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Hybridized plexcitonic states have unique properties which have been widely studied in recent decades in many research fields targeted at both fundamental science and innovative applications. However, to make these applications come true one needs to ensure the stabilization and preservation of electronic states and optical transitions in hybrid nanostructures, especially under the influence of external stressors, in regimes, that have not yet been comprehensively investigated. The present work shows that the nanohybrid system, composed of plasmonic nanoparticles and J-aggregates of organic molecules, displays outstanding resistance to harsh environmental stressors such as temperature, pH and strong light irradiation as well as demonstrates long-term stability and processability of the nanostructures both in weak and strong coupling regimes. These findings contribute to a deeper understanding of the physicochemical properties of plexcitonic nanoparticles and may find important implications for the development of potential applications in optoelectronics, optical imaging and chemo-bio-sensing and, in general, in the field of optical materials science., Authors acknowledge the financial support from the Ministry of Education and Science of the Russian Federation (grant no. 14.Y26.31.0011). Y. R. acknowledges the support from the Basque Government (grant no. IT1164-19). M. G. acknowledges support from the Basque Government (PIBA 2018-34), and Diputación Foral de Guipúzcoa (RED 2018, RED 2019). A. S. I. acknowledges the Maria de Maeztu Units of Excellence Programme – Grant No. MDM-2017-0720 Ministry of Science, Innovation and Universities.

Kohortenstudien sind prospektive Beobachtungsstudien. Sie sind in der Epidemiologie zum Studium von Krankheitsverlaufen und Risikofaktoren fest etabliert. Hinsichtlich der Beschreibung und Bewertung von Qualitatsmerkmalen epidemiologischer Kohortenstudien existieren jedoch keine Standards. Im TMF(Technologie- und Methodenplattform fur die vernetzte medizinische Forschung e. V.)-Projekt „Qualitatsmanagementstandards in Kohortenstudien“ sollte unter Beteiligung von Vertretern epidemiologischer Kohortenstudien ein Anforderungskatalog fur Qualitatsmerkmale der Studienvorbereitung und Studiendurchfuhrung zusammengestellt und bewertet werden. Der Anforderungskatalog wurde auf Basis eines Konsensprozesses von Vertretern aus sieben deutschen epidemiologischen Kohortenstudien erstellt. Um die Struktur und Elemente einer Anforderungsliste zu definieren, fanden Expertentreffen statt. In drei Bewertungswellen wurden Wichtigkeit und Implementierungsgrad aller Anforderungen bewertet. Konsentiert wurde ein Anforderungskatalog mit 138 Anforderungen, die in 10 Bereiche gegliedert sind: 1. Studiendokumente, 2. Instrumentenauswahl, 3. Untersuchungsplanung, 4. Organisationsstruktur, 5. Qualifizierung und Zertifizierung, 6. Probandenrekrutierung, 7. Untersuchungsvorbereitung und -durchfuhrung, 8. Logistik und Instandhaltung, 9. Datenerfassung und Datenmanagement sowie 10. Reporting und Monitoring. Insgesamt 41 Anforderungen wurden als essenziell, 91 als wichtig und 6 als weniger wichtig bewertet. Der Anforderungskatalog liefert Kohortenstudien Orientierungspunkte bei der Konzeption und Umsetzung, um eine moglichst hohe Struktur‑, Prozess- und Ergebnisqualitat zu erzielen. Die Bewertung der Wichtigkeit und des Implementationsgrades einzelner Anforderungen hangt vom Studiendesign ab. Die Ergebnisse konnen mit Anpassungen auch fur andere Studientypen relevant sein.

An understanding of the mechanisms of energy transfer and conversion on the nanoscale is one of the key requirements for an implementation of highly efficient photonic nanodevices based on hybrid organic/inorganic nanomaterials. In this work we conduct steady-state and time resolved optical studies of the emission properties of an ensembles and single semiconductor quantum dots and attached organic dye molecules. We revealed that the luminescence intensity of a hybrid structure does not follow the blinking behavior of quantum dots. We also demonstrated an efficient single photon generation from single hybrid nanostructures which involves an energy transfer from donor to acceptor as main excitation source., This work was supported by the Ministry of Education and Science of the Russian Federation under grant no. 14.Y26.31.0011. Y. R. and T. H. acknowledges support from Project Fis2016.80174-P (PLASMOQUANTA) from MINECO (Ministerio de Economiá y Competitividad), Spain.

Cohort studies are a longitudinal observational study type. They are firmly established within epidemiology to assess the course of diseases and risk factors. Yet, standards to describe and evaluate quality characteristics of cohort studies need further development.Within the TMF ("Technologie- und Methodenplattform für die vernetzte medizinische Forschung e. V.") project "Quality management standards in cohort studies", a catalogue of requirements was compiled and evaluated, focusing on the preparation and conduct of epidemiologic cohort studies.The catalogue of requirements was established based on a consensus process between representatives of seven German epidemiologic cohort studies. For this purpose, a set of expert meetings (telephone, face-to-face, web-based) was conducted and the importance of each element of the catalogue was assessed as well as its implementation.A catalogue of requirements with 138 requirements was consented. It is structured into ten sections: 1. Study documentation; 2. Selection of instruments; 3. Study implementation, 4. Organizational structure; 5. Qualification and certification; 6. Participant recruitment; 7. Preparation, conduct and follow-up processing of examinations; 8. Study logistics and maintenance, 9. Data capture and data management; 10. Reporting and monitoring. In total, 41 elements were categorized as being essential, 91 as important, and 6 as less important.The catalogue of requirements provides a guideline to improve the preparation and operation of cohort studies. The evaluation of the importance and degree of implementation of requirements depended on the study design. With adaptations, the catalogue might be transferable to other study types.

Mixed aerogels from semiconductor and metal nanoparticles represent an outstanding hybrid material with exceptional properties due to two striking advantages: the creation of a huge quantity of semiconductor-metal interfaces combined with a highly porous three-dimensional nanostructured network. We present a versatile synthetic pathway towards hybrid aerogels built up by joint gelation of CdTe and noble metal nanoparticles (Au, Pd and bimetallic Au/Pd). A straightforward HO treatment inducing gel formation is developed as a more elegant alternative compared to the established photooxidation approach. The use of HO allows a reproducible, simple and mild gel formation which can be easily upscaled. The tremendous influence of the HO concentration on gelation mechanism and gelation kinetics is revealed by photoluminescence quantum yield (PLQY) determinations. Resulting gels are extensively characterized via transmission electron microscopy (TEM), scanning TEM (STEM), energy dispersive X-ray analysis (EDX) as well as photoluminescence (PL) spectroscopy and PL lifetime measurements. By varying the composition of the herein presented noble metal nanoparticles in a controlled fashion the range of semiconductor-metal hybrid aerogels is widened, which demonstrates the versatility and consistency of our approach. This synthetic flexibility grants access to a variety of different mixed hybrid aerogels which are of high significance for catalytic, sensing and photonic applications., Parts of TEM investigations have been carried out at the Leibniz-Institut für Polymerforschung Dresden e.V. Access to their TEM facility is gratefully acknowledged. AD thanks the Government of the Russian Federation (Grant 074-U01) through ITMO Post-Doctoral Fellowship.

Mixed metal–semiconductor nanocrystal aerogels are fabricated, which are light-emitting and highly porous macroscopic monoliths. Thiol-stabilized CdTe and Au nanoparticles from aqueous synthesis act as building blocks for the hybrid material. The Au colloids undergo a surface-modifi cation to enhance the particle stability and achieve thiol functionalities. A photochemical treatment is applied for the gelation process which is found to be reversible by subsequent addition of thiol molecules. Via supercritical drying aerogels are formed. The variation of the initial CdTe to Au nanoparticle ratio permits a facile tuning of the content and the properties of the resulting aerogels. The obtained structures were characterized by means of optical spectroscopy, electron microscopy, elemental analysis, and nitrogen physisorption.

The MRI study within the German National Cohort, a large-scale, population-based, longitudinal study in Germany, comprises comprehensive characterization and phenotyping of a total of 30 000 participants using 3-Tesla whole-body MR imaging. A multi-centric study design was established together with dedicated core facilities for e. g. managing incidental findings or providing quality assurance. As such, the study represents a unique opportunity to substantially impact imaging-based risk stratification leading to personalized and precision medicine. Supported by the developments in the field of computational science, the newly developing scientific field of radiomics has large potential for the future. In the present article we provide an overview on population-based imaging and Radiomics and conceptualize the rationale and design of the MRI study within the German National Cohort. Key Points: • Population-based imaging and Radiomics constitute two emerging fields with great oppertunities and challenges for Radiology. • As part of the MRI-study of the NAKO approximately 30 000 subjects will undergo 3 Tesla whole-body MRI. • MR Imaging data is publicly accessable and will provide important insights into the natural history of disease processes and personalized risk profiles of the general population. Citation Format: • Schlett CL, Hendel T, Weckbach S et al. Population-Based Imaging and Radiomics: Rationale and Perspective of the German National Cohort MRI Study. Fortschr Rontgenstr 2016; 188: 652 – 661

INTRODUCTION: Whole-body magnetic resonance (MR) imaging is increasingly implemented in population-based cohorts and clinical settings. However, to quantify the variability introduced by the different scanners is essential to make conclusions about clinical and biological data, and relevant for internal/external validity. Thus, we determined the interscanner and intrascanner variability of different 3 T MR scanners for whole-body imaging. METHODS: Thirty volunteers were enrolled to undergo multicentric, interscanner as well intrascanner imaging as part of the German National Cohort pilot studies. A comprehensive whole-body MR protocol was installed at 9 sites including 7 different MR scanner models by all 4 major vendors. A set of quantitative, organ-specific measures (n = 20; eg, volume of brain's gray/white matter, pulmonary trunk diameter, vertebral body height) were obtained in blinded fashion. Reproducibility was determined using mean weighted relative differences and intraclass correlation coefficients. RESULTS: All participants (44 +/- 14 years, 50% female) successfully completed the imaging protocol except for two because of technical issues. Mean scan time was 2 hours and 32 minutes and differed significantly across scanners (range, 1 hour 59 minutes to 3 hours 12 minutes). A higher reproducibility of obtained measurements was observed for intrascanner than for interscanner comparisons (intraclass correlation coefficients, 0.80 +/- 0.17 vs 0.60 +/- 0.31, P = 0.005, respectively). In the interscanner comparison, mean relative difference ranged from 1.0% to 53.2%. Conversely, in the intrascanner comparison, mean relative difference ranged from 0.1% to 15.6%. There were no statistical differences for intrascanner and interscanner reproducibility between the different organ foci (all P >/= 0.24). CONCLUSIONS: While whole-body MR imaging-derived, organ-specific parameters are generally associated with good to excellent reproducibility, smaller differences are obtained when using identical MR scanner models by a single vendor.

Neurons in the nervous system can change their functional properties over time. At present, there are no techniques that allow reliable monitoring of changes within identified neurons over repeated experimental sessions. We increased the signal strength of troponin C-based calcium biosensors in the low-calcium regime by mutagenesis and domain rearrangement within the troponin C calcium binding moiety to generate the indicator TN-XXL. Using in vivo two-photon ratiometric imaging, we show that TN-XXL exhibits enhanced fluorescence changes in neurons of flies and mice. TN-XXL could be used to obtain tuning curves of orientation-selective neurons in mouse visual cortex measured repeatedly over days and weeks. Thus, the genetically encoded calcium indicator TN-XXL allows repeated imaging of response properties from individual, identified neurons in vivo, which will be crucial for gaining new insights into cellular mechanisms of plasticity, regeneration and disease.

Zusammenfassung Die Steuerung des Verhaltens ist die biologische Funktion des Gehirns und der zentrale Gegenstand der Neurowissenschaft. Um diese Frage anzugehen, stellen wir ein zellulär sehr einfaches Modellsystem vor. Das Riechsystem der Taufliegenlarve (Drosophila) ist grundsätzlich dem der erwachsenen Fliege und dem von Säugern sehr ähnlich, sowohl was die „Logik“ der Rezeptorgenexpression angeht, als auch bezüglich der neuronalen Verschaltungen im Gehirn. Dabei kommen die Larven mit millionenfach weniger Zellen aus und können sich trotzdem in ihrer Duftumwelt zurecht finden und einfache Duftlernaufgaben bewältigen. Wir geben eine Übersicht über die Riech- und Schmecksysteme der Drosophila-Larve und stellen ein robustes Experiment zum verknüpfenden, assoziativen Lernen zwischen Düften und Futterbelohnung vor. Dazu werden erste Erkenntnisse über die beteiligten molekularen Vorgänge, Gehirnbereiche und Zellen dargestellt. Die Kombination aus Lernfähigkeit und zellulärer Einfachkeit der Larve mit den reichhaltigen Methoden der Drosophila-Genetik bereichern die neurobiologische Forschung um ein vielversprechendes Modellsystem.

To identify and establish novel imaging-based biomarkers of risk, the German National Cohort MR imaging study is designed as a prospective cohort study that will enroll 30 000 participants and will apply a highly standardized study set with respect to technical equipment, quality management, and algorithms for the management of incidental findings. Purpose To detail the rationale, design, and future perspective of implementing whole-body magnetic resonance (MR) imaging in the German National Cohort, a large multicentric population-based study. Materials and Methods All institutional review boards approved the study, and informed consent is obtained before study enrollment. Participants are enrolled from a random sample of the general population at five dedicated imaging sites among 18 recruitment centers. MR imaging facilities are equipped with identical 3.0-T imager technology and use uniform MR protocols. Imager-specific hardware and software settings remained constant over the study period. On-site and centralized measures of image quality enable monitoring of completeness of the acquisitions and quality of each of the MR sequences. Certified radiologists read all MR imaging studies for presence of incidental findings according to predefined algorithms. Results Over a 4-year period, six participants per day are examined at each center, totaling a final imaging cohort of approximately 30 000 participants. The MR imaging protocol is identical for each site and comprises a set of 12 native series to cover neurologic, cardiovascular, thoracoabdominal, and musculoskeletal imaging phenotypes totaling approximately 1 hour of imaging time. A dedicated analysis platform as part of a central imaging core incorporates a thin client-based integrative and modular data handling platform to enable multicentric off-site image reading for incidental findings. Scientific analysis will be pursued on a per-project hypothesis-driven basis. Conclusion Population-based whole-body MR imaging as part of the German National Cohort will serve to compile a comprehensive image repository, will provide insight into physiologic variants and subclinical disease burden, and has the potential to enable identification of novel imaging biomarkers of risk.

This paper studies the UV–vis absorbance of colloidal gold nanoparticles at 400 nm and validates it as a method to determine Au(0) concentrations in colloidal gold solutions. The method is shown to be valid with restrictions depending on the investigated system. The uncertainty of the determined Au(0) concentration can be up to 30%. This deviation is the result of the combined influence of parameters such as particle size, surface modification, or oxidation state. However, quantifying the influence of these parameters enables a much more precise Au(0) determination for specific systems. As an example, the reduction process of the well-known Turkevich method was monitored and the Au(0) concentration was determined with a deviation of less than 5%. Hence, a simple, fast, easy, and cheap in situ method for Au(0) determination is demonstrated that has in the presence of other gold species such as Au(III) an unprecedented accuracy.

Recent advance in the design of genetically encoded calcium indicators (GECIs) has further increased their potential for direct measurements of activity in intact neural circuits. However, a quantitative analysis of their fluorescence changes (ΔF)in vivoand the relationship to the underlying neural activity and changes in intracellular calcium concentration (Δ[Ca2+]i) has not been given. We used two-photon microscopy, microinjection of synthetic Ca2+dyes andin vivocalibration of Oregon-Green-BAPTA-1 (OGB-1) to estimate [Ca2+]iat rest and Δ[Ca2+]iat different action potential frequencies in presynaptic motoneuron boutons of transgenicDrosophilalarvae. We calibrated ΔFof eight different GECIsin vivoto neural activity, Δ[Ca2+]i, and ΔFof purified GECI protein at similar Δ[Ca2+]in vitro. Yellow Cameleon 3.60 (YC3.60), YC2.60, D3cpv, and TN-XL exhibited twofold higher maximum ΔFcompared with YC3.3 and TN-L15in vivo. Maximum ΔFof GCaMP2 and GCaMP1.6 were almost identical. Small Δ[Ca2+]iwere reported best by YC3.60, D3cpv, and YC2.60. The kinetics of Δ[Ca2+]iwas massively distorted by all GECIs, with YC2.60 showing the slowest kinetics, whereas TN-XL exhibited the fastest decay. Single spikes were only reported by OGB-1; all GECIs were blind for Δ[Ca2+]iassociated with single action potentials. YC3.60 and D3cpv tentatively reported spike doublets.In vivo, theKD(dissociation constant) of all GECIs was shifted toward lower values, the Hill coefficient was changed, and the maximum ΔFwas reduced. The latter could be attributed to resting [Ca2+]iand the optical filters of the equipment. These results suggest increased sensitivity of new GECIs but still slow on rates for calcium binding.

Why does Pavlov's dog salivate? In response to the tone, or in expectation of food? While in vertebrates behaviour can be driven by expected outcomes, it is unknown whether this is true for non-vertebrates as well. We find that, in the Drosophila larva, odour memories are expressed behaviourally only if animals can expect a positive outcome from doing so. The expected outcome of tracking down an odour is determined by comparing the value of the current situation with the value of the memory for that odour. Memory is expressed behaviourally only if the expected outcome is positive. This uncovers a hitherto unrecognized evaluative processing step between an activated memory trace and behaviour control, and argues that learned behaviour reflects the pursuit of its expected outcome. Shown in a system with a simple brain, an apparently cognitive process like representing the expected outcome of behaviour seems to be a basic feature of behaviour control.

Summary During classical conditioning, a positive or negative value is assigned to a previously neutral stimulus, thereby changing its significance for behavior. If an odor is associated with a negative stimulus, it can become repulsive. Conversely, an odor associated with a reward can become attractive. By using Drosophila larvae as a model system with minimal brain complexity, we address the question of which neurons attribute these values to odor stimuli. In insects, dopaminergic neurons are required for aversive learning, whereas octopaminergic neurons are necessary and sufficient for appetitive learning [1–4]. However, it remains unclear whether two independent neuronal populations are sufficient to mediate such antagonistic values. We report the use of transgenically expressed channelrhodopsin-2 [5], a light-activated cation channel, as a tool for optophysiological stimulation of genetically defined neuronal populations in Drosophila larvae. We demonstrate that distinct neuronal populations can be activated simply by illuminating the animals with blue light. Light-induced activation of dopaminergic neurons paired with an odor stimulus induces aversive memory formation, whereas activation of octopaminergic/tyraminergic neurons induces appetitive memory formation. These findings demonstrate that antagonistic modulatory subsystems are sufficient to substitute for aversive and appetitive reinforcement during classical conditioning.

We investigate the organization of behaviour across sensory modalities, using larval Drosophila melanogaster. We ask whether olfactory learning and behaviour are affected by visual processing. We find that: (1) Visual choice does not affect concomitant odour choice. (2) Visual context does not influence odour learning, nor do changes of visual context between training and test affect retrieval of odour memory. (3) Larvae cannot solve a biconditional discrimination task, despite generally permissive conditions. In this task, larvae are required to establish conditional associations: in light, one odour is rewarded and the other one is not, whereas in dark the opposite contingency is established. After such training, choice between the two odours is equal under light and dark testing conditions, suggesting that larvae do not establish odour memories specifically for one visual context only. Together, these data suggest that, in larval Drosophila, olfactory learning and behaviour are ‘insulated’ against visual processing.

The ability to learn is universal among animals; we investigate associative learning between odors and “tastants” in larval Drosophila melanogaster. As biologically important gustatory stimuli, like sugars, salts, or bitter substances have many behavioral functions, we investigate not only their reinforcing function, but also their response-modulating and response-releasing function. Concerning the response-releasing function, larvae are attracted by fructose and repelled by sodium chloride and quinine; also, fructose increases, but salt and quinine suppress feeding. However, none of these stimuli has a nonassociative, modulatory effect on olfactory choice behavior. Finally, only fructose but neither salt nor quinine has a reinforcing effect in associative olfactory learning. This implies that the response-releasing, response-modulating and reinforcing functions of these tastants are dissociated on the behavioral level. These results open the door to analyze how this dissociation is brought about on the cellular and molecular level; this should be facilitated by the cellular simplicity and genetic accessibility of the Drosophila larva.

SUMMARYAn understanding of associative learning is facilitated if it can be analyzed in a simple animal like the fruit fly Drosophila. Here, we introduce the first visual associative learning paradigm for larval Drosophila; this is remarkable as larvae have an order of magnitude fewer neurons than adult flies. Larvae were subjected to either of two reciprocal training regimes: Light+/Dark- or Light-/Dark+. Subsequently, all larvae were individually tested for their preference between Light versus Dark. The difference between training regimes was therefore exclusively which visual situation was associated with which reinforcer;differences observed during the test thus reflected exclusively associative learning. For positive reinforcement (+) we used fructose (FRU), and for negative reinforcement (-) either quinine or sodium chloride (QUI, NaCl). Under these conditions, associative learning could be reproducibly observed in both wild-type strains tested. We then compared the effectiveness of training using differential conditioning, with both positive and negative reinforcement, to that using only positive or only negative reinforcement. We found that FRU only, but neither QUI nor NaCl, was in itself effective as a reinforcer. This is the first demonstration of appetitive learning in larval Drosophila. It is now possible to investigate the behavioral and neuronal organization of appetitive visual learning in this simple and genetically easy-to-manipulate experimental system.