Exploiting Locally Imposed Anisotropies in (Ga,Mn)As: a Non-volatile Memory Device

Progress in (Ga,Mn)As lithography has recently allowed us to realize structures where unique magnetic anisotropy properties can be imposed locally in various regions of a given device. We make use of this technology to fabricate a device in which we study transport through a constriction separating two regions whose magnetization direction differs by 90 degrees. We find that the resistance of the constriction depends on the flow of the magnetic field lines in the constriction region and demonstrate that such a structure constitutes a non-volatile memory device

DKK1 inhibits canonical Wnt signaling in human papillomavirus-positive penile cancer cells

Penile squamous cell cancer (PSCC) is the most frequent penile malignant disease. Infections with human papillomaviruses (HPV) are a major etiologic driver of PSCC. However, the molecular details of the underlying carcinogenesis are understudied because of rare clinical specimens and missing cell lines. Here, we investigated if the expression of high-risk HPV16 oncogenes causes an augmentation of the Wnt pathway using unique HPV-positive penile cancer (PeCa) cell lines in monolayer and organotypic 3D raft cultures as well as tissue micro arrays containing clinical tissue specimens. The HPV oncoproteins enhanced the expression of Leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) and the HPV-positive PeCa cells expressed a signature of Wnt target and stemness-associated genes. However, the notable lack of nuclear β-catenin in vitro and in situ raised the question if the enhanced expression of Wnt pathway factors is tantamount to an active Wnt signaling. Subsequent TOP-flash reporter assays revealed Wnt signaling as absent and not inducible by respective Wnt ligands in PeCa cell lines. The HPV-positive PeCa cells and especially HPV-positive PeCa specimens of the tumor core expressed the Wnt antagonist and negative feedback-regulator Dickkopf1 (DKK1). Subsequent neutralization experiments using PeCa cell line-conditioned media demonstrated that DKK1 is capable to impair ligand-induced Wnt signaling. While gene expression analyses suggested an augmented and active canonical Wnt pathway, the respective signaling was inhibited due to the endogenous expression of the antagonist DKK1. Subsequent TMA stainings indicated Dkk1 as linked with HPV-positivity and metastatic disease progression in PeCa suggesting potential as a prognostic marker

Selbstorganisation von Amphiphilen auf Basis von Hexaphenylbenzol und Hexa-peri-hexabenzocoronen

Die Selbstorganisation von amphiphilen Molekülen wird genutzt, um in Lösung, auf der Oberfläche, in der festen Phase und an der Flüssig/Fest-Grenzfläche nanoskopisch strukturierte Materialien zu erhalten. Ziel hierbei ist es, die Dynamik der niedermolekularen Amphiphile mit der Stabilität der hochmolekularen Amphiphile zu vereinigen, um damit die Selbstorganisation der Moleküle zu kontrollieren. Drei Konzepte zur Strukturierung von Kohlenstoff durch Selbstorganisation werden vorgestellt. Im ersten Konzept werden aus Hexaphenylbenzol-Polyethylenglykol- (HPB-PEG) und Hexa-peri-hexabenzocoronen- (HBC-PEG) Derivaten wurmähnliche bzw. faserförmige Strukturen in wässriger Lösung erhalten. Der Wassergehalt in den Hydrogelfasern aus den HPB-PEG-Derivaten kann durch das Substitutionsmuster der Amphiphile und die Länge der PEG-Ketten eingestellt werden. Die Hydrogelfasern ähneln anders als die bisherigen Verfahren, die zur Faserherstellung verwendet werden (Extrudieren, Mikrofluid-Verarbeitung oder Elektrospinning), Systemen in der Natur. Der Beweis für die Bildung von Hydrogelfasern wird mittels spezieller Methoden der polarisierten und depolarisierten dynamischen Lichtstreuung erbracht. Im zweiten Konzept werden durch Elektronenbestrahlung und Pyrolyse von 3',4',5',6'-Tetraphenyl-[1,1':2',1''-terphenyl]-4,4''-dithiol homogene Kohlenstoffmembranen mit Poren erzeugt, die Anwendung in der Filtration finden können und im dritten Konzept wird die Selbstorganisation von einem ortho-verknüpften HPB-Trimer an der Flüssig/Fest-Grenzfläche untersucht. Auf diese Weise werden hochgeordnete lamellare Strukturen erhalten. In allen drei Konzepten sind die Geometrie und die Größe der Moleküle die entscheidenden Parameter zur Erzeugung definierter Strukturen.Self-assembly of amphiphiles is used as a tool for structuring materials in solution, on the surface, in the solid phase and at the liquid-solid interface. The aim of this work is to combine the dynamics of low-molecular weight amphiphiles with the stability of their high-molecular weight analogues in order to control the self-assembly of these molecules.Three concepts for structuring carbon by self-assembly are presented. In the first concept hexaphenylbenzene-polyethylene glycol (HPB-PEG) and hexa-peri-hexabenzocoronene-polyethylene glycol (HBC-PEG) derivatives lead to worm- or fiber-like structures in aqueous solution. The water content in the hydrogel fibers of HPB-PEG derivatives can be controlled by the substitution pattern of the amphiphile and by the length of the PEG chains. The hydrogel fiber formation by self-assembly is similar to systems in nature in contrast to conventional fiber formation processes such as extruding, microfluidic processes or electrospinning. The hydrogel fiber formation is verified by special analytical methods of polarized and depolarized dynamic light scattering. In the second concept, homogeneous porous carbon membranes are obtained after electron-irradiation and pyrolysis of 3',4',5',6'-tetraphenyl-[1,1':2',1''-terphenyl]-4,4''-dithiol. These membranes could be applied as filters. In the third concept, the self-assembly of an ortho-connected HPB trimer is investigated at the liquid-solid-interface. In this way, highly-ordered lamellar structures are prepared. In all three concepts, geometry and size of the molecules are decisive parameters for the formation of defined structures

Konvergenzbeschleunigung für Binomialmethoden zur Bewertung von Barriereoptionen

Für die Bewertung zahlreicher Barriereoptionen stehen keine analytischen Preisformeln zur Verfügung. Ein mögliches Näherungsverfahren, welches für die Bepreisung eingesetzt werden kann, ist das Binomialmodell. Dieser Artikel analysiert die bei der binomialen Bewertung von Barriereoptionen auftretende Sägezahnkonvergenz. Es werden vier Verfahren mit verbesserten Konvergenzverhalten beschrieben. Dabei stellt sich heraus, daß durch alle betrachteten Verfahren eine deutliche Konvergenzbeschleunigung erreicht werden kann. Numerische Beispiele illustrieren die vorgestellten Verfahren

Ubiquitin-proteasome-system and enzymes of energy metabolism in skeletal muscle of patients with HFpEF and HFrEF

Abstract Background Skeletal muscle (SM) alterations contribute to exercise intolerance in heart failure patients with preserved (HFpEF) or reduced (HFrEF) left ventricular ejection fraction (LVEF). Protein degradation via the ubiquitin‐proteasome‐system (UPS), nuclear apoptosis, and reduced mitochondrial energy supply is associated with SM weakness in HFrEF. These mechanisms are incompletely studied in HFpEF, and a direct comparison between these groups is missing. Methods and results Patients with HFpEF (LVEF ≥ 50%, septal E/e′ > 15 or >8 and NT‐proBNP > 220 pg/mL, n = 20), HFrEF (LVEF ≤ 35%, n = 20) and sedentary control subjects (Con, n = 12) were studied. Inflammatory markers were measured in serum, and markers of the UPS, nuclear apoptosis, and energy metabolism were determined in percutaneous SM biopsies. Both HFpEF and HFrEF showed increased proteolysis (MuRF‐1 protein expression, ubiquitination, and proteasome activity) with proteasome activity significantly related to interleukin‐6. Proteolysis was more pronounced in patients with lower exercise capacity as indicated by peak oxygen uptake in per cent predicted below the median. Markers of apoptosis did not differ between groups. Mitochondrial energy supply was reduced in HFpEF and HFrEF (complex‐I activity: −31% and −53%; malate dehydrogenase activity: −20% and −29%; both P < 0.05 vs. Con). In contrast, short‐term energy supply via creatine kinase was increased in HFpEF but decreased in HFrEF (47% and −45%; P < 0.05 vs. Con). Conclusions Similarly to HFrEF, skeletal muscle in HFpEF is characterized by increased proteolysis linked to systemic inflammation and reduced exercise capacity. Energy metabolism is disturbed in both groups; however, its regulation seems to be severity‐dependent

Poly(ethylene glycol)-Functionalized Hexaphenylbenzenes as Unique Amphiphiles: Supramolecular Organization and Ion Conductivity

The synthesis of a series of propeller-shaped hexaphenylbenzenes (HPB) substituted with one (<b>3</b>), two (<b>1</b>) and four (<b>2</b>) poly­(ethylene glycol) (PEG) chains as well as of an ortho-connected trimer of HPBs bearing two PEG chains (<b>4</b>) result in remarkable amphiphiles with supramolecular organization and suppressed dynamics. The thermodynamic state and self-assembly are studied with DSC and X-ray diffraction whereas the dynamics of HPB core and PEG segments are elucidated via heteronuclear NMR and dielectric spectroscopy. The phase state is largely determined by the rod–coil nature and architecture of block copolymers comprising a HPB “mesogen’ and flexible PEG chains. In addition, the molecular shape of the ortho-connected trimer of HPBs (<b>4</b>) promotes π–π stacking and gives rise to a supramolecular columnar organization uncommon to most other HPBs. The emerging dynamic picture is that of practically frozen HPB cores that are surrounded by mobile PEG segments. The implications of this supramolecular organizationstacked/immobile HPB cores and flexible/fast moving PEG segments with suppressed crystallinityto ion transport are discussed with respect to the conductivity measurements in amphiphiles doped with LiCF₃SO₃ salt at different [EG]:[Li⁺] ratios. A unique feature of the doped amphiphiles is the Vogel–Fulcher–Tammann temperature dependence of ionic conductivity with values that are comparable to the archetypal polymer electrolyte (PEG)_<i>x</i>LiCF₃SO₃

Chance or challenge, spoilt for choice? New recommendations on diagnostic and therapeutic considerations in hereditary transthyretin amyloidosis with polyneuropathy: the German/Austrian position and review of the literature

Hereditary transthyretin amyloidosis is caused by pathogenic variants (ATTR(v)) in the TTR gene. Alongside cardiac dysfunction, the disease typically manifests with a severely progressive sensorimotor and autonomic polyneuropathy. Three different drugs, tafamidis, patisiran, and inotersen, are approved in several countries, including the European Union and the United States of America. By stabilizing the TTR protein or degrading its mRNA, all types of treatment aim at preventing amyloid deposition and stopping the otherwise fatal course. Therefore, it is of utmost importance to recognize both onset and progression of neuropathy as early as possible. To establish recommendations for diagnostic and therapeutic procedures in the follow-up of both pre-symptomatic mutation carriers and patients with manifest ATTR(v) amyloidosis with polyneuropathy, German and Austrian experts elaborated a harmonized position. This paper is further based on a systematic review of the literature. Potential challenges in the early recognition of disease onset and progression are the clinical heterogeneity and the subjectivity of sensory and autonomic symptoms. Progression cannot be defined by a single test or score alone but has to be evaluated considering various disease aspects and their dynamics over time. The first-line therapy should be chosen based on individual symptom constellations and contra-indications. If symptoms worsen, this should promptly implicate to consider optimizing treatment. Due to the rareness and variability of ATTR(v) amyloidosis, the clinical course is most importantly directive in doubtful cases. Therefore, a systematic follow-up at an experienced center is crucial to identify progression and reassure patients and carriers

A Universal Scheme to Convert Aromatic Molecular Monolayers into Functional Carbon Nanomembranes

Free-standing nanomembranes with molecular or atomic thickness are currently explored for separation technologies, electronics, and sensing. Their engineering with well-defined structural and functional properties is a challenge for materials research. Here we present a broadly applicable scheme to create mechanically stable carbon nanomembranes (CNMs) with a thickness of ∼0.5 to ∼3 nm. Monolayers of polyaromatic molecules (oligophenyls, hexaphenylbenzene, and polycyclic aromatic hydrocarbons) were assembled and exposed to electrons that cross-link them into CNMs; subsequent pyrolysis converts the CNMs into graphene sheets. In this transformation the thickness, porosity, and surface functionality of the nanomembranes are determined by the monolayers, and structural and functional features are passed on from the molecules through their monolayers to the CNMs and finally on to the graphene. Our procedure is scalable to large areas and allows the engineering of ultrathin nanomembranes by controlling the composition and structure of precursor molecules and their monolayers