MASPIT: three-hybrid trap for quantitative proteome fingerprinting of small molecule-protein interactions in mammalian cells

Organic small molecules generally act by perturbing the function of one or more cellular target proteins, the identification of which is essential to an understanding of the molecular basis of drug action. Here we describe the application of methotrexate-linked small molecule ligands to a mammalian three-hybrid interaction trap for proteome-wide identification of small molecule targets, quantification of the targeting potency of unmodified small molecules for such targets in intact cells, and screening for inhibitors of small molecule-protein interactions. During the course of this study we also identified the pyrido[2,3-d]pyrimidine PD173955, a known SRC kinase inhibitor, as a potent inhibitor of several ephrin receptor tyrosine kinases. This finding could perhaps be exploited in the design of inhibitors for this kinase subfamily, members of which have been implicated in the pathogenesis of various diseases, including cancer.     

Self-guiding of infrared and visible light in photonic crystal slabs

We experimentally demonstrate diffractionless guidance and efficient routing of light in two-dimensional photonic crystal slabs at infrared and visible wavelengths. Our particular design allows for simultaneous guidance of TE and TM polarized light beams at the same wavelength. Routing performance and possibilities of propagation loss reduction are investigated experimentally. Experimental results are in excellent agreement with three-dimensional simulations.     

Transmission enhanced optical lenses with self-organized antireflective subwavelength structures for the UV range

We present transmission increased fused silica lenses produced by using self-organized antireflective structures for which we developed an efficient manufacturing process. The spectral transmission measured over the whole lens aperture shows a significant transmission enhancement of up to 3.5% in the UV range. Local measurements on the lens's surface reveal a strongly reduced reflection of below 0.1% for 300 nm wavelength, which is homogeneous over the whole lens. Further, the lenses show a broadband spectral antireflection behavior. For 600 nm wavelength the reflection was measured at about 1%.     

Hollow-fiber compression of 6 mJ pulses from a continuous-wave diode-pumped single-stage Yb,Na:CaF2 chirped pulse amplifier

Here, 200 fs 6 mJ pulses from a cw diode-pumped Yb,Na:CaF(2) amplifier are spectrally broadened in an Ar- or Ne-filled hollow-core fiber and recompressed to 20 fs (Ar) and 35 fs (Ne) using a prism pair. The results of spectral broadening and phase measurement are in excellent agreement with numerical modeling based on the generalized nonlinear Schr?dinger equation. The longer laser wavelength of 1030 nm permits favorable energy scaling for the hollow-fiber technique compared to ultrafast amplifiers operating at 800 nm.     

Effects of anisotropic disorder in an optical metamaterial

We consider the effect of disorder in one transverse dimension, termed anisotropic disorder, on the optical properties of a metamaterial consisting of cut-wire-pair meta-atoms. The work comprises experimental and numerical studies. The appropriate samples were fabricated and their optical properties quantified in the far-field. For comparison large-scale rigorous numerical simulations were performed. We observe excellent agreement between experiment and theory. Based on our results we reveal how the electric dipole interactions between adjacent meta-atoms affect the overall spectral response of the metamaterial. Our main observation is a polarization-sensitive degradation of the symmetric resonance for anisotropic disorder.     

The motions of hydrogen impurities in α-Palladium-hydride

The intensity distribution of inelastically scattered thermal and hot neutrons on hydrogen impurities in α-palladium hydride has been studied as a function of concentration, temperature, momentum transfer and different annealing procedures. In up-scattering experiments the first and second harmonics appear at E₁^H = (66 ± 4) me V and E₂^H = (135 ± 15) meV respectively, and the hydrogen band modes have a frequency distribution as expected from measured dispersion curves for pure palladium. For deuterium the first harmonic appears at E₁^D = (48 ± 4) meV. The width of the hydrogen local mode E₁^H changes from 30 to 20 me V and its position from 63 to 66 meV, when the hydrogen concentration is altered from 2.7 to 0.2 at.%. After an extended annealing procedure and at the lowest concentration of 0.2 at.%, the local mode appears in down-scattering experiments at E₁^H = (68.5 ± 2) meV with a full width at half height ΔE₁^H = 4 meV, which is purely instrumental. For higher concentrations and insufficient annealing of the sample, cluster of hydrogen atoms are formed even in the α-phase, as indicated by the increasing width of the local mode. The peak intensity of the E₁^H mode decreases upon changing the temperature from 423 to 673°K. Upon changing the direction of the k-vector from the [1,0,0]- to the [1,1,0]-direction, the peak intensity of the local mode decreases by a factor of ten. These observations indicate the existence of anhannonic effects along the [l,l,0]-direction.     

High-average-power femtosecond fiber chirped-pulse amplification system

Efficient generation of 76-W average power of 400-fs pulses at 75-MHz repetition rate by use of a diode-pumped ytterbium-doped double-clad fiber-based chirped-pulse amplification system is demonstrated. The key element in the system is a diffraction grating compressor consisting of highly efficient transmission gratings in fused silica, allowing recompression at this high power level.     

A central conservative scheme for general rectangular grids

We present an extension of the genuinely multi-dimensional semi-discrete central scheme developed in [A. Kurganov, S. Noelle, G. Petrova, Semidiscrete central-upwind schemes for hyperbolic conservation laws and Hamilton–Jacobi equations, SIAM J. Sci. Comput. 23 (3) (2001) 707–740.] to arbitrary orthogonal grids. The presented algorithm is constructed to yield the geometric scaling factors in a self-consistent way.Additionally, the order of the scheme is not fixed during the derivation of the basic algorithm. Based on the resulting general scheme it is possible to construct methods of any desired order, just by considering the corresponding reconstruction polynomial. We demonstrate how a second order scheme in plane polar coordinates and cylindrical coordinates can be derived from our general formulation. Finally, we demonstrate the correctness of this second order scheme through application to several numerical experiments.     

High performance diffraction gratings made by e-beam lithography

Gratings are essential components in different high performance optical set-ups such as spectrometers in space missions or ultrashort-pulse laser compression arrangements. Often such kinds of applications require gratings operating close to the technological accessible limits of today??s fabrication technology. Typical critical parameters are the diffraction efficiency and its polarization dependency, the wave-front error introduced by the grating, and the stray-light performance. Additionally, space applications have specific environmental requirements and laser application typically demand a high damage threshold. All these properties need to be controlled precisely on rather large grating areas. Grating sizes of 200?mm or even above are not unusual anymore. The paper provides a review on how such high performance gratings can be realized by electron-beam lithography and accompanying technologies. The approaches are demonstrated by different examples. The first example is the design and fabrication of the grating for the Radial-Velocity-Spectrometer of the GAIA-mission of the ESA. The second grating is a reflective pulse compression element with no wavelength resonances due to an optimized design. The last example shows a three level blazed grating in resonance domain with a diffraction efficiency of approximately 86?%.     

External-cavity diode laser in second-order Littrow configuration

In this Letter, we propose and demonstrate an external-cavity diode laser in second-order Littrow configuration. This topology utilizes a low-efficiency diffraction grating to establish a high-finesse external cavity, strong optical feedback, a high polarization discrimination, and a circular TEM₀₀ output mode. In our proof-of-concept experiment, we realized a cavity with a finesse of 1855, being, to the best of our knowledge, the highest value ever reported for a three-port-grating-coupled cavity. With optical feedback, the laser threshold of the laser diode employed was reduced by a factor of 4.