Fundamental role of the fostriecin unsaturated lactone and implications for selective protein phosphatase inhibition

Key derivatives and analogues of fostriecin were prepared and examined that revealed a fundamental role for the unsaturated lactone and confirmed the essential nature of the phosphate monoester. Thus, an identical 200-fold reduction in protein phosphatase 2A (PP2A) inhibition is observed with either the saturated lactone (7) or with an analogue that lacks the entire lactone (15). This 200-fold increase in PP2A inhibition attributable to the unsaturated lactone potentially may be due to reversible C269 alkylation within the PP beta12-beta13 active site loop accounting for PP2A/4 potency and selectivity.     

Monitoring intracellular proteins using fluorescence techniques: from protein synthesis and localization to activity

The recent breakthroughs in genomics and proteomics and improvements of optical methods have made it possible to obtain localized, real-time information on intracellular proteins dynamics, through dynamic three-dimensional (3D) maps of the living cell with nanometric resolution of individual molecules. On one side, brighter variants of the Green Fluorescence Protein (GFP) have been engineered that have different excitation and/or emission spectra that better match available light sources. Like their parent molecule, these variants retain their fluorescence when fused to heterologous proteins on the N- and C- terminals, and this binding generally does not affect the functionality of the tagged protein leading the way to their use as an intracellular reporter. On the other side, optical methods have been improved to allow reaching the level of single-molecule detection inside living cells. Nevertheless some limitations exist for the use of GFP variants for probing 3D conformational changes of proteins. First, these variants are fused to the N and/or C terminals of the studied protein, which are generally not the best location to detect conformational changes resulting from the binding to other proteins or enzyme substrates. Then their own relatively large size makes them unusable for tagging small proteins. These limitations suggest that new tagging processes, permitting the location of the right fluorescent markers at the right places, must be found to built up inter- and/or intra-molecular rulers allowing one to monitor conformational changes resulting from intracellular protein-protein, protein-membrane, and enzyme-substrate binding. These specific locations can be obtained from in vitro studies of 3D conformational changes that occur during protein docking.     

Exact excitation spectrum of the Zn + 1 × Zn + 1 generalized Heisenberg model

We describe the excitations of the generalization of the Heisenberg anisotropic hamiltonian to Z_{n + 1} spins. We analyse the Bethe ansatz equations without assuming the existence of strings. Excited states above an antiferromagnetic ground state are described by a finite number of parameters, which verify system of equations. We give the energy and momentum of the excitations. In a suitable limit we recover the spectrum of a relativistically invariant theory.     

Quantized dispersion of two-dimensional magnetoplasmons detected by photoconductivity spectroscopy

We find that the long-wavelength magnetoplasmon, resistively detected by photoconductivity spectroscopy in high-mobility two-dimensional electron systems, deviates from its well-known semiclassical nature as uncovered in conventional absorption experiments. A clear filling-factor dependent plateau-type dispersion is observed that reveals a so far unknown relation between the magnetoplasmon and the quantum Hall effect.     

Alternating layer and island growth of Pb on Si by spontaneous quantum phase separation

Real-time in situ x-ray studies of continuous Pb deposition on Si(111)-(7x7) at 180 K reveal an unusual growth behavior. A wetting layer forms first to cover the entire surface. Then islands of a fairly uniform height of about five monolayers form on top of the wetting layer and grow to fill the surface. The growth then switches to a layer-by-layer mode upon further deposition. This behavior of alternating layer and island growth can be attributed to spontaneous quantum phase separation based on a first-principles calculation of the system energy.     

Exact solution of the Zn+1 × Zn+1 symmetric generalization of the XXZ model

We give a generalization of the XXZ model where the spin takes n + 1 values, and the hamiltonian is not parity invariant. The diagonalization problem is solved exactly by the use of the n nested Bethe ansatz. We compute the ground-state energy in both the ferromagnetic and the antiferromagnetic case.     

A rutherford scattering study of the diffusion of heavy metal impurities in silicon to ion-damaged surface layers

Rutherford backscattering of 1.75 and 2 MeV ⁴He⁺ ions has been utilized to study the high temperature gettering of Fe, Co, Ni, Cu and Au from silicon by ion-damaged surface layers. In a typical experiment a metal film was evaporated onto one side of a silicon wafer (125 microm thick) which had received ion implantation damage (10¹⁶/cm² Si⁺ ions at 100 keV) on the opposite side; the wafer was then annealed at 900°C, usually for 30 min. The results of such experiments show that the metals studied may be divided into two classes, those which are gettered slowly - Fe, Co, and Au, and those gettered rapidly - Cu and Ni. Fe, Co, and Au were found at levels of 1×10¹³?1×10¹⁴/cm² in the damaged layer, whereas Cu and Ni appeared at levels of 6×10¹⁴ to 5 ×10¹⁶cm². The gettered level of Au, one of the “slow” group, was increased ten-fold by an equal increase in the anneal time to 300 min. The gettered Cu and Au exhibited double peaks in the scattered ion spectra, corresponding to metal concentrated at the most heavily damaged region (end of range for Si implant) and also at the outer surface, with a separation of ~ 1300 Å. A simple model is proposed to explain the slow and fast gettering, based on published interstitial diffusivities and solubilities of the five elements studied.Rutherford scattering has proven to be well suited for the quantitative identification of low levels of impurities on Si surfaces and for impurities gettered at damaged layers close to the surface.     

Tomography of injection and acceleration of monoenergetic electrons in a laser-wakefield accelerator

A tomographic diagnosis method was developed to systematically resolve the injection and acceleration processes of a monoenergetic electron beam in a laser-wakefield accelerator. It was found that all the monoenergetic electrons are injected at the same location in the plasma column and accelerated from 5 to 55 MeV energy in 200 microm distance. This is a direct measurement of the real acceleration gradient in a laser-wakefield accelerator, and the experimental data are consistent with the model of transverse wave breaking and beam loading for monoenergetic electron injection.     

Multiphoton double ionization of Ar in intense extreme ultraviolet laser fields studied by shot-by-shot photoelectron spectroscopy

Photoelectron spectroscopy has been performed to study the multiphoton double ionization of Ar in an intense extreme ultraviolet laser field (hν ～ 21 eV, ～ 5 TW/cm2), by using a free electron laser (FEL). Three distinct peaks identified in the observed photoelectron spectra clearly show that the double ionization proceeds sequentially via the formation of Ar(+): Ar+hν→Ar (+) + e? and Ar2(+) + 2hν→Ar(+) + e?. Shot-by-shot recording of the photoelectron spectra allows simultaneous monitoring of FEL spectrum and the multiphoton process for each FEL pulse, revealing that the two-photon ionization from Ar(+) is significantly enhanced by intermediate resonances in Ar(+).