High-intracavity-power thin-disk laser for the alignment of molecules

We propose a novel approach for strong alignment of gas-phase molecules for experiments at arbitrary repetition rates. A high-intracavity-power continuous-wave laser will provide the necessary ac electric field of $\!10^{10}$- $10^{11}~\text{W}/\text{cm}^2$. We demonstrate thin-disk lasers based on Yb:YAG and Yb:Lu$_2$O$_3$ in a linear high-finesse resonator providing intracavity power levels in excess of 100~kW at pump power levels on the order of 50~W. The multi-longitudinal-mode operation of this laser avoids spatial-hole burning even in a linear standing-wave resonator. The system will be scaled up as in-vacuum system to allow for the generation of fields of $10^{11}~\text{W}/\text{cm}^2$. This system will be directly applicable for experiments at modern X-ray light sources, such as synchrotrons or free-electron lasers, which operate at various very high repetition rates. This would allow to record molecular movies through temporally resolved diffractive imaging of fixed-in-space molecules, as well as the spectroscopic investigation of combined X-ray-NIR strong-field effects of atomic and molecular systems

Stable Chinese Hamster Ovary Suspension Cell Lines Harboring Recombinant Human Cytochrome P450 Oxidoreductase and Human Cytochrome P450 Monooxygenases as Platform for In Vitro Biotransformation Studies

In the liver, phase-1 biotransformation of drugs and other xenobiotics is largely facilitated by enzyme complexes consisting of cytochrome P450 oxidoreductase (CPR) and cytochrome P450 monooxygenases (CYPs). Generated from human liver-derived cell lines, recombinant in vitro cell systems with overexpression of defined phase-1 enzymes are widely used for pharmacological and toxicological drug assessment and laboratory-scale production of drug-specific reference metabolites. Most, if not all, of these cell lines, however, display some background activity of several CYPs, making it difficult to attribute effects to defined CYPs. The aim of this study was to generate cell lines with stable overexpression of human phase-1 enzymes based on Chinese hamster ovary (CHO) suspension cells. Cells were sequentially modified with cDNAs for human CPR in combination with CYP1A2, CYP2B6, or CYP3A4, using lentiviral gene transfer. In parallel, CYP-overexpressing cell lines without recombinant CPR were generated. Successful recombinant expression was demonstrated by mRNA and protein analyses. Using prototypical CYP-substrates, generated cell lines proved to display specific enzyme activities of each overexpressed CYP while we did not find any endogenous activity of those CYPs in parental CHO cells. Interestingly, cell lines revealed some evidence that the dependence of CYP activity on CPR could vary between CYPs. This needs to be confirmed in further studies. Recombinant expression of CPR was also shown to enhance CYP3A4-independent metabolisation of testosterone to androstenedione in CHO cells. We propose the novel serum-free CHO suspension cell lines with enhanced CPR and/or defined CYP activity as a promising “humanised” in vitro model to study the specific effects of those human CYPs. This could be relevant for toxicology and/or pharmacology studies in the pharmaceutical industry or medicine

The velocity dispersion and mass function of the outer halo globular cluster Palomar 4

We obtained precise line-of-sight radial velocities of 23 member stars of the remote halo globular cluster Palomar 4 (Pal 4) using the High Resolution Echelle Spectrograph (HIRES) at the Keck I telescope. We also measured the mass function of the cluster down to a limiting magnitude of V~28 mag using archival HST/WFPC2 imaging. We derived the cluster's surface brightness profile based on the WFPC2 data and on broad-band imaging with the Low-Resolution Imaging Spectrometer (LRIS) at the Keck II telescope. We find a mean cluster velocity of 72.55+/-0.22 km/s and a velocity dispersion of 0.87+/-0.18 km/s. The global mass function of the cluster, in the mass range 0.55<=M<=0.85 M_solar, is shallower than a Kroupa mass function and the cluster is significantly depleted in low-mass stars in its center compared to its outskirts. Since the relaxation time of Pal 4 is of the order of a Hubble time, this points to primordial mass segregation in this cluster. Extrapolating the measured mass function towards lower-mass stars and including the contribution of compact remnants, we derive a total cluster mass of 29800 M_solar. For this mass, the measured velocity dispersion is consistent with the expectations of Newtonian dynamics and below the prediction of Modified Newtonian Dynamics (MOND). Pal 4 adds to the growing body of evidence that the dynamics of star clusters in the outer Galactic halo can hardly be explained by MOND.Comment: 17 pages, accepted for publication in MNRAS; Fig. 8 surface brightness/density data at github.com/matthiasjfrank/pal4_surface_brightnes

Assessment of Arabian Gulf Seaweeds from Kuwait as Sources of Nutritionally Important Polyunsaturated Fatty Acids (PUFAs)

Funding: We are grateful to the Kuwait Institute for Scientific Research (KISR) for PhD funding for H.A.-A. We are thankful to the National Unit for Environmental Research and Services (NUERS) at Kuwait University, Project # SRUIL01/13 and the Department of Marine Sciences for providing their facilities and labs. We equally thank the UK Natural Environment Research Council for their support to F.C.K. (program Oceans 2025–WP 4.5 and grants NE/D521522/1 and NE/J023094/1). This work also received support from the Marine Alliance for Science and Technology for Scotland pooling initiative. MASTS is funded by the Scottish Funding Council (grant reference HR09011) and contributing institutions. PK would like to acknowledge European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 839151 for fundingPeer reviewedPublisher PD

Synthesis of mono Cytochrome P450 in a modified CHO-CPR cell-free protein production platform

Cytochromes P450 (CYPs) are a group of monooxygenases that can be found in almost all kinds of organisms. For CYPs to receive electrons from co-substrate NADPH, the activity of NADPH-Cytochrome-P450-oxidoreductase (CPR) is required as well. In humans, CYPs are an integral part of liver-based phase-1 biotransformation, which is essential for the metabolization of multiple xenobiotics and drugs. Consequently, CYPs are important players during drug development and therefore these enzymes are implemented in diverse screening applications. For these applications it is usually advantageous to use mono CYP microsomes containing only the CYP of interest. The generation of mono-CYP containing mammalian cells and vesicles is difficult since endogenous CYPs are present in many cell types that contain the necessary co-factors. By obtaining translationally active lysates from a modified CHO-CPR cell line, it is now possible to generate mono CYPs in a cell-free protein synthesis process in a straightforward manner. As a proof of principle, the synthesis of active human CYPs from three different CYP450 gene families (CYP1A2, CYP2B6 and CYP3A4), which are of outstanding interest in industry and academia was demonstrated. Luciferase based activity assays confirm the activity of the produced CYPs and enable the individual adaptation of the synthesis process for efficient cell-free enzyme production. Furthermore, they allow for substrate and inhibitor screenings not only for wild-type CYPs but also for mutants and further CYP isoforms and variants. As an example, the turnover of selected CYP substrates by cell-free synthesized CYPs was demonstrated via an indirect luciferase assay-based screening setup

How Do Adults with Autism Spectrum Disorder Participate in the Labor Market? A German Multi-center Survey

International studies show disadvantages for adults with autism spectrum disorder (ASD) in the labor market. Data about their participation in the German labor market are scarce. The aim of this study was to examine the integration of adults with ASD in the German labor market in terms of education, employment and type of occupation by means of a cross-sectional-study, using a postal questionnaire. Findings show above average levels of education for adults with ASD compared to the general population of Germany and simultaneously, below average rates of employment and high rates of financial dependency. That indicates a poor integration of adults with ASD in the German labor market and emphasizes the need for vocational support policies for adults with ASD

Ionization of 1D and 3D oriented asymmetric top molecules by intense circularly polarized femtosecond laser pulses

We present a combined experimental and theoretical study on strong-field ionization of a three-dimensionally oriented asymmetric top molecule, benzonitrile (C$_7$H$_5$N), by circularly polarized, nonresonant femtosecond laser pulses. Prior to the interaction with the strong field, the molecules are quantum-state selected using a deflector, and 3-dimensionally (3D) aligned and oriented adiabatically using an elliptically polarized laser pulse in combination with a static electric field. A characteristic splitting in the molecular frame photoelectron momentum distribution reveals the position of the nodal planes of the molecular orbitals from which ionization occurs. The experimental results are supported by a theoretical tunneling model that includes and quantifies the splitting in the momentum distribution. The focus of the present article is to understand strong-field ionization from 3D-oriented asymmetric top molecules, in particular the suppression of electron emission in nodal planes of molecular orbitals. In the preceding article [Dimitrovski et al., Phys. Rev. A 83, 023405 (2011)] the focus is to understand the strong-field ionization of one-dimensionally-oriented polar molecules, in particular asymmetries in the emission direction of the photoelectrons.Comment: 12 pages, 9 figure