Selective Pharmacophore Models of Dopamine D1 and D2 Full Agonists Based on Extended Pharmacophore Features

This study is focused on the identification of structural features that determine the selectivity of dopamine receptor agonists toward D₁ and D₂ receptors. Selective pharmacophore models were developed for both receptors. The models were built by using projected pharmacophoric features that represent the main agonist interaction sites in the receptor (the Ser residues in TM5 and the Asp in TM3), a directional aromatic feature in the ligand, a feature with large positional tolerance representing the positively charged nitrogen in the ligand, and sets of excluded volumes reflecting the shapes of the receptors. The sets of D₁ and D₂ ligands used for modeling were carefully selected from published sources and consist of structurally diverse, conformationally rigid full agonists as active ligands together with structurally related inactives. The robustness of the models in discriminating actives from inactives was tested against four ensembles of conformations generated by using different established methods and different force fields. The reasons for the selectivity can be attributed to both geometrical differences in the arrangement of the features, e.g., different tilt angels of the π system, as well as shape differences covered by the different sets of excluded volumes. This work provides useful information for the design of new D₁ and D₂ agonists and also for comparative homology modeling of D₁ and D₂ receptors. The approach is general and could therefore be applied to other ligand–protein interactions for which no experimental protein structure is available.     

Inhibition of Human DHODH by 4‐Hydroxycoumarins,Fenamic Acids,and N‐(Alkylcarbonyl)anthranilic Acids Identified by Structure‐Guided Fragment Selection

A strategy that combines virtual screening and structure‐guided selection of fragments was used to identify three unexplored classes of human DHODH inhibitor compounds: 4‐hydroxycoumarins, fenamic acids, and N‐(alkylcarbonyl)anthranilic acids. Structure‐guided selection of fragments targeting the inner subsite of the DHODH ubiquinone binding site made these findings possible with screening of fewer than 300 fragments in a DHODH assay. Fragments from the three inhibitor classes identified were subsequently chemically expanded to target an additional subsite of hydrophobic character. All three classes were found to exhibit distinct structure–activity relationships upon expansion. The novel N‐(alkylcarbonyl)anthranilic acid class shows the most promising potency against human DHODH, with IC₅₀ values in the low nanomolar range. The structure of human DHODH in complex with an inhibitor of this class is presented.     

Tailoring side chains of low band gap polymers for high efficiency polymer solar cells

High efficiency organic solar cells (OSCs) require conjugated polymers with a low band gap, broad absorption in visible and IR region, high carrier mobility, and relatively high molecular weight as p-type donor materials. Flexible side chains on the rigid polymer backbone are crucial for the solubility of conjugated polymers. In this work, four polymers with the main chain structure of fluorene-thiophene-benzothiadiazole-thiophene and flexible side chains located on fluorene, thiophene, and benzothiadiazole moiety, respectively, have been synthesized by Suzuki-Miyaura-Schlüter polycondensation. Photovoltaic device measurements with a device configuration of ITO/polymer:PC₇₁BM blends/LiF/Al show that P1 carrying octyloxy chains on benzothiadiazole rings gives the best performance, with a power conversion efficiency of 3.1%.     

Tetranorsesquiterpenoids as Attractants of Yucca Moths to Yucca Flowers

Journal of Chemical Ecology - The obligate pollination mutualism between Yucca and yucca moths is a classical example of coevolution. Oviposition and active pollination by female yucca moths occur...     

Key technologies for IMT-advanced mobile communication systems

WINNER is an ambitious research project aiming at identification, development, and assessment of key technologies for IMTAdvanced mobile communication systems. WINNER has devised an OFDMA-based system concept with excellent system-level performance for flexible deployments in a wide variety of operating conditions. The WINNER system provides a significant step forward from current 3G systems. Key innovations integrated into the system concept include flexible spectrum usage and relaying, adaptive advanced antenna schemes and pilot design, close to optimal link adaptation, hierarchical control signaling, and a highly flexible multiple access scheme. The end-to-end performance assessment results demonstrate that the WINNER concept meets the IMTAdvanced requirements.     

On optimality in auditory information processing

We study limits for the detection and estimation of weak sinusoidal signals in the primary part of the mammalian auditory system using a stochastic Fitzhugh-Nagumo model and an action-recovery model for synaptic depression. Our overall model covers the chain from a hair cell to a point just after the synaptic connection with a cell in the cochlear nucleus. The information processing performance of the system is evaluated using so-called phi-divergences from statistics that quantify "dissimilarity" between probability measures and are intimately related to a number of fundamental limits in statistics and information theory (IT). We show that there exists a set of parameters that can optimize several important phi-divergences simultaneously and that this set corresponds to a constant quiescent firing rate (QFR) of the spiral ganglion neuron. The optimal value of the QFR is frequency dependent but is essentially independent of the amplitude of the signal (for small amplitudes). Consequently, optimal processing according to several standard IT criteria can be accomplished for this model if and only if the parameters are "tuned" to values that correspond to one and the same QFR. This offers a new explanation for the QFR and can provide new insight into the role played by several other parameters of the peripheral auditory system.     

Interaction between local and overall buckling

Numerical solutions of the equations governing the interaction of local and overall modes on box columns are presented. In confirmation of previous results these solutions show that elastic buckling is highly sensitive to changes in the magnitude of both local and overall small imperfections, and that the strong optimum indicated for coincident mode design is effectively eliminated when this imperfection sensitivity as well as effects of plasticity are included. It is also clearly demonstrated that the reduced modulus approach provides a conservative estimate of the elastic load-carrying capacity.The inclusion of plasticity into the analysis shows that the effects of elastic interaction may also be highly significant in controlling the plastic collapse load, and for most practical cases this plastic interactive buckling will control design. An extension of the Perry-Robertson procedure is shown to provide a convenient means of presenting the design information. Finally, the usefulness of the van der Neut model as the starting point of the analysis is verified.     

Use or disposal of by-products and spent material from the vegetable oil processing industry in Europe

The tendency in the oil and fat industry in Europe as far as by-products and spent material are concerned is to use and regenerate as much as possible for chemical-technical purposes. Materials with a high thermal value which are not suitable or profitable for use in chemical-technical products will in the future probably be utilized as a fuel in combination with fuel oil. By-products and spent material that cannot be exploited in the manners outlined above will be deposited in dumps. Incineration is another possibility. However, the quantities of waste must be of a considerable magnitude if this method is not to be too expensive.