicate some of the key insights, and opportunities for further research are suggested

Decay of the High-K Isomeric State to a Rotational Band in 257Rf

The 257Rf isotope has been populated via the 208Pb(50Ti, n) fusion-evaporation reaction and delayed gamma-ray and electron decay spectroscopy has been performed. The existence of a high-K isomeric state in 257Rf has been confirmed. The isomeric state decays into a rotational band based on the 11/2(-)[725] excitation, which was observed up to spin of (23/2(-)). Three multipolarity-E1 gamma transitions depopulating the isomeric state have been observed, which fixes the spin for that state to (21/2(+)). This assignment agrees with theoretical predictions calculated with the microscopic-macroscopic approach, which suggest the isomeric state to be formed by coupling an unpaired 11/2(-)[725] quasineutron to the (1/2(-)[521] circle times 9/2(+)[624])(5)- two-quasiproton state. The same two-quasiproton excitation is possible for the lowest isomer in 256Rf

The AGES-Reykjavik study atlases: Non-linear multi-spectral template and atlases for studies of the ageing brain

Neuro Imaging Researc

Probing the Hofmeister Effect with Ultrafast Core Hole Spectroscopy

In the current work, X-ray emission spectra of aqueous solutions of different inorganic salts within the Hofmeister series are presented. The results reflect the direct interaction of the ions with the water molecules and therefore, reveal general properties of the salt-water interactions. Within the experimental precision a significant effect of the ions on the water structure has been observed but no ordering according to the structure maker/structure breaker concept could be mirrored in the results indicating that the Hofmeister effect-if existent-may be caused by more complex interactions