Chiral plasmonics of self-assembled nanorod dimers

Chiral nanoscale photonic systems typically follow either tetrahedral or helical geometries that require four or more different constituent nanoparticles. Smaller number of particles and different chiral geometries taking advantage of the self-organization capabilities of nanomaterials will advance understanding of chiral plasmonic effects, facilitate development of their theory, and stimulate practical applications of chiroplasmonics. Here we show that gold nanorods self-assemble into side-by-side orientated pairs and ‘‘ladders’’ in which chiral properties originate from the small dihedral angle between them. Spontaneous twisting of one nanorod versus the other one breaks the centrosymmetric nature of the parallel assemblies. Two possible enantiomeric conformations with positive and negative dihedral angles were obtained with different assembly triggers. The chiral nature of the angled nanorod pairs was confirmed by 4p full space simulations and the first example of single-particle CD spectroscopy. Self-assembled nanorod pairs and ‘‘ladders’’ enable the development of chiral metamaterials, (bio)sensors, and new catalytic processes

Haploinsufficiency of NFKBIA reshapes the epigenome antipodal to the IDH mutation and imparts disease fate in diffuse gliomas

Genetic alterations help predict the clinical behavior of diffuse gliomas, but some variability remains uncorrelated. Here, we demonstrate that haploinsufficient deletions of chromatin-bound tumor suppressor NFKB inhibitor alpha (NFKBIA) display distinct patterns of occurrence in relation to other genetic markers and are disproportionately present at recurrence. NFKBIA haploinsufficiency is associated with unfavorable patient outcomes, independent of genetic and clinicopathologic predictors. NFKBIA deletions reshape the DNA and histone methylome antipodal to the IDH mutation and induce a transcriptome landscape partly reminiscent of H3K27M mutant pediatric gliomas. In IDH mutant gliomas, NFKBIA deletions are common in tumors with a clinical course similar to that of IDH wild-type tumors. An externally validated nomogram model for estimating individual patient survival in IDH mutant gliomas confirms that NFKBIA deletions predict comparatively brief survival. Thus, NFKBIA haploinsufficiency aligns with distinct epigenome changes, portends a poor prognosis, and should be incorporated into models predicting the disease fate of diffuse gliomas

DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith-Wiedemann syndrome

Tierling S, Souren NY, Reither S, Zang KD, Meng-Hentschel J, Leitner D, Oehl-Jaschkowitz B, Walter J. DNA methylation studies on imprinted loci in a male monozygotic twin pair discordant for Beckwith-Wiedemann syndrome. Beckwith-Wiedemann syndrome (BWS) is one of the most prevalent congenital disorders predominantly caused by epigenetic alterations. Here we present an extensive case study of a monozygotic monochorionic male twin pair discordant for BWS. Our analysis allows to correlate BWS symptoms, like a protruding tongue, indented ears and transient neonatal hypoglycaemia, to an abnormal methylation at the KvDMR1. DNAs extracted from peripheral blood, skin fibroblasts, saliva and buccal swab of both twins, their sister and parents were analysed at 11 differentially methylated regions (DMRs) including all four relevant DMRs of the BWS region. The KvDMR1 was exclusively found to be hypomethylated in all cell types of the affected BWS twin, while the unaffected twin and the relatives showed normal methylation in fibroblasts, buccal swab and saliva DNA. Interestingly, the twins share a common blood-specific hypomethylation phenotype most probably caused by a feto-fetal transfusion between both twins. Because microsatellite analysis furthermore revealed a normal biparental karyotype for chromosome 11, our results point to an exclusive correlation of the observed BWS symptoms to locally restricted epimutations at the KvDMR1 of the maternal chromosome

Zentrale Schritte der Erstellung, Durchführung, Auswertung und Qualitätssicherung des schriftlichen Teils der eidgenössischen Prüfung Humanmedizin (Schweizer Staatsexamen)

Purpose: This report describes the essential steps in the development, implementation, evaluation and quality assurance of the written part of the Swiss Federal Licensing Examination for Human Medicine (FLE) and the insights gained since its introduction in 2011.Methods: Based on existing scientific evidence, international expertise, and experience gained from previous examinations, the FLE is developed by experts from all five medical faculties in Switzerland with the support of the Institute for Medical Education and is held simultaneously at five locations. The exam organisers document and review every examination held and continuously optimise the processes; they have summarised the results in this report.Results: The essential steps comprise the development, revision and translation of questions; construction of the exam and production of materials; candidate preparation; implementation and analysis. The quality assurance measures consist of guideline coherence in the development of the questions and implementation of the exam, revision processes, construction of the exam based on the national blueprint, multiphase review of the translations and exam material, and statistical analysis of the exam and the comments from candidates. The intensive collaboration, especially on the part of representatives from all the participating faculties and a central coordination unit, which provides methodological support throughout and oversees the analysis of the exam, has proven successful. Successfully completed examinations and reliable results in the eleven examinations so far implemented represent the outcomes of the quality assurance measures. Significant insights in recent years are the importance of appreciating the work of those involved and the central organisation of exam development, thus ensuring the long-term success of the process.Conclusion: Common guidelines and workshops, quality assurance measures accompanied by the continuous improvement of all processes, and appreciation of everyone involved, are essential to carrying out such an examination at a high-quality level in the long term.Zielsetzung: Dieser Bericht beschreibt die zentralen Schritte der Erstellung, Durchführung, Auswertung und Qualitätssicherung des schriftlichen Teils der eidgenössischen Prüfung Humanmedizin (Schweizer Staatsexamen) sowie die seit deren Einführung 2011 gewonnenen Erkenntnisse.Methodik: Die eidgenössische Prüfung wird auf Basis vorhandener wissenschaftlicher Evidenz, internationaler Expertise sowie Erfahrungen aus vorhergehenden Prüfungen durch Experten aller fünf Medizinischen Fakultäten der Schweiz mit Unterstützung des Instituts für medizinische Lehre erstellt und gleichzeitig an fünf Standorten durchgeführt. Die Prüfungsorganisatoren dokumentieren und reflektieren jede Prüfungsdurchführung, optimieren die Prozesse kontinuierlich und haben die Ergebnisse in diesem Bericht zusammengefasst. Ergebnisse: Die zentralen Schritte umfassen: Fragenerstellung, -revision, -übersetzung; Prüfungszusammenstellung und Materialherstellung; Kandidatenvorbereitung; Prüfungsdurchführung und -auswertung. Die Qualitätssicherungsmassnahmen bestehen aus Richtlinienkohärenz bei der Fragenerstellung und Prüfungsdurchführung, Revisionsprozessen, Prüfungszusammenstellung auf Basis des nationalen Blueprints, mehrstufiger Überprüfung der Übersetzungen und des Prüfungsmaterials sowie der statistischen Auswertung der Prüfung und der Kandidatenkommentare. Bewährt hat sich dabei die enge Zusammenarbeit insbesondere von Vertretern aller beteiligten Fakultäten sowie einer zentralen Koordinationsstelle, die sämtliche Schritte methodisch begleitet und sich um die Auswertung der Prüfung kümmert. Die Endergebnisse der Qualitätssicherungsmassnahmen sind erfolgreiche Prüfungsdurchführungen und reliable Ergebnisse in den bisher elf so durchgeführten Prüfungen. Wichtige Erkenntnisse der vergangenen Jahre sind die Bedeutung der Wertschätzung der Arbeit der Beteiligten und die zentrale Organisation der Prüfungserstellung, um den Prozess langfristig erfolgreich durchzuführen. Schlussfolgerung: Um eine solche Prüfung langfristig mit hoher Qualität durchzuführen, sind gemeinsame Richtlinien und Workshops, Qualitätssicherungsmassnahmen mit fortlaufender Verbesserung aller Prozesse sowie die Wertschätzung der Beteiligten zentral