Intriguing Heteroleptic ZnII^{II} bis(dipyrrinato) Emitters in the Far-Red Region With Large Pseudo-Stokes Shift for Bioimaging

Novel heteroleptic ZnII bis(dipyrrinato) complexes were prepared as intriguing emitters. With our tailor-made design, we achieved far-red emissive complexes with a photoluminescence quantum yield up to 45% in dimethylsulfoxide and 70% in toluene. This means that heteroleptic Zn$^{II}$ bis(dipyrrinato) complexes retain very intense emission also in polar solvents, in contrast to their homoleptic counterparts, which we prepared for comparing the photophysical properties. It is evident from the absorption and excitation spectra that heteroleptic complexes present the characteristic features of both ligands: the plain dipyrrin (L$_{p}$) and the π-extended dipyrrin (L$_{π}$). On the contrary, the emission comes exclusively from the π-extended dipyrrin L$_{π}$, suggesting an interligand nonradiative transition that causes a large pseudo-Stokes shift (up to 4,600 cm$_{-1}$). The large pseudo-Stokes shifts and the emissive spectral region of these novel heteroleptic Zn$^{II}$ bis(dipyrrinato) complexes are of great interest for bioimaging applications. Thus, their high biocompatibiliy with four different cell lines make them appealing as new fluorophores for cell imaging

Digitally supported learning in nursing training: The Care Reflection Online (CARO) learning environment

Die tiefgreifende Mediatisierung (Hepp 2018) schliesst nahezu alle gesellschaftlichen Bereiche ein, so auch das Gesundheitswesen. In der Pflegeausbildung ist das Potential des Einsatzes digitaler Medien noch nicht vollumfänglich ausgeschöpft. Zwar werden punktuell digitale Medien, wie etwa Lernplattformen (Moodle), Programme (PowerPoint) oder einzelne Methoden (flinga) in die Lehre integriert. Dennoch erfolgt der Einsatz selten pflegedidaktisch fundiert (Darmann-Finck 2010). Mediendidaktische Ansätze, anhand derer das digital unterstütze Lernen gestaltet werden kann (Kerres 2018; Jahnke 2015), adressieren die Anforderungen des Unterrichtsgegenstandes «Pflege» nicht ausreichend. Im Projekt CARO (Laufzeit 2016 bis 2019) wurde daher ein sog. Classroom-Learning-Interaction-System (CARO CLIS) zur Unterstützung von Live-Interaktionen im Klassenraum entwickelt und evaluiert. Das CARO CLIS unterstützt komplexe Lern-, Interaktions- und Reflexionsprozesse pflege- und mediendidaktisch fundiert. Im folgenden Beitrag wird sowohl die Entwicklung und Evaluation der Software als auch der Unterrichtsinhalte auf Basis des Design-based Research Ansatzes (Koppel 2016) aufgezeigt. Darüber hinaus wird exemplarisch dargestellt, wie mit dem CARO CLIS pflegedidaktisch fundierte komplexe Bildungsziele mit Hilfe mediendidaktischer Interaktionsformate im Unterricht umgesetzt werden können.The deep mediatization (Hepp 2018) integrates almost all sectors of society, including health care. In nursing training, the potential of the use of digital media has not yet been fully exploited. Digital media, such as learning platforms (Moodle), programs (PowerPoint) or individual tools (flinga), are integrated in teaching processes. Nevertheless, the use is rarely carried out in a nursing-didactically way (Darmann-Finck 2010). Media didactic approaches to shape digitally supported learning (Kerres 2018; Jahnke 2015), do not adequately address the requirements of contents in nursing training. In the CARO project (running 2016 to 2019), a so-called Classroom Learning Interaction System (CARO CLIS) was developed and evaluated to support live interactions in the classroom. The CARO CLIS supports complex learning, interaction and reflection processes in a nursing and media-didactic way. The following article shows the development and evaluation of the software as well as the teaching content based on the design-based research approach (DBR) (Koppel 2016). In addition, it is exemplified how the CARO CLIS supports nursing-didactically well-founded complex educational goals using media-didactic interaction formats

On the Relation between a Nonlinear Elliptic Equation and Its Uniform Approximation

AbstractThe qualitative behavior of the solution set of nonlinear elliptic boundary value problems has in some instances been studied by reducing the partial differential equation to a related algebraic equation. Although this procedure often gives a good picture of the bifurcation diagram, it can be quite wrong. In this paper some relationships between the solutions of the two problems are investigated

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Molecular dynamics simulations of sorption and diffusion processes in pervaporation membranes

Ziel dieser Theorie-betonten Arbeit war es, durch die Anwendung von "Molecular Modelling"-Techniken einen Beitrag zur Aufklärung von Transportvorgängen in Pervaporationsmembranen zu leisten. Mittels molekulardynamischer (MD) Simulationen wurden 21 Grenzflächenmodelle von modifizierten glasartigen Polymethacrylaten und gummiartigen Polysiloxanen in Kontakt mit dem vorgegebenen Benzol/n-Heptan-Feedgemisch (20:80 Gew.-%) untersucht. Um die Simulationsmodelle quantitativ erfassen zu können, wurden spezielle Programme zur Auswertung entwickelt. Zunächst war die Frage zu klären, ob die Stofftrennung der großen Permeanden Benzol und n-Heptan mit MD-Methoden überhaupt sinnvoll untersucht werden kann. Im Rahmen der in dieser Arbeit durchgeführten MD-Simulationen konnte z.B. in guter Übereinstimmung mit Experimenten das erwartete, nicht-selektive Verhalten von Polydimethylsiloxanmembranen und die ausgeprägte Benzoladsorption an Polymethylmethacrylatoberflächen beobachtet werden. Durch den Vergleich der in dieser Arbeit erzielten Ergebnisse mit den verfügbaren experimentellen Daten konnte damit erstmalig nachgewiesen werden, daß sich MD-Methoden prinzipiell auch zur Vorhersage von Trenneffekten in der organophilen Pervaporation eignen. Ein weiteres Ziel dieser Untersuchungen war es, experimentell angewendete Strategien zur Verbesserung der Trennleistung von Polymethacrylaten bezüglich der genannten Feedlösung mit MD-Methoden zu überprüfen. Dabei haben sich für die Erhöhung der Benzolaffinität bei den untersuchten Modellpolymeren neben einem möglichst hohen Freien Volumen die Einführung von Benzyl- und Carboxylgruppen als vorteilhaft erwiesen. Anhand der Simulationen konnte aber auch festgestellt werden, daß Modifikationen von Modellpolymeren mit benzylischen Gruppen in Kombination mit einer ungünstigen Verteilung des Freien Volumens voraussichtlich eher geringe Permeabilitäten für Benzol und n-Heptan erwarten lassen. Anhand der MD-Simulationen von Polymer/Feed-Systemen konnten zumeist schneller Trendaussagen zur Benzol/n-Heptan-Trennung formuliert werden als mit Referenzmessungen möglich gewesen wäre, da sich der experimentelle Aufwand zur Herstellung der hier simulierten Polymermembranen als wesentlich größer als erwartet herausstellte. Somit konnten mit den hier durchgeführten MD-Simulationen einerseits Vorschläge für möglicherweise geeignete Modifikationen in die Synthesevorhaben eingebracht werden, andererseits konnten Modifikationen verworfen werden, die sich in der Simulation als ungeeignet herausgestellt haben, wodurch der Syntheseaufwand in einigen Fällen reduziert werden konnte. In der Simulation konnte außerdem festgestellt werden, daß die Diffusion von Benzol- und n-Heptanmolekülen in glasigen Polymethacrylaten mit unterschiedlichen Mechanismen erfolgt. Aufgrund der Beobachtung, daß sich die konformationsflexiblen n-Heptanmoleküle offenbar den Diffusionskanälen in der Polymermatrix anpassen können, nutzen diese eine "schlängelnde" Bewegung zum Fortkommen. Dahingegen bevorzugen die starren Benzolmoleküle einen "Loch zu Loch"-Sprungmechanismus. In gummiartigen Polymeren wurde bei Benzolmolekülen ein kombinierter Mechanismus aus Sprüngen und zielgerichtetem Fortkommen gefunden

Panel 3: political consultancy: an area for information systems academicians to create value?

Information Systems are increasingly a topic of, and underlie, the implementation of most government policies. As such they would seem to provide an enormous opportunity for IS academicians to provide 'political consultancy' and to offer their expertise in relation to political decision making. Throughout Europe and around the world, issues such as data privacy, online gaming, the protection of youth, net neutrality, media competency, public health ICT, ICT-based citizen services, digital divide, encryption versus transparency, and the social, competitive, and political impacts of phenomena such as Google, Facebook, and Twitter are being considered by policy makers; and each of these requires careful understanding of information systems issues. However, the contributions of IS academicians to political decision making come across as minor compared to our colleagues in the fields of law, political science, or economics. In the panel, we will explore the pros and cons of senior and junior IS academicians getting involved in these activities from an individual's, a school's, and a community's perspective. Panelists will share their experiences with political consultancy and hope to intensively discuss with the audience, mainly along their interests, ideas, and counter-positions

TLR2 has a detrimental role in mouse transient focal cerebral ischemia

A significant up-regulation of Toll-like-receptor (TLR) mRNAs between 3 and 48 h reperfusion time after induction of transient focal cerebral ischemia for 1 h was revealed by applying global gene expression profiling in postischemic mouse brains. Compared to TLR4 and TLR9, TLR2 proved to be the most significantly up-regulated TLR in the ipsilateral brain hemisphere. TLR2-protein was found to be expressed mainly in microglia in the postischemic brain tissue, but also in selected endothelial cells, neurons, and astrocytes. Additionally, TLR2-related genes with pro-inflammatory and pro-apoptotic capabilities were induced. Therefore we hypothesized that TLR2-signaling could exacerbate the primary brain damage after ischemia. Two days after induction of transient focal cerebral ischemia (1 h), we found a significant decrease of the infarct volume in TLR2 deficient mice compared to wild type mice (75 ± 5 vs. 42 ± 7 mm3). We conclude that TLR2 up-regulation and TLR2-signaling are important events in focal cerebral ischemia and contribute to the deterioration of ischemic damage

A cyclic GMP signalling module that regulates gliding motility in a malaria parasite.

The ookinete is a motile stage in the malaria life cycle which forms in the mosquito blood meal from the zygote. Ookinetes use an acto-myosin motor to glide towards and penetrate the midgut wall to establish infection in the vector. The regulation of gliding motility is poorly understood. Through genetic interaction studies we here describe a signalling module that identifies guanosine 3', 5'-cyclic monophosphate (cGMP) as an important second messenger regulating ookinete differentiation and motility. In ookinetes lacking the cyclic nucleotide degrading phosphodiesterase delta (PDEdelta), unregulated signalling through cGMP results in rounding up of the normally banana-shaped cells. This phenotype is suppressed in a double mutant additionally lacking guanylyl cyclase beta (GCbeta), showing that in ookinetes GCbeta is an important source for cGMP, and that PDEdelta is the relevant cGMP degrading enzyme. Inhibition of the cGMP-dependent protein kinase, PKG, blocks gliding, whereas enhanced signalling through cGMP restores normal gliding speed in a mutant lacking calcium dependent protein kinase 3, suggesting at least a partial overlap between calcium and cGMP dependent pathways. These data demonstrate an important function for signalling through cGMP, and most likely PKG, in dynamically regulating ookinete gliding during the transmission of malaria to the mosquito

The urinary proteomics classifier chronic kidney disease 273 predicts cardiovascular outcome in patients with chronic kidney disease

Background: The urinary proteomic classifier chronic kidney disease 273 (CKD273) is predictive for the development and progression of chronic kidney disease (CKD) and/or albuminuria in type 2 diabetes. This study evaluates its role in the prediction of cardiovascular (CV) events in patients with CKD Stages G1-G5. Methods: We applied the CKD273 classifier in a cohort of 451 patients with CKD Stages G1-G5 followed prospectively for a median of 5.5 years. Primary endpoints were all-cause mortality, CV mortality and the composite of non-fatal and fatal CV events (CVEs). Results: In multivariate Cox regression models adjusting for age, sex, prevalent diabetes and CV history, the CKD273 classifier at baseline was significantly associated with total mortality and time to fatal or non-fatal CVE, but not CV mortality. Because of a significant interaction between CKD273 and CV history (P = 0.018) and CKD stages (P = 0.002), a stratified analysis was performed. In the fully adjusted models, CKD273 classifier was a strong and independent predictor of fatal or non-fatal CVE only in the subgroup of patients with CKD Stages G1-G3b and without a history of CV disease. In those patients, the highest tertile of CKD273 was associated with a >10-fold increased risk as compared with the lowest tertile. Conclusions: The urinary CKD273 classifier provides additional independent information regarding the CV risk in patients with early CKD stage and a blank CV history. Determination of CKD273 scores on a random urine sample may improve the efficacy of intensified surveillance and preventive strategies by selecting patients who potentially will benefit most from early risk management