Spectroscopic Investigation of the Effect of Microstructure and Energetic Offset on the Nature of Interfacial Charge Transfer States in Polymer: Fullerene Blends.

Despite performance improvements of organic photovoltaics, the mechanism of photoinduced electron-hole separation at organic donor-acceptor interfaces remains poorly understood. Inconclusive experimental and theoretical results have produced contradictory models for electron-hole separation in which the role of interfacial charge-transfer (CT) states is unclear, with one model identifying them as limiting separation and another as readily dissociating. Here, polymer-fullerene blends with contrasting photocurrent properties and enthalpic offsets driving separation were studied. By modifying composition, film structures were varied from consisting of molecularly mixed polymer-fullerene domains to consisting of both molecularly mixed and fullerene domains. Transient absorption spectroscopy revealed that CT state dissociation generating separated electron-hole pairs is only efficient in the high energy offset blend with fullerene domains. In all other blends (with low offset or predominantly molecularly mixed domains), nanosecond geminate electron-hole recombination is observed revealing the importance of spatially localized electron-hole pairs (bound CT states) in the electron-hole dynamics. A two-dimensional lattice exciton model was used to simulate the excited state spectrum of a model system as a function of microstructure and energy offset. The results could reproduce the main features of experimental electroluminescence spectra indicating that electron-hole pairs become less bound and more spatially separated upon increasing energy offset and fullerene domain density. Differences between electroluminescence and photoluminescence spectra could be explained by CT photoluminescence being dominated by more-bound states, reflecting geminate recombination processes, while CT electroluminescence preferentially probes less-bound CT states that escape geminate recombination. These results suggest that apparently contradictory studies on electron-hole separation can be explained by the presence of both bound and unbound CT states in the same film, as a result of a range of interface structures.

CATALOGIC 301C model - validation and improvement.

In Europe, REACH legislation encourages the use of alternative in silico methods such as (Q)SAR models. According to the recent progress of Chemical Substances Control Law (CSCL) in Japan, (Q)SAR predictions are also utilized as supporting evidence for the assessment of bioaccumulation potential of chemicals along with read across. Currently, the effective use of read across and QSARs is examined for other hazards, including biodegradability. This paper describes the results of external validation and improvement of CATALOGIC 301C model based on more than 1000 tested new chemical substances of the publication schedule under CSCL. CATALOGIC 301C model meets all REACH requirements to be used for biodegradability assessment. The model formalism built on scientific understanding for the microbial degradation of chemicals has a well-defined and transparent applicability domain. The model predictions are adequate for the evaluation of the ready degradability of chemicals.

QSAR Toolbox - workflow and major functionalities.

The OECD QSAR Toolbox is a software application intended to be used by governments, the chemical industry and other stakeholders in filling gaps in (eco)toxicity data needed for assessing the hazards of chemicals. The development and release of the Toolbox is a cornerstone in the computerization of hazard assessment, providing an 'all inclusive' tool for the application of category approaches, such as read-across and trend analysis, in a single software application, free of charge. The Toolbox incorporates theoretical knowledge, experimental data and computational tools from various sources into a logical workflow. The main steps of this workflow are substance identification, identification of relevant structural characteristics and potential toxic mechanisms of interaction (i.e. profiling), identification of other chemicals that have the same structural characteristics and/or mechanism (i.e. building a category), data collection for the chemicals in the category and use of the existing experimental data to fill the data gap(s). The description of the Toolbox workflow and its main functionalities is the scope of the present article.

Ghrelin signaling in human mesenteric arteries.

The hypothesis is that the ghrelin signal pathway consists of new participants including a local second mediator in human mesenteric arteries. The contractile force of isometric artery preparations was measured using a wire-myograph. Whole-cell patch clamp experiments were performed on freshly isolated single smooth muscle cells from the same tissue. After the addition of ghrelin (100 nmol) the outward potassium currents conducted through iberiotoxin-sensitive calcium-activated potassium channels with a large conductance were almost entirely abolished. The effect of ghrelin on potassium currents was insensitive to selective inhibitors of cAMP-dependent protein kinase and soluble guanylate cyclase, but was eliminated in the presence of des-octanoyl ghrelin and O-(octahydro-4,7-methano-1H-inden-5-yl) carbonopotassium dithioate (D-609). Ghrelin dose-dependently increased the force of contraction of native, endothelium-denuded and mostly of endothelium-denuded and treated with tetrodotoxin human mesenteric arteries preconstricted with 1 nmol endothelin-1. This effect of ghrelin was blocked when the bath solution contained 1,4-diamino-2,3-dicyano-1,4-bis(2-aminophenylthio)butadiene (U0126), 4-amino-5-(4-methylphenyl)-7-(t-butyl) pyrazolo[3,4-d] pyrimidine (PP2), D-609, 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl) maleimide (GF109203x), pertussis toxin, 2-aminoethyl diphenylborinate (2-APB), indomethacin, (5Z,13E)-(9S,11S,15R)-9,15,Dihydroxy-11-fluoro-15-(2-indanyl)-16,17,18,19,20,pentanor-5,13-prostadienoic acid (AL-8810) - a non-selective prostanoid receptor antagonist, 5-(4-Chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl pyrazolo (SC-560) - a selective cyclooxygenase 1 inhibitor, ozagrel - a selective thromboxane A(2) synthase inhibitor or T prostanoid receptor antagonist GR32191B. It is concluded that ghrelin increases the force of contraction of human mesenteric arteries by a novel mechanism that involves Src kinase, mitogen-activated protein kinase kinase (MEK), cyclooxygenase 1 and T prostanoid receptor agonist, most probably thromboxane A(2).

POPs: a QSAR system for developing categories for persistent, bioaccumulative and toxic chemicals and their metabolites.

This paper presents the framework of a QSAR-based decision support system which provides a rapid screening of potential hazards, classification of chemicals with respect to risk management thresholds, and estimation of missing data for the early stages of risk assessment. At the simplest level, the framework is designed to rank hundreds of chemicals according to their profile of persistence, bioaccumulation potential and toxicity often called the persistent organic pollutant (POP) profile or the PBT (persistent bioaccumulative toxicant) profile. The only input data are the chemical structure. The POPs framework enables decision makers to introduce the risk management thresholds used in the classification of chemicals under various authorities. Finally, the POPs framework advances hazard identification by integrating a metabolic simulator that generates metabolic map for each parent chemical. Both the parent chemicals and plausible metabolites are systematically evaluated for metabolic activation and POPs profile.

Non-linear modeling of bioconcentration using partition coefficients for narcotic chemicals.

Bioconcentration factors (BCFs) have traditionally been used to describe the tendency of chemicals to concentrate in aquatic organisms. A reexamination of the log-log QSAR between the BCF and Kow for non-congener narcotic chemicals is presented on the basis of recommended data for fish. The model is extended to give a simple correlation between BCF and the toxicity of highly, moderately and weakly hydrophilic chemicals. For the first time, in this study an equation for calculating BCF was applied in a QSAR model for predicting the acute toxicity of chemicals to aquatic organisms.

Expression of BRCA1, NBR1 and NBR2 genes in human breast cancer cells.

BRCA1 is a tumour suppressor gene with a caretaker function in the DNA-damage repair and the maintenance of genome integrity. The human BRCA1 and NBR2 genes and the homologous Brcal and Nbr1 mouse genes are situated head-to-head on human chromosome 17q21 and on mouse chromosome 11, respectively. Their transcription start sites, located on opposite DNA strands, are separated by 218 bp in humans, and by 289 bp in mice. Because of this intimate contact and because of our previous observation of a quasi-reciprocal expression pattern of Brca1 and Nbr1 in mouse spermatogenesis, we estimated here the relative mRNA expression of BRCA1, NBR1 (next-to-BRCA1) and NBR2 genes in a panel of permanent cell lines and primary cell cultures derived from human breast cancer or normal mammary tissue. The analysis revealed highly significant downregulation of BRCA1 in 11 out of 12 examined tumour cell lines and primary cell cultures as compared to non-malignant mammary cells. Two isoforms of NBR1(1A) and the classical NBR1(1B) transcripts were found in cells from malignant mammary tissues, all of them downregulated in respect to normal cells. The expression of NBR2 differed, being increased in three permanent tumour cell lines and slightly decreased in all primary breast cancer cell cultures. The in silico analysis revealed two new putative domains of the predicted NBR1 protein, suggesting its role in the ubiquitin pathway. The recent identification of the ubiquitin protein ligase activity of BRCA1 implies a possible functional connection between both genes.

Main components of voltage-sensitive K+ currents of the human colonic smooth muscle cells.

The aim of the present study is to characterize voltage-sensitive macroscopic K+ current (IK) components in freshly isolated human colonic smooth muscle cells. IK components were studied by the conventional whole-cell voltage clamp method. We found two main components of IK. A transient IK component with fast kinetics, IK(fi), activated upon a holding potential of Vh = -80 mV and inactivated completely following a 4-second-long prepulse to 0 mV. IK(fi) was abolished by Vh = -50 mV, as well as by a pipette solution containing 11 mM EGTA. The second, non-inactivating IK component, IK(ni), had comparable amplitudes at Vh = -80 mV and Vh = -50 mV and could not be inactivated completely, even by positive conditioning stimuli. The amplitudes of IK(ni) depended strongly on the Ca2+ entry, while the amplitudes and the time course of IK(fi) were modulated mainly by the intracellular Ca2+ concentration. About 80% of IK(ni) was selectively inhibited by 0.5 microM apamin. IK(fi) was insensitive to apamin and was totally abolished by 20 mM tetraethyl ammonium extracellularly. According to their voltage dependencies, inactivation properties and pharmacological sensitivity to various K+ channels antagonists, these IK components differ from those described in colonic smooth muscle cells of laboratory animals.