Poly(dimethylsiloxane) hollow Abbe prism with microlenses for detection based on absorption and refractive index shift

In this paper we report on an optical detection method that utilizes two physical effects for signal transduction, namely absorption and shift of refractive index. The device consists of a hollow prism and was fabricated by means of soft-lithography. It exhibits a high degree of monolithic integration. In order to keep down the amount of external equipment that is necessary to run the device, we were able to integrate several functions, such as focussing of light and alignment of optical fibres. Since all components are fabricated in the same material and in the same process, compatibility with other microfluidic devices or components can be achieved easily. The functional efficiency and the performance of the detector were tested by investigating solutions containing fluorescein, with concentrations between 5 and 1000 microM. The results clearly show the two regions in which the two physical effects are effective.     

Single-shot electron-beam bunch length measurements

We report subpicosecond electro-optic measurements of the length of individual relativistic electron bunches. The longitudinal electron-bunch shape is encoded electro-optically on to the spectrum of a chirped laser pulse. The electron-bunch length is determined by analyzing individual laser-pulse spectra obtained with and without the presence of an electron bunch. Since the length of the chirped laser pulse can be easily changed, the electron bunch can be visualized on different time scales. This single-shot imaging technique is a promising method for real-time electron-bunch diagnostics.     

The Beryllium tetramer: profiling an elusive molecule

The structure and energetics of Be(4) are investigated using state-of-the-art coupled-cluster methods. We compute the optimized bond length, dissociation energy, and anharmonic vibrational frequencies. A composite approach is employed, starting from coupled-cluster theory with single, double, and perturbative triple excitations extrapolated to the complete basis set (CBS) limit using Dunning's correlation consistent cc-pCVQZ and cc-pCV5Z basis sets. A correction for full triple and connected quadruple excitations in the smaller cc-pCVDZ basis set is then added, yielding an approximation to CCSDT(Q)/CBS denoted c～CCSDT(Q). Corrections are included for relativistic and non-Born-Oppenheimer effects. We obtain D(e) = 89.7 kcal mol(-1), D(0) = 84.9 kcal mol(-1), and r(e) = 2.043 A?. Second-order vibrational perturbation theory (VPT2) is applied to a full quartic force field computed at the c～CCSDT(Q) level of theory, yielding B(e) = 0.448 cm(-1) and fundamental frequencies of 666 (a(1)), 468 (e), and 571 (t(2)) cm(-1). Computations on the spectroscopically characterized Be(2) molecule are reported for the purpose of benchmarking our methods. Perturbative estimates of the effect of quadruple excitations are found to be essential to computing accurate parameters for Be(2); however, they seem to exert a much smaller influence on the structure and energetics of Be(4). Our extensive characterization of the Be(4) bonding potential energy surface should aid in the experimental identification of this thermodynamically viable but elusive molecule.     

Anharmonic rovibrational analysis for disilacyclopropenylidene (Si2CH2)

The global minimum on the Si(2)CH(2) electronic singlet potential energy surface has been theoretically predicted to be a peculiar hydrogen bridged (Si···H···Si) disilacyclopropenylidene structure (Si(2)CH(2)). An accurate quartic force field for Si(2)CH(2) has been determined employing ab initio coupled-cluster theory with single and double excitations and a perturbative treatment for triple excitations [CCSD(T)], in combination with the correlation consistent core-valence quadruple zeta (cc-pCVQZ) basis set. The vibration-rotation coupling constants, equilibrium and zero-point vibration corrected rotational constants, centrifugal distortion constants, and harmonic and fundamental vibrational frequencies for six isotopologues of Si(2)CH(2) are predicted using vibrational second-order perturbation theory (VPT2). The anharmonic corrections for the vibrational motions involving the H bridged bonds are found to be more than 5% with respect to the corresponding harmonic vibrational frequencies. In this light, an experimental detection and characterization of disilacyclopropenylidene (Si(2)CH(2)) is highly desired.     

Image‐Based Morphological Profiling Identifies a Lysosomotropic,Iron‐Sequestering Autophagy Inhibitor

Chemical proteomics is widely applied in small‐molecule target identification. However, in general it does not identify non‐protein small‐molecule targets, and thus, alternative methods for target identification are in high demand. We report the discovery of the autophagy inhibitor autoquin and the identification of its molecular mode of action using image‐based morphological profiling in the cell painting assay. A compound‐induced fingerprint representing changes in 579 cellular parameters revealed that autoquin accumulates in lysosomes and inhibits their fusion with autophagosomes. In addition, autoquin sequesters Fe²⁺ in lysosomes, resulting in an increase of lysosomal reactive oxygen species and ultimately cell death. Such a mechanism of action would have been challenging to unravel by current methods. This work demonstrates the potential of the cell painting assay to deconvolute modes of action of small molecules, warranting wider application in chemical biology.     

Effect of pressure on the superconducting transition temperature of doped and neutron-damaged MgB2

Measurements of the superconducting transition temperatures for Al-doped, C-doped and neutron-damaged–annealed MgB₂ samples under pressure up to 8 kbar are presented. The dT_c/dP values change systematically with the decrease of the ambient pressure T_c in a regular fashion. The evolution of the pressure derivatives can be understood assuming that the change in phonon spectrum is a dominant contribution to dT_c/dP.