A surface-bound molecule that undergoes optically biased Brownian rotation.

Developing molecular systems with functions analogous to those of macroscopic machine components, such as rotors, gyroscopes and valves, is a long-standing goal of nanotechnology. However, macroscopic analogies go only so far in predicting function in nanoscale environments, where friction dominates over inertia. In some instances, ratchet mechanisms have been used to bias the ever-present random, thermally driven (Brownian) motion and drive molecular diffusion in desired directions. Here, we visualize the motions of surface-bound molecular rotors using defocused fluorescence imaging, and observe the transition from hindered to free Brownian rotation by tuning medium viscosity. We show that the otherwise random rotations can be biased by the polarization of the excitation light field, even though the associated optical torque is insufficient to overcome thermal fluctuations. The biased rotation is attributed instead to a fluctuating-friction mechanism in which photoexcitation of the rotor strongly inhibits its diffusion rate.

Positive and negative modulation of group I metabotropic glutamate receptors.

A discriminating pharmacophore model for noncompetitive metabotropic glutamate receptor antagonists of subtype 1 (mGluR1) was developed that facilitated the discovery of moderately active mGluR1 antagonists. One scaffold was selected for the design of several focused libraries where different substitution patterns were introduced. This approach facilitated the discovery of potent mGluR1 antagonists, as well as positive and negative mGluR5 modulators, because both receptor subtypes share similar binding pockets. For mGluR1 antagonists, a homology model of the mGlu1 receptor was established, and a putative binding mode within the receptor's transmembrane domain was visualized.

Novel core-expanded rylenebis(dicarboximide) dyes bearing pentacene units: facile synthesis and photophysical properties.

Two synthetic routes for the benzannulation in the "bay"-region of rylenebis(dicarboximide)s leading to new pi-system-expanded chromophores are described. The first route follows a two-step approach: Suzuki coupling of bromo-substituted perylenebis(dicarboximide) with 2-bromophenylboronic acid, followed by palladium-catalysed dehydrobromination. The second route is best described as a palladium-assisted cycloaddition of benzyne, formed in situ, to the bay-region of the bromo-substituted rylene core. Two new types of core-expanded rylene dyes were synthesised: yellow dibenzocoronenebis(dicarboximide)s, absorbing at 490 nm, and a green dinaphthoquaterrylenebis(dicarboximide), which absorbs at 700 nm. These new chromophores are characterised by significant hypsochromic shifts of absorption, compared to their parent rylenebis(dicarboximide)s, excellent photostabilities and high fluorescence quantum yields.

Expanding benzene to giant graphenes: towards molecular devices.

Phenylene-based conjugated materials provide versatile platforms for the development of molecular devices. Architectures of one- and two-dimensional polyphenylenes, which self-assemble into three-dimensional objects with advantageous electronic properties, have been investigated. Systematic relations between the size, substitution and shape with function were found, which enabled the further optimization of the materials. Hand in hand with the development of suitable methods for visualization and processing, promising results were obtained for performance of nanoscale electronic devices.

Facile synthetic approach to novel core-extended perylene carboximide dyes.

The straightforward synthesis of two new classes of core-extended perylene chromophores, dibenzocoronene tetracarboxdiimide and indenoperylene dicarboxmonoimide, proves that directional enlargement of the aromatic pi-system leads to tailored bathochromic and hypsochromic shifts.

Reducing the time complexity of the derandomized evolution strategy with covariance matrix adaptation (CMA-ES).

This paper presents a novel evolutionary optimization strategy based on the derandomized evolution strategy with covariance matrix adaptation (CMA-ES). This new approach is intended to reduce the number of generations required for convergence to the optimum. Reducing the number of generations, i.e., the time complexity of the algorithm, is important if a large population size is desired: (1) to reduce the effect of noise; (2) to improve global search properties; and (3) to implement the algorithm on (highly) parallel machines. Our method results in a highly parallel algorithm which scales favorably with large numbers of processors. This is accomplished by efficiently incorporating the available information from a large population, thus significantly reducing the number of generations needed to adapt the covariance matrix. The original version of the CMA-ES was designed to reliably adapt the covariance matrix in small populations but it cannot exploit large populations efficiently. Our modifications scale up the efficiency to population sizes of up to 10n, where n is the problem dimension. This method has been applied to a large number of test problems, demonstrating that in many cases the CMA-ES can be advanced from quadratic to linear time complexity.

Comparative sequence and expression analyses of four mammalian VPS4 genes.

The VPS4 gene is a member of the AAA-family; it codes for an ATPase which is involved in lysosomal/endosomal membrane trafficking. VPS4 genes are present in virtually all eukaryotes. Exhaustive data mining of all available genomic databases from completely or partially sequenced organisms revealed the existence of up to three paralogues, VPS4a, -b, and -c. Whereas in the genome of lower eukaryotes like yeast only one VPS4 representative is present, we found that mammals harbour two paralogues, VPS4a and VPS4b. Most interestingly, the Fugu fish contains a third VPS4 paralogue (VPS4c). Sequence comparison of the three VPS4 paralogues indicates that the Fugu VPS4c displays sequence features intermediate between VPS4a and VPS4b. Using complete mammalian VPS4a and VPS4b cDNA clones as probes, genomic clones of both VPS4 paralogues in human and mouse were identified and sequenced. The chromosomal loci of all four VPS4 genes were determined by independent methods. A BLAST search of the human genome database with the human VPS4A sequence yielded a double match, most likely due to a faulty assembly of sequence contigs in the human draft sequence. Fluorescent in situ hybridization and radiation hybrid analyses demonstrated that human and mouse VPS4A/a and VPS4B/b are located on syntenic chromosomal regions. Northern blot and semi-quantitative reverse transcription analyses showed that mouse VPS4a and VPS4b are differentially expressed in different organs, suggesting that the two paralogues have developed different functional properties since their divergence. To investigate the subcellular distribution of the murine VPS4 paralogues, we transiently expressed various fluorescent VPS4 fusion proteins in mouse 3T3 cells. All tested VPS4 fusion proteins were found in the cytosol. Expression of dominant-negative mutant VPS4 fusion proteins led to their concentration in the perinuclear region. Co-expression of VPS4a-GFP and VPS4b-dsRed fusion proteins revealed a partial co-localization that was most prominent with mutant VPS4a and VPS4b proteins. A physical interaction between the mouse paralogues was also supported by two-hybrid analyses.