Excitation localization in a trimeric perylenediimide macrocycle: Synthesis, theory, and single molecule spectroscopy.

A novel trimeric perylenediimide (PDI) macrocycle was synthesized, and its intramolecular electronic couplings were investigated by bulk and single-molecule optical spectroscopy and by various theoretical approaches. In polarization-resolved excitation spectroscopy at 1.2 K in a PMMA matrix, the appearance and disappearance of the three zero-phonon lines (ZPLs) of an individual trimer by changing the polarization in steps of 60° nicely reflect an approximate triangular geometry of the macrocycle and indicate localized excitations that are transferred by incoherent hopping processes at time scales of around 1 ps as inferred from the ZPL linewidths. The electronic coupling strength deduced from the low temperature data is found to be in good agreement with theoretical estimates. Bulk spectroscopy in toluene at room temperature indicates that the excitations are also localized under these conditions. Theory reveals that the reasons for the localized nature of the excitations at room and low temperatures are different. For a rigid macrocycle, the excitations are predicted to be delocalized, but molecular dynamics simulations point to considerable structural flexibility at ambient temperatures, which counteracts excitation delocalization. At 1.2 K in a PMMA matrix, this effect is too small to lead to localization. Yet, supported by simple model calculations, the disorder in the PMMA host induces sufficient differences between the PDI chromophores, which again result in localized excitations. By addressing crucial aspects of excitation energy transfer, our combined approach provides a detailed and quantitative account of the interchromophore communication in a trimeric macrocycle.

Conformational Dynamics of the Dengue Virus Protease Revealed by Fluorescence Correlation and Single-Molecule FRET Studies.

The dengue virus protease (DENV-PR) represents an attractive target for counteracting DENV infections. It is generally assumed that DENV-PR can exist in an open and a closed conformation and that active site directed ligands stabilize the closed state. While crystal structures of both the open and the closed conformation were successfully resolved, information about the prevalence of these conformations in solution remains elusive. Herein, we address the question of whether there is an equilibrium between different conformations in solution which can be influenced by addition of a competitive inhibitor. To this end, DENV-PR was statistically labeled by two dye molecules constituting a FRET (fluorescence resonance energy transfer) couple. Fluorescence correlation spectroscopy and photon-burst detection were employed to examine FRET pair labeled DENV-PRs freely diffusing in solution. The measurements were performed with two double mutants and with two dye couples. The data provide strong evidence that an equilibrium of at least two conformations of DENV-PR exists in solution. The competitive inhibitor stabilizes the closed state. Because the open and closed conformations appear to coexist in solution, our results support the picture of a conformational selection rather than that of an induced fit mechanism with respect to the inhibitor-induced formation of the closed state.

Patient handover - the poor relation of medical training?

Objective: The handover of patients to medical colleagues and to members of other professional groups is a central task in the medical care process for patient safety. Nevertheless, little is known about teaching and testing on the subject of handing over. The present article therefore examines the extent to which handover is the subject of teaching and examinations at medical faculties in Germany. Methodology: In 31 medical faculties the teachers were asked about the implementation of the NKLM learning objectives in the area of communication. The survey was conducted within the framework of group interviews with lecturers, in which it was determined whether each learning objective of the NKLM (National Competency-based Catalogue of Learning Objectives in Medicine) on the subject of communication, is explicitly taught in lectures and examinations at the respective faculty. Results: The learning objective "transfer to medical colleagues" is covered by 19 faculties, while the learning objective of interprofessional transfer is covered by 14 faculties. There are examinations for transfer to medical colleagues and interprofessional transfer at two faculties. There is a highly significant relationship between the total number of communicative learning objectives that are put into practice in a faculty and the coverage of the learning objectives for handover. Conclusions: In the field of communications, the subject of handover is less frequently taught at the faculties and, more importantly, it is less frequently examined than other NKLM contents. This is particularly evident in the interprofessional area. The subject is more likely to be taught as a handover between physicians, while the interprofessional interfaces attract less attention. In terms of patient safety, it would be desirable to give a higher priority to the subject of handover. An inter-faculty exchange and the inclusion of the subject of intra- and interprofessional transfer in state examinations could give the implementation process at the faculties a decisive impetus.

Bromide Sources and Loads in Swiss Surface Waters and Their Relevance for Bromate Formation during Wastewater Ozonation.

Bromide measurements and mass balances in the catchments of major Swiss rivers revealed that chemical industry and municipal waste incinerators are the most important bromide sources and account for ∼50% and ∼20%, respectively, of the ∼2000 tons of bromide discharged in the Rhine river in 2014 in Switzerland. About 100 wastewater treatment plants (WWTPs) will upgrade their treatment for micropollutant abatement in the future to comply with Swiss regulations. An upgrade with ozonation may lead to unintended bromate formation in bromide-containing wastewaters. Measured bromide concentrations were <0.05 mg L(-1) in ∼75% of 69 WWTPs, while they ranged from 0.4 to ∼50 mg L(-1) in WWTPs with specific bromide sources (e.g., municipal waste incinerators, landfill leachate, and chemical industry). Wastewater ozonation formed little bromate at specific ozone doses of ≤0.4 mg O3/mg DOC, while the bromate yields were almost linearly correlated to the specific ozone dose for higher ozone doses. Molar bromate yields for typical specific ozone doses in wastewater treatment (0.4-0.6 mg O3/mg DOC) are ≤3%. In a modeled extreme scenario (in which all upgraded WWTPs release 10 µg L(-1) of bromate), bromate concentrations increased by <0.4 µg L(-1) in major Swiss rivers and by several micrograms per liter in receiving water bodies with a high fraction of municipal wastewater.

Multi-level approach for the integrated assessment of polar organic micropollutants in an international lake catchment: the example of Lake Constance.

Polar organic micropollutants (MPs) can have ecotoxicological effects on aquatic ecosystems and their occurrence in drinking water is a threat to public health. An extensive exposure assessment of MPs in large river and lake catchments is a necessary but challenging proposition for researchers and regulators. To get a complete picture of MP exposure in a large catchment, we employed a novel integrated strategy including MP measurement in the international catchment of Lake Constance and mass-flux modeling. A comprehensive screening of 252 MPs in the lake water by high-resolution mass spectrometry was used to identify the most commonly present MPs for the study site. It was found that the wastewater borne MPs diclofenac, carbamazepine, sulfamethoxazole, acesulfame, sucralose, benzotriazole, and methylbenzotriazole accounted for the most frequent and prominent findings. The concentration pattern of these compounds in the catchment was calculated based on regionalized inputs from wastewater treatment plants (WWTPs) and substance specific elimination rates. In 52, 8, and 3 of the 112 investigated river locations the concentration exceeded the predicted no-effect levels for diclofenac, sulfamethoxazole and carbamazepine, respectively. By coupling the catchment and lake model the effect of future trends in usage as well as possible mitigation options were evaluated for the tributaries and the lake. The upgrade of the major WWTPs in the catchment with a postozonation step would lead to a load reduction between 32% and 52% for all substances except for sucralose (10%).

Induction of bona fide regulatory T cells after liver transplantation - the potential influence of polyclonal antithymocyte globulin.

T-cell-depleting strategies are an integral part of immunosuppressive regimens used in the hematological and solid organ transplant setting. Besides prevention of alloreactivity, treatment with rabbit antithymocyte globulin (rATG) has been related to the induction of immunoregulatory T cells (Treg) in vitro and in vivo. To investigate Treg induced by rATG, we prospectively studied the effect of rATG induction therapy in liver-transplanted recipients in vivo (n = 28). Treg induction was further evaluated by means of Treg-specific demethylation region (TSDR) analysis within the FOXP3 locus. Whereas no induction of CD4(+) CD25(high) CD127(-) Treg could be observed by phenotypic analysis, we could demonstrate an induction of TSDR(+) T cells within CD4(+) T cells exclusively for rATG-treated patients in the long-term (day 540) compared with controls (P = NS). Moreover, although in vitro experiments confirm that rATG primarily led to a conversion of CD4(+) CD25(-) into CD4(+) CD25(+) T cells displaying immunosuppressive capacities, these cells cannot be classified as bona fide Treg based on their FOXP3 demethylation pattern. Consequently, the generation of Treg after rATG co-incubation in vitro does not reflect the mechanisms of Treg induction in vivo and therefore the potential clinical relevance of these cells for transplant outcome remains to be determined.

Photoluminescence of uranium(VI): quenching mechanism and role of uranium(V).

The photoluminescence of uranium(VI) is observed typically in the wavelength range 400-650 nm with the lifetime of several hundreds mus and is known to be quenched in the presence of various halide ions (case A) or alcohols (case B). Here, we show by density functional theory (DFT) calculations that the quenching involves an intermediate triplet excited state that exhibits uranium(V) character. The DFT results are consistent with previous experimental findings suggesting the presence of photoexcited uranium(V) radical pair during the quenching process. In the ground state of uranyl(VI) halides, the ligand contributions to the highest occupied molecular orbitals increase with the atomic number (Z) of halide ion allowing larger ligand-to-metal charge transfer (LMCT) between uranium and the halide ion. Consequently, a larger quenching effect is expected as Z increases. The quenching mechanism is essentially the same in cases A and B, and is driven by an electron transfer from the quencher to the UO(2)(2+) entity. The relative energetic stabilities of the triplet excited state define the "fate" of uranium, so that in case A uranium(V) is oxidized back to uranium(VI), while in case B uranium remains as pentavalent.

Targeting aquatic microcontaminants for monitoring: exposure categorization and application to the Swiss situation.

BACKGROUND, AIM, AND SCOPE: Aquatic microcontaminants (MCs) comprise diverse chemical classes, such as pesticides, biocides, pharmaceuticals, consumer products, and industrial chemicals. For water pollution control and the evaluation of water protection measures, it is crucial to screen for MCs. However, the selection and prioritization of which MCs to screen for is rather difficult and complex. Existing methods usually are strongly limited because of a lack of screening regulations or unavailability of required data. METHOD AND MODELS: Here, we present a simple exposure-based methodology that provides a systematic overview of a broad range of MCs according to their potential to occur in the water phase of surface waters. The method requires input of publicly available data only. Missing data are estimated with quantitative structure-property relationships. The presented substance categorization methodology is based on the chemicals' distribution behavior between different environmental media, degradation data, and input dynamics. RESULTS: Seven different exposure categories are distinguished based on different compound properties and input dynamics. Ranking the defined exposure categories based on a chemical's potential to occur in the water phase of surface waters, exposure categories I and II contain chemicals with a very high potential, categories III and IV contain chemicals with a high potential, and categories V and VI contain chemicals with a moderate to low potential. Chemicals in category VII are not evaluated because of a lack of data. We illustrate and evaluate the methodology on the example of MCs in Swiss surface waters. Furthermore, a categorized list containing potentially water-relevant chemicals is provided. DISCUSSION: Chemicals of categories I and III continuously enter surface waters and are thus likely to show relatively steady concentrations. Therefore, they are best suited for water monitoring programs requiring a relatively low sampling effort. Chemicals in categories II and IV have complex input dynamics. They are consequently more difficult to monitor. However, they should be considered if an overall picture is needed that includes contaminants from diffuse sources. CONCLUSIONS: The presented methodology supports compound selection for (a) water quality guidance, (b) monitoring programs, and (c) further research on the chemical's ecotoxicology. The results from the developed categorization procedure are supported by data on consumption and observed concentrations in Swiss surface waters. The presented methodology is a tool to preselect potential hazardous substances based on exposure-based criteria for policy guidance and monitoring programs and a first important step for a detailed risk assessment for potential microcontaminants.

Dependence of persistence and long-range transport potential on gas-particle partitioning in multimedia models.

A novel approach of modeling gas-particle partitioning using polyparameter linear free energy relationships (ppLFERs) is implemented into three different multimedia box models (the OECD Pov and LRTP screening tool (The Tool), ChemRange, and CliMoChem) and compared to approaches based on the octanol-air partition coefficient (K(OA)). In all three multimedia models, calculated overall persistence is not strongly influenced (differences < 3%) by the gas-particle partitioning approach selected. The long-range transport potential (LRTP) is more sensitive to the choice of the gas-particle partitioning model. In CliMoChem, the LRTP of polar chemicals is higher if the ppLFER gas-particle partitioning approach is applied, with differences up to a factor of 2. Modeled concentrations of polar chemicals in Arctic air are also higher in the ppLFER version of CliMoChem. The model results obtained with the ppLFER approach are in good agreement with measured concentrations of alpha-HCH, methoxychlor, and trifluralin in Arctic air, whereas results from the K(OA)-based version of the model are in some cases lower by a factor of 10-100. If the required chemical property data are available, the ppLFER approach holds considerable potential to improve the gas-particle partitioning description for polar chemicals in multimedia models.

Alternative approaches for modeling gas-particle partitioning of semivolatile organic chemicals: model development and comparison.

We present a novel model of gas-particle partitioning based on polyparameter linear free energy relationships (ppLFERs) that is capable of representing a broad range of aerosol properties. We apply the model to semivolatile organic chemicals including PCBs, DDT, and polar pesticides, and compare it to a widely adopted model based on the octanol-air partition coefficient (K(OA)). For nonpolar chemicals and cases where sorption to aerosols is dominated by absorption into organic matter, the two models are highly correlated and both are appropriate. Significant differences between the models are found for (a) polar chemicals and (b) aerosols with low organic matter content. The explicit description of polar interactions in the ppLFER approach implies stronger interactions between chemicals and aerosols than the K(OA)-based model, which describes polar interactions only implicitly and to a limited extent. Practical application of the ppLFER-based model to a wide range of chemicals is currently limited by data gaps in measured Abraham solvation parameters and uncertainties in estimation methods.

Quantification of the new triketone herbicides, sulcotrione and mesotrione, and other important herbicides and metabolites, at the ng/l level in surface waters using liquid chromatography-tandem mass spectrometry.

The LC/ESI/MSMS method allows the trace quantification (ng/l) of the new triketone herbicides, i.e. sulcotrione and mesotrione, and important herbicides and metabolites, in natural waters. Solid phase extraction (SPE) for sample enrichment is performed with OASIS (recoveries 94-112% for parent herbicides). Neutral and acidic compounds were analyzed separately with ESI in positive and negative mode, respectively. Quantification limits varied between 0.5 and 10 ng/l. The acidic herbicides detection was improved by a neutralizing post-column addition solution. The influence of ion suppression on quantification is discussed in detail. It is shown that we could overcome this problem and achieve reliable quantification using isotope labeled internal standards (ILIS) for every single analyte. The methods performance is illustrated with samples from a lake depth profile.