Nuclear Dbf2-related protein kinases (NDRs) in isolated cardiac myocytes and the myocardium: activation by cellular stresses and by phosphoprotein serine-/threonine-phosphatase inhibitors

The nuclear Dbf2-related protein kinases 1 and 2 (NDR1/2) are closely-related AGC family kinases that are strongly conserved through evolution. In mammals, they are activated inter alia by phosphorylation of an hydrophobic domain threonine-residue [NDR1(Thr-444)/NDR2(Thr-442)] by an extrinsic protein kinase followed by autophosphorylation of a catalytic domain serine-residue [NDR1(Ser-281)/NDR2(Ser-282)]. We examined NDR1/2 expression and regulation in primary cultures of neonatal rat cardiac myocytes and in perfused adult rat hearts. In myocytes, transcripts for NDR2, but not NDR1, were induced by the hypertrophic agonist, endothelin-1. NDR1(Thr-444) and NDR2(Thr-442) were rapidly phosphorylated (maximal in 15-30 min) in myocytes exposed to some phosphoprotein Ser-/Thr-phosphatase 1/2 inhibitors (calyculin A, okadaic acid) and, to a lesser extent, by hyperosmotic shock, low concentrations of H(2)O(2), or chelerythrine. In myocytes adenovirally-transduced to express FLAG-NDR2 (which exhibited a mainly-cytoplasmic localisation), the same agents increased FLAG-NDR2 activity as assessed by in vitro protein kinase assays, indicative of FLAG-NDR2(Ser-282/Thr-442) phosphorylation. Calyculin A-induced phosphorylation of NDR1(Thr-444)/NDR2(Thr-442) and activation of FLAG-NDR2 were inhibited by staurosporine, but not by other protein kinase inhibitors tested. In ex vivo rat hearts, NDR1(Thr-444)/NDR2(Thr-442) were phosphorylated in response to ischaemia-reperfusion or calyculin A. From a pathological viewpoint, we conclude that activities of NDR1 and NDR2 are responsive to cytotoxic stresses in heart preparations and this may represent a previously-unidentified response to myocardial ischaemia in vivo

Very high energy gamma rays from the direction of Sagittarius A*.

We report the detection of a point-like source of very high energy (VHE) -rays coincident within 1' of Sgr A *, obtained with the HESS array of Cherenkov telescopes. The -rays exhibit a power-law energy spectrum with a spectral index of and a flux above the 165 GeV threshold of m -2 s -1. The measured flux and spectrum differ substantially from recent results reported in particular by the CANGAROO collaboration

Discovery of VHE gamma-rays from the high-frequency-peaked BL Lac object RGB J0152+017

Aims: The BL Lac object RGB J0152+017 (z=0.080) was predicted to be a very high-energy (VHE; > 100 GeV) gamma-ray source, due to its high X-ray and radio fluxes. Our aim is to understand the radiative processes by investigating the observed emission and its production mechanism using the High Energy Stereoscopic System (H.E.S.S.) experiment. Methods: We report recent observations of the BL Lac source RGB J0152+017 made in late October and November 2007 with the H.E.S.S. array consisting of four imaging atmospheric Cherenkov telescopes. Contemporaneous observations were made in X-rays by the Swift and RXTE satellites, in the optical band with the ATOM telescope, and in the radio band with the Nancay Radio Telescope. Results: A signal of 173 gamma-ray photons corresponding to a statistical significance of 6.6 sigma was found in the data. The energy spectrum of the source can be described by a powerlaw with a spectral index of 2.95+/-0.36stat+/-0.20syst. The integral flux above 300 GeV corresponds to ~2% of the flux of the Crab nebula. The source spectral energy distribution (SED) can be described using a two-component non-thermal synchrotron self-Compton (SSC) leptonic model, except in the optical band, which is dominated by a thermal host galaxy component. The parameters that are found are very close to those found in similar SSC studies in TeV blazars. Conclusions: RGB J0152+017 is discovered as a source of VHE gamma-rays by H.E.S.S. The location of its synchrotron peak, as derived from the SED in Swift data, allows clearly classification it as a high-frequency-peaked BL Lac (HBL).Comment: Accepted for publication in A&A Letters (5 pages, 4 figures

A possible association of the new VHE gamma-ray source HESS J1825--137 with the pulsar wind nebula G18.0--0.7

We report on a possible association of the recently discovered very high-energy $\gamma$-ray source HESS J1825--137 with the pulsar wind nebula (commonly referred to as G 18.0--0.7) of the $2.1\times 10^{4}$ year old Vela-like pulsar PSR B1823--13. HESS J1825--137 was detected with a significance of 8.1 $\sigma$ in the Galactic Plane survey conducted with the H.E.S.S. instrument in 2004. The centroid position of HESS J1825--137 is offset by 11\arcmin south of the pulsar position. \emph{XMM-Newton} observations have revealed X-ray synchrotron emission of an asymmetric pulsar wind nebula extending to the south of the pulsar. We argue that the observed morphology and TeV spectral index suggest that HESS J1825--137 and G 18.0--0.7 may be associated: the lifetime of TeV emitting electrons is expected to be longer compared to the {\it XMM-Newton} X-ray emitting electrons, resulting in electrons from earlier epochs (when the spin-down power was larger) contributing to the present TeV flux. These electrons are expected to be synchrotron cooled, which explains the observed photon index of $\sim 2.4$, and the longer lifetime of TeV emitting electrons naturally explains why the TeV nebula is larger than the X-ray size. Finally, supernova remnant expansion into an inhomogeneous medium is expected to create reverse shocks interacting at different times with the pulsar wind nebula, resulting in the offset X-ray and TeV $\gamma$-ray morphology.Comment: 5 pages, 3 figures, to appear in Astronomy and Astrophysics Letter

A systemic model for differentiating school technology integration

School technology integration rarely begins with school or educator choice. It is part of a wider context where external and internal factors have direct influence on the goals and tools that are adopted over time. The objective of this study is to investigate the systemic conditions that contribute or inhibit the development of different activities by teachers making use of new media. We compiled a list of well-known conditions for technology integration success and mapped these in the historical and culturally bound perspective of activity theory (cultural historical activity theory). We conducted a multiple case study analysis of four schools, public and private. The results point to unique and distinctive scenarios even when homogeneity would be expected, reinforcing the argument that material conditions do not determine pedagogical outcomes nor do they determine changes in practice. Beyond this, the study proposes a methodology that can help elicit tensions in technology integration, pointing to avenues for school development

First detection of a VHE gamma-ray spectral maximum from a Cosmic source: H.E.S.S. discovery of the Vela X nebula

The Vela supernova remnant (SNR) is a complex region containing a number of sources of non-thermal radiation. The inner section of this SNR, within 2 degrees of the pulsar PSR B0833-45, has been observed by the H.E.S.S. gamma-ray atmospheric Cherenkov detector in 2004 and 2005. A strong signal is seen from an extended region to the south of the pulsar, within an integration region of radius 0.8 deg. around the position (RA = 08h 35m 00s, dec = -45 deg. 36' J2000.0). The excess coincides with a region of hard X-ray emission seen by the ROSAT and ASCA satellites. The observed energy spectrum of the source between 550 GeV and 65 TeV is well fit by a power law function with photon index = 1.45 +/- 0.09(stat) +/- 0.2(sys) and an exponential cutoff at an energy of 13.8 +/- 2.3(stat) +/- 4.1(sys) TeV. The integral flux above 1 TeV is (1.28 +/- 0.17 (stat) +/- 0.38(sys)) x 10^{-11} cm^{-2} s^{-1}. This result is the first clear measurement of a peak in the spectral energy distribution from a VHE gamma-ray source, likely related to inverse Compton emission. A fit of an Inverse Compton model to the H.E.S.S. spectral energy distribution gives a total energy in non-thermal electrons of ~2 x 10^{45} erg between 5 TeV and 100 TeV, assuming a distance of 290 parsec to the pulsar. The best fit electron power law index is 2.0, with a spectral break at 67 TeV.Comment: 5 pages, 4 figures, accepted for publication in Astronomy and Astrophysics letter

Observations of Mkn 421 in 2004 with H.E.S.S. at large zenith angles

Mkn 421 was observed during a high flux state for nine nights in April and May 2004 with the fully operational High Energy Stereoscopic System (H.E.S.S.) in Namibia. The observations were carried out at zenith angles of 60$^\circ$--65$^\circ$, which result in an average energy threshold of 1.5 TeV and a collection area reaching 2~km$^2$ at 10~TeV. Roughly 7000 photons from Mkn~421 were accumulated with an average gamma-ray rate of 8 photons/min. The overall significance of the detection exceeds 100 standard deviations. The light-curve of integrated fluxes above 2~TeV shows changes of the diurnal flux up to a factor of 4.3. For nights of high flux, intra-night variability is detected with a decay time of less than 1 hour. The time averaged energy spectrum is curved and is well described by a power-law with a photon index \egamm and an exponential cutoff at \ecut~TeV and an average integral flux above 2~TeV of 3 Crab flux units. Significant variations of the spectral shape are detected with a spectral hardening as the flux increases. Contemporaneous multi-wavelength observations at lower energies (X-rays and gamma-rays above $\approx 300$~GeV) indicate smaller relative variability amplitudes than seen above 2~TeV during high flux state observed in April 2004.Comment: 5 pages, 4 figures, published in A&

Discovery of the Binary Pulsar PSR B1259-63 in Very-High-Energy Gamma Rays around Periastron with H.E.S.S

We report the discovery of very-high-energy (VHE) gamma-ray emission of the binary system PSR B1259-63/SS 2883 of a radio pulsar orbiting a massive, luminous Be star in a highly eccentric orbit. The observations around the 2004 periastron passage of the pulsar were performed with the four 13 m Cherenkov telescopes of the H.E.S.S. experiment, recently installed in Namibia and in full operation since December 2003. Between February and June 2004, a gamma-ray signal from the binary system was detected with a total significance above 13 sigma. The flux was found to vary significantly on timescales of days which makes PSR B1259-63 the first variable galactic source of VHE gamma-rays observed so far. Strong emission signals were observed in pre- and post-periastron phases with a flux minimum around periastron, followed by a gradual flux decrease in the months after. The measured time-averaged energy spectrum above a mean threshold energy of 380 GeV can be fitted by a simple power law F_0(E/1 TeV)^-Gamma with a photon index Gamma = 2.7+-0.2_stat+-0.2_sys and flux normalisation F_0 = (1.3+-0.1_stat+-0.3_sys) 10^-12 TeV^-1 cm^-2 s^-1. This detection of VHE gamma-rays provides unambiguous evidence for particle acceleration to multi-TeV energies in the binary system. In combination with coeval observations of the X-ray synchrotron emission by the RXTE and INTEGRAL instruments, and assuming the VHE gamma-ray emission to be produced by the inverse Compton mechanism, the magnetic field strength can be directly estimated to be of the order of 1 G.Comment: 10 pages, 8 figures, accepted in Astronomy and Astrophysics on 2 June 2005, replace: document unchanged, replaced author field in astro-ph entry - authors are all members of the H.E.S.S. collaboration and three additional authors (99+3, see document

3.9 day orbital modulation in the TeV gamma-ray flux and spectrum from the X-ray binary LS 5039

New observations of LS 5039, a High Mass X-ray Binary comprising a massive star and compact object, were carried out with the High Energy Stereoscopic System of Cherenkov Telescopes (H.E.S.S.) in 2005 at very high energy (VHE) gamma-ray energies. These observations reveal that its flux and energy spectrum are modulated with the 3.9 day orbital period of the binary system. This is the first time in gamma-ray astronomy that orbital modulation has been observed, and periodicity clearly established using ground-based gamma-ray detectors. The VHE gamma-ray emission is largely confined to half of the orbit, peaking around the inferior conjunction epoch of the compact object. For this epoch, there is also a hardening of the energy spectrum in the energy range between 0.2 TeV and a few TeV. The flux vs. orbital phase profile provides the first clear indication of gamma-ray absorption via pair production within an astrophysical source, a process which is expected to occur if the gamma-ray production site is situated within ~1 AU of the compact object. Moreover the production region size must be not significantly greater than the binary separation (~0.15 AU). Notably, these constraints are also considerably smaller than the collimated outflows or jets (extending out to ~1000 AU) observed in LS 5039. The spectral hardening could arise from variations with phase in the maximum electron energies, and/or the dominant VHE gamma-ray production mechanism.Comment: 8 pages, 8 figures, accepted for publication in Astronomy & Astrophysic

Surface-Cross-Linked Micelles as Multifunctionalized Organic Nanoparticles for Controlled Release, Light Harvesting, and Catalysis

Surfactant micelles are dynamic entities with a rapid exchange of monomers. By “clicking” tripropargylammonium-containing surfactants with diazide cross-linkers, we obtained surface-cross-linked micelles (SCMs) that could be multifunctionalized for different applications. They triggered membrane fusion through tunable electrostatic interactions with lipid bilayers. Antenna chromophores could be installed on them to create artificial light-harvesting complexes with efficient energy migration among tens to hundreds of chromophores. When cleavable cross-linkers were used, the SCMs could break apart in response to redox or pH signals, ejecting entrapped contents quickly as a result of built-in electrostatic stress. They served as caged surfactants whose surface activity was turned on by environmental stimuli. They crossed cell membranes readily. Encapsulated fluorophores showed enhanced photophysical properties including improved quantum yields and greatly expanded Stokes shifts. Catalytic groups could be installed on the surface or in the interior, covalently attached or physically entrapped. As enzyme mimics, the SCMs enabled rational engineering of the microenvironment around the catalysts to afford activity and selectivity not possible with conventional catalysts