Synthesis and Characterization of Andrographolide Derivatives as Regulators of βAPP Processing in Human Cells

Alzheimer’s disease (AD) is a devastating neurodegenerative disorder, one of the main characteristics of which is the abnormal accumulation of amyloid peptide (Aβ) in the brain. Whereas β-secretase supports Aβ formation along the amyloidogenic processing of the β-amyloid precursor protein (βAPP), α-secretase counterbalances this pathway by both preventing Aβ production and triggering the release of the neuroprotective sAPPα metabolite. Therefore, stimulating α-secretase and/or inhibiting β-secretase can be considered a promising anti-AD therapeutic track. In this context, we tested andrographolide, a labdane diterpene derived from the plant Andrographis paniculata, as well as 24 synthesized derivatives, for their ability to induce sAPPα production in cultured SH-SY5Y human neuroblastoma cells. Following several rounds of screening, we identified three hits that were subjected to full characterization. Interestingly, andrographolide (8,17-olefinic) and its close derivative 14α-(5′,7′-dichloro-8′-quinolyloxy)-3,19-acetonylidene (compound 9) behave as moderate α-secretase activators, while 14α-(2′-methyl-5′,7′-dichloro-8′-quinolyloxy)-8,9-olefinic compounds 31 (3,19-acetonylidene) and 37 (3,19-diol), whose two structures are quite similar although distant from that of andrographolide and 9, stand as β-secretase inhibitors. Importantly, these results were confirmed in human HEK293 cells and these compounds do not trigger toxicity in either cell line. Altogether, these findings may represent an encouraging starting point for the future development of andrographolide-based compounds aimed at both activating α-secretase and inhibiting β-secretase that could prove useful in our quest for the therapeutic treatment of AD.     

Sub-Doppler Rydberg spectroscopy by laser-induced two-step recombination at the ESR

For the first time, laser induced radiative electron capture (LIREC) has been combined with sub-Doppler two-photon spectroscopy between Rydberg states of hydrogen-like argon. This revised version was published online in July 2006 with corrections to the Cover Date.     

Towards direct mass measurements of nobelium at SHIPTRAP

The Penning-trap mass spectrometer SHIPTRAP allows precision mass measurements of rare isotopes produced in fusion-evaporation reactions. In the first period of operation the masses of more than 50 neutron-deficient radionuclides have been measured. In this paper the perspectives for direct mass measurements of rare isotopes around nobelium are discussed and the achievable precision is addressed. The temporal stability of the magnetic field, an important issue for the long measurement times resulting from the low production rates, was investigated and the time-dependent uncertainty due to magnetic field fluctuations was determined. Based on the present performance direct mass measurements of nobelium isotopes are already feasible. With several technical improvements heavier elements between Z=102–105 will be in reach.     

A planar Penning trap

We present a new concept for a Penning trap, which is planar and allows for the implementation of novel confinement techniques. The trap provides confinement perpendicular to its plane by an electric potential minimum while a superimposed magnetic field provides radial confinement. Both the axial position and the depth of the potential minimum can be controlled by the applied voltages. The device is scalable in the sense that an arbitrary number of planar traps can be embedded in one plane thus representing a multitrap array which can be used for particle interaction studies. Switches between different traps in the planar array allow for controlled interactions between the single stored particles.     

Temperature measurement of a single ion in a Penning trap

The present work is concerned with the association of a temperature to a single ion stored in a Penning ion trap. Several methods are described which allow to determine the temperature by measurements of the ions cyclotron and axial trapping frequencies. Recent results of a measurement on a hydrogen-like carbon ion ¹²C^{5 +} by use of mode coupling are presented and possible further applications are discussed.Received: 8 July 2004, Published online: 6 December 2004PACS: 07.20.-n. Thermal instruments and apparatus - 07.20.Dt. Thermometers - 42.50.Lc Quantum fluctuations - 42.50.Vk Mechanical effects of light on ions     

Spectroscopic evidence for pi-pi interaction between poly(diallyl dimethylammonium) chloride and multiwalled carbon nanotubes

The interaction between multiwalled carbon nanotubes (MWCNTs) and aqueous poly(diallyl dimethylammonium) chloride (PDDA) was studied by X-ray photoelectron (XPS) and photoacoustic Fourier transform infrared (PA-FTIR) spectroscopies. We have found that the mild sonication of MWCNTs in aqueous PDDA results in a significant improvement of CNT dispersibility and greatly enhances their adhesion to Au and Si substrates. The MWCNT-PDDA interaction is due to the presence of an unsaturated contaminant in the PDDA chain, as confirmed by both XPS and PA-FTIR, which enters into a pi-pi interaction with the CNTs. Electrostatic group repulsions of the coated CNTs then provide the dispersibility and adhesion.     

The anomalous magnetic moment of the electron in hydrogenlike ions

The precise determination of the anomalous magnetic moment of the electron bound in hydrogen-like ions allows for a stringent test of quantum electrodynamics (QED)in the presence of strong electric fields. g-factor measurements on the electron bound in hydrogen-like ions ¹²C⁵⁺ and ¹⁶O⁷⁺, using single ions confined in a Penning trap, have yielded values in agreement with theory on the ppb level. If the QED calculations are considered correct, the results can in turn be used for a determination of fundamental constants like the electron mass m_e, the fine structure constant α or nuclear parameters. We report about presentdevelopments towards g-factor measurements also in medium-heavy and heavy highly-charged ions.     

A Possible New Value for the Electron Mass from g-Factor Measurements on Hydrogen-Like Ions

The mass of the electron in atomic units (m _e) represents the largest error contribution in an experiment to determine the g-factor of the electron bound in hydrogen-like carbon. Recent progress in the calculation reduces the uncertainty of the theoretical value to such a low value that m _e can be determined from a comparison of experimental and theoretical g-factors. The present preliminary value of the electron mass agrees with the accepted value but reduces the uncertainty by about a factor 2. This revised version was published online in July 2006 with corrections to the Cover Date.     

Design of a lattice-matched III–V–N/Si photovoltaic tandem cell monolithically integrated on silicon substrate

In this paper, we present a comprehensive study of high efficiencies tandem solar cells monolithically grown on a silicon substrate using GaAsPN absorber layer. InGaAs(N) quantum dots and GaAsPN quantum wells have been grown recently on GaP/Si susbstrate for applications related to light emission. For photovoltaic applications, we consider the GaAsPN diluted nitride alloy as the top junction material due to both its perfect lattice matching with Si and ideal bandgap energy for current generation in association with the Si bottom cell. Numerical simulation of the top cell is performed. The effect of layer thicknesses and doping on the cell efficiency are evidenced. In these structures a tunnel junction (TJ) is needed to interconnect both the top and bottom sub-cells. We compare the simulated performances of different TJ structures and show that the GaP(n+)/Si(p+) TJ is promising to improve performances of the current–voltage characteristic.