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Sonstige beteiligte Institutionen
Phase coexistence phenomena have been intensively studied in strongly correlated materials where several ordered states simultaneously occur or compete. Material properties critically depend on external parameters and boundary conditions, where tiny changes result in qualitatively different ground states. However, up to date, phase coexistence phenomena have exclusively been reported for complex compounds composed of multiple elements. Here we show that charge- and magnetically ordered states coexist in double-layer Fe/Rh(001). Scanning tunnelling microscopy and spectroscopy measurements reveal periodic charge-order stripes below a temperature of 130 K. Close to liquid helium temperature, they are superimposed by ferromagnetic domains as observed by spin-polarized scanning tunnelling microscopy. Temperature-dependent measurements reveal a pronounced cross-talk between charge and spin order at the ferromagnetic ordering temperature about 70 K, which is successfully modelled within an effective Ginzburg–Landau ansatz including sixth-order terms. Our results show that subtle balance between structural modifications can lead to competing ordering phenomena.
Topological insulators interacting with magnetic impurities have been reported to host several unconventional effects. These phenomena are described within the framework of gapping Dirac quasiparticles due to broken time-reversal symmetry. However, the overwhelming majority of studies demonstrate the presence of a finite density of states near the Dirac point even once topological insulators become magnetic. Here, we map the response of topological states to magnetic impurities at the atomic scale. We demonstrate that magnetic order and gapless states can coexist. We show how this is the result of the delicate balance between two opposite trends, that is, gap opening and emergence of a Dirac node impurity band, both induced by the magnetic dopants. Our results evidence a more intricate and rich scenario with respect to the once generally assumed, showing how different electronic and magnetic states may be generated and controlled in this fascinating class of materials.
Peptide Receptor Radionuclide Therapy (PRRT) for the treatment of neuroendocrine tumors may lead to kidney deterioration. This study aimed to evaluate the suitability of \(^{99m}\)Tc-mercaptoacetyltriglycine (\(^{99m}\)Tc-MAG3) clearance for the early detection of PRRT-induced changes on tubular extraction (TE). TE rate (TER) was measured prior to 128 PRRT cycles (7.6±0.4 GBq \(^{177}\)Lu-octreotate/octreotide each) in 32 patients. TER reduction during PRRT was corrected for age-related decrease and analyzed for the potential to predict loss of glomerular filtration (GF). The GF rate (GFR) as measure for renal function was derived from serum creatinine. The mean TER was 234 ± 53 ml/min/1.73 m² before PRRT (baseline) and 221 ± 45 ml/min/1.73 m² after a median follow-up of 370 days. The age-corrected decrease (mean: -3%, range: -27% to +19%) did not reach significance (p=0.09) but significantly correlated with the baseline TER (Spearman p=-0.62, p<0.001). Patients with low baseline TER showed an improved TER after PRRT, high decreases were only observed in individuals with high baseline TER. Pre-therapeutic TER data were inferior to plasma creatinine-derived GFR estimates in predicting late nephropathy. TER assessed by \(^{99m}\)Tc-MAG3clearance prior to and during PRRT is not suitable as early predictor of renal injury and an increased risk for late nephropathy.
FANCM is a highly conserved DNA remodeling enzyme that promotes the activation of the Fanconi anemia DNA repair pathway and facilitates replication traverse of DNA interstrand crosslinks. However, how FANCM interacts with the replication machinery to promote traverse remains unclear. Here, we show that FANCM and its archaeal homolog Hef from Thermoplasma acidophilum interact with proliferating cell nuclear antigen (PCNA), an essential co-factor for DNA polymerases in both replication and repair. The interaction is mediated through a conserved PIP-box; and in human FANCM, it is strongly stimulated by replication stress. A FANCM variant carrying a mutation in the PIP-box is defective in promoting replication traverse of interstrand crosslinks and is also inefficient in promoting FANCD2 monoubiquitination, a key step of the Fanconi anemia pathway. Our data reveal a conserved interaction mode between FANCM and PCNA during replication stress, and suggest that this interaction is essential for FANCM to aid replication machines to traverse DNA interstrand crosslinks prior to post-replication repair.
Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with \(^{18}\)F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR–PET/CT for detecting cardiac sarcoidosis in comparison to CMR.
15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUV\(_{mean}\)) and maximum standardized uptake values (SUV\(_{max}\)) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity.
SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR+/PET- subjects, one patient with minor involvement (<25% of wall thickness in CMR) was missed by PET. The remaining two CMR+/PET- patients displayed no adverse cardiac events during follow-up.
In the 17-segment model, PET/CT yielded 27 and CMR 29 positive segments. Overall concordance of the 2 modalities was 96.1% (245/255 segments analyzed). SUV\(_{mean}\) and SUV\(_{max}\) in inflamed areas were 2.0±1.2 and 2.6±1.2, respectively. The lesion-to-remote myocardium and lesion-to-LV cavity ratios were 1.8±0.2 and 1.9±0.2 for SUV\(_{mean}\) and 2.0±0.3 and 1.7±0.3 for SUV\(_{max}\), respectively.
Detection of cardiac sarcoidosis by SSTR-PET/CT is feasible. Our data warrant further analysis in larger prospective series.
Platelet-derived growth factor (PDGF) and signaling via its receptors plays a crucial role in tumor cell proliferation and thus may represent an attractive target besides VEGF/EGFR-based antibody therapies. In this study we analyzed the influence of PDGF in colorectal cancer. PDGF was expressed intensively in early and even more intensively in late stage primary CRCs. Like VEGF, PDGF enhanced human colon cancer proliferation, and increased oxidative glycolytic activity, and activated HIF1α and c-Myc in vitro. PDGF activated the PI3K/Akt/mTOR pathway while leaving MAPK signaling untouched. Further dissection showed that inhibition of Akt strongly impeded cancer cell growth while inhibition of PI3K did not. MAPK analysis suggested an inhibitory crosstalk between both pathways, thus explaining the different effects of the Akt and PI3K inhibitors on cancer cell proliferation. PDGF stimulates colon cancer cell proliferation, and prevents inhibitor induced apoptosis, resulting in tumor growth. Therefore inhibition of PDGF signaling seems to be a promising target in colorectal cancer therapy. However, due to the multifaceted nature of the intracellular PDGF signaling, careful intervention strategies are needed when looking into specific signaling pathways like PI3K/Akt/mTOR and MAPK.
The process of tumor invasion requires degradation of extracellular matrix by proteolytic enzymes. Cancer cells form protrusive invadopodia, which produce and release matrix metalloproteinases (MMPs) to degrade the basement membrane thereby enabling metastasis. We investigated the effect of LASP1, a newly identified protein in invadopodia, on expression, secretion and activation of MMPs in invasive breast tumor cell lines.
By analyzing microarray data of in-house generated control and LASP1-depleted MDA-MB-231 breast cancer cells, we observed downregulation of MMP1, -3 and -9 upon LASP1 depletion. This was confirmed by Western blot analysis. Conversely, rescue experiments restored in part MMP expression and secretion. The regulatory effect of LASP1 on MMP expression was also observed in BT-20 breast cancer cells as well as in prostate and bladder cancer cell lines.
In line with bioinformatic FunRich analysis of our data, which mapped a high regulation of transcription factors by LASP1, public microarray data analysis detected a correlation between high LASP1 expression and enhanced c-Fos levels, a protein that is part of the transcription factor AP-1 and known to regulate MMP expression. Compatibly, in luciferase reporter assays, AP-1 showed a decreased transcriptional activity after LASP1 knockdown.
Zymography assays and Western blot analysis revealed an additional promotion of MMP secretion into the extracellular matrix by LASP1, thus, most likely, altering the microenvironment during cancer progression.
The newly identified role of LASP1 in regulating matrix degradation by affecting MMP transcription and secretion elucidated the migratory potential of LASP1 overexpressing aggressive tumor cells in earlier studies.
In the present work, a simulation system is proposed that can be used as an educational tool by physicians in training basic skills of minimally invasive vascular interventions. In order to accomplish this objective, initially the physical model of the wire proposed by Konings has been improved. As a result, a simpler and more stable method was obtained to calculate the equilibrium configuration of the wire. In addition, a geometrical method is developed to perform relaxations. It is particularly useful when the wire is hindered in the physical method because of the boundary conditions. Then a recipe is given to merge the physical and the geometrical methods, resulting in efficient relaxations. Moreover, tests have shown that the shape of the virtual wire agrees with the experiment. The proposed algorithm allows real-time executions, and furthermore, the hardware to assemble the simulator has a low cost.
Background
Fibromyalgia syndrome (FMS) is a complex chronic condition that makes high demands on patients’ self-management skills. Thus, patient education is considered an important component of multimodal therapy, although evidence regarding its effectiveness is scarce. The main objective of this study is to assess the effectiveness of an advanced self-management patient education program for patients with FMS as compared to usual care in the context of inpatient rehabilitation.
Methods/Design
We conducted a multicenter cluster randomized controlled trial in 3 rehabilitation clinics. Clusters are groups of patients with FMS consecutively recruited within one week after admission. Patients of the intervention group receive the advanced multidisciplinary self-management patient education program (considering new knowledge on FMS, with a focus on transfer into everyday life), whereas patients in the control group receive standard patient education programs including information on FMS and coping with pain. A total of 566 patients are assessed at admission, at discharge and after 6 and 12 months, using patient reported questionnaires. Primary outcomes are patients’ disease- and treatment-specific knowledge at discharge and self-management skills after 6 months. Secondary outcomes include satisfaction, attitudes and coping competences, health-promoting behavior, psychological distress, health impairment and participation. Treatment effects between groups are evaluated using multilevel regression analysis adjusting for baseline values.
Discussion
The study evaluates the effectiveness of a self-management patient education program for patients with FMS in the context of inpatient rehabilitation in a cluster randomized trial. Study results will show whether self-management patient education is beneficial for this group of patients.
Cofacial positioning of two perylene bisimide (PBI) chromophores at a distance of 6.5 angstrom in a cyclophane structure prohibits the otherwise common excimer formation and directs photoexcited singlet state relaxation towards intramolecular symmetry-breaking charge separation (τ\(_{CS}\) = 161 +/- 4 ps) in polar CH\(_2\)Cl\(_2\), which is thermodynamically favored with a Gibbs free energy of ΔG\(_{CS}\) = -0.32 eV. The charges then recombine slowly in τ\(_{CR}\) = 8.90 +/- 0.06 ns to form the PBI triplet excited state, which can be used subsequently to generate singlet oxygen in 27% quantum yield. This sequence of events is eliminated by dissolving the PBI cyclophane in non-polar toluene, where only excited singlet state decay occurs. In contrast, complexation of electron-rich aromatic hydrocarbons by the host PBI cyclophane followed by photoexcitation of PBI results in ultrafast electron transfer (<10 ps) from the guest to the PBI in CH\(_2\)Cl\(_2\). The rate constants for charge separation and recombination increase as the guest molecules become easier to oxidize, demonstrating that charge separation occurs close to the peak of the Marcus curve and the recombination lies far into the Marcus inverted region.
The quantum efficiency of light emission is a crucial parameter of supramolecular aggregates that can be tuned by the molecular design of the monomeric species. Here, we report on a strong variation of the fluorescence quantum yield due to different phases of aggregation for the case of a perylene bisimide dye. In particular, a change of the dominant aggregation character from H- to J-type within the first aggregation steps is found, explaining the observed dramatic change in quantum yield. This behaviour is rationalised by means of a systematic study of the intermolecular potential energy surfaces using the time-dependent density functional based tight-binding (TD-DFTB) method. This provides a correlation between structural changes and a coupling strength and supports the notion of H- type stacked dimers and J-type stack-slipped dimers. The exciton-vibrational level structure is modelled by means of an excitonic dimer model including two effective vibrational modes per monomer. Calculated absorption and fluorescence spectra are found to be in reasonable agreement with experimental ones, thus supporting the conclusion on the aggregation behaviour.
The bis(N-heterocyclic carbene)(diphenylacetylene)palladium complex Pd(ITMe)\(_2\)(PhCCPh)] (ITMe=1,3,4,5-tetramethylimidazol-2-ylidene) acts as a highly active pre-catalyst in the diboration and silaboration of azobenzenes to synthesize a series of novel functionalized hydrazines. The reactions proceed using commercially available diboranes and silaboranes under mild reaction conditions.
A perylene bisimide dye bearing amide functionalities at the imide positions derived from amino acid L-alanine and a dialkoxy-substituted benzyl amine self-assembles into tightly bound dimers by π-π-stacking and hydrogen bonding in chloroform. In less polar or unpolar solvents like toluene and methylcyclohexane, and in their mixtures, these dimers further self-assemble into extended oligomeric aggregates in an anti-cooperative process in which even numbered aggregates are highly favoured. The stepwise transition from dimers into oligomers can not be properly described by conventional K\(_2\)-K model, and thus a new K\(_2\)-K aggregation model has been developed, which interpretes the present anti-cooperative supramolecular polymerization more appropriately. The newly developed K\(_2\)-K model will be useful to describe self-assembly processes of a plethora of other π-conjugated molecules that are characterized by a favored dimer species.
Treatment of an anionic dimanganaborylene complex ([{Cp(CO)\(_2\)Mn}\(_2\)B]\(^-\)) with coinage metal cations stabilized by a very weakly coordinating Lewis base (SMe\(_2\)) led to the coordination of the incoming metal and subsequent displacement of dimethylsulfide in the formation of hexametalladiborides featuring planar four-membered M\(_2\)B\(_2\) cores (M = Cu, Au) comparable to transition metal clusters constructed around four-membered rings composed solely of coinage metals. The analogies between compounds consisting of B\(_2\)M\(_2\) units and M\(_4\) (M = Cu, Au) units speak to the often overlooked metalloid nature of boron. Treatment of one of these compounds (M = Cu) with a Lewis-basic metal fragment (Pt(PCy\(_3\))\(_2\)) led to the formation of a tetrametallaboride featuring two manganese, one copper and one platinum atom, all bound to boron in a geometry not yet seen for this kind of compound. Computational examination suggests that this geometry is the result of d\(^{10}\)-d\(^{10}\) dispersion interactions between the copper and platinum fragments.
Herein, we describe the selective formation of a stable neutral spiroborate radical by one-electron oxidation of the corresponding tetraorganoborate salt Li[B(C\(_4\)Ph\(_4\))\(_2\)], formally containing a tetrahedral borate centre and a s-cis-butadiene radical cation as the spin-bearing site. Spectroscopic and computational methods have been used to determine the spin distribution and the chromism observed in the solid state.
Perylene bisimide hydrogels and lyotropic liquid crystals with temperature-responsive color change
(2016)
The self-assembly of perylene bisimide (PBI) dyes bearing oligo ethylene glycol (OEG) units in water affords responsive functional nanostructures characterized by their lower critical solution temperature (LCST). Tuning of the LCST is realized by a supramolecular approach that relies on two structurally closely related PBI–OEG molecules. The two PBIs socially co-assemble in water and the resulting nanostructures exhibit a single LCST in between the transition temperatures of the aggregates formed by single components. This permits to precisely tune the transition from a hydrogel to a lyotropic liquid crystal state at temperatures between 26 and 51 °C by adjusting the molar fraction of the two PBIs. Owing to concomitant changes in PBI–PBI interactions this phase transition affords a pronounced color change with “fluorescence-on” response that can be utilized as a smart temperature sensory system.
A site specific perturbation of a photo-excited molecular aggregate can lead to a localization of excitonic energy. We investigate this localization dynamics for laser-prepared excited states. Changing the parameters of the electric field significantly influences the exciton localization which offers the possibility for a selective control of this process. This is demonstrated for aggregates possessing a single vibrational degree of freedom per monomer unit. It is shown that the effects identified for the molecular dimer can be generalized to larger aggregates with a high density of vibronic states.
The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake
(2016)
Carnivorous plants, such as the Venus flytrap (Dionaea muscipula), depend on an animal diet when grown in nutrient-poor soils. When an insect visits the trap and tilts the mechanosensors on the inner surface, action potentials (APs) are fired. After a moving object elicits two APs, the trap snaps shut, encaging the victim. Panicking preys repeatedly touch the trigger hairs over the subsequent hours, leading to a hermetically closed trap, which via the gland-based endocrine system is flooded by a prey-decomposing acidic enzyme cocktail. Here, we asked the question as to how many times trigger hairs have to be stimulated (e.g., now many APs are required) for the flytrap to recognize an encaged object as potential food, thus making it worthwhile activating the glands. By applying a series of trigger-hair stimulations, we found that the touch hormone jasmonic acid (JA) signaling pathway is activated after the second stimulus, while more than three APs are required to trigger an expression of genes encoding prey-degrading hydrolases, and that this expression is proportional to the number of mechanical stimulations. A decomposing animal contains a sodium load, and we have found that these sodium ions enter the capture organ via glands. We identified a flytrap sodium channel DmHKT1 as responsible for this sodium acquisition, with the number of transcripts expressed being dependent on the number of mechano-electric stimulations. Hence, the number of APs a victim triggers while trying to break out of the trap identifies the moving prey as a struggling Na+-rich animal and nutrition for the plant.
Ficaria calthifolia (diploide Form, Typ1) wurde kürzlich nord-westlich des geschlossenen südosteuropäischen Verbreitungsgebiet auch in Deutschland gefunden, nämlich in Würzburg (2006) und an Elbedeichen in Brandenburg (2014) und Sachsen (2015). Ficaria calthifolia ist durch das Fehlen von verlängerten mehrgliedrigen Stängeln und die Abwesenheit von Brutknollen in den Blattachseln gekennzeichnet. Die 1–2 (3) Stängel von Ficaria calthifolia verbleiben überwiegend im Boden (hypogäisch), können aber im Laufe der Anthese aus dem Boden hervorwachsen. Die gestielten Laubblätter setzen sich aus Grundblättern und einer Rosette von bis zu 8 Stängelblättern pro Stängel zusammen. Letztere entspringen aus dem terminalen Stängelknoten (Stängelblatt-rosette). In Würzburg kommen zwei Populationen von Ficaria calthifolia vor, diploide Typ1-Pflanzen und triploide Typ2-Pflanzen. Letztere sind robuster, besitzen größere Blüten (bis 4 cm) und entwickeln nur vereinzelte reife Nüsschen. Pflanzen mit höherem Ploidiegrad (wahrscheinlich pentaploid, Typ3) wurden auch gefunden. Etwa 60% der 3 bis 8 Blütenstiele von Typ1-Pflanzen besitzt kein Stängelblatt, der Rest einen Knoten mit 1 bis 2 (3) Hochblättern. Die Zahl der Kronblätter beträgt 8 (vereinzelt 9), die durchschnittliche Zahl reifer, eiförmiger Nüsschen pro Fruchtstand beträgt 7 (Würzburg) / 14 (Elbe) (maximal 26). Aus vom Rhizom abgebrochenen und im Mai gepflanzten Speicherknollen keimten im Spätherbst desselben Jahrs neue Pflanzen. Der Jahreszyklus des Wurzelsystems wird beschrieben. Durch spontane Ablösungen einzelner Speicherknollen findet eine vegetative Vermehrung statt. Neben Nüsschen wären abgebrochene Speicherknollen für die Fernansiedlung der Sippe an Elbe (u.a. Verschleppung durch Hochwasser) und Main (Verschleppung durch Schiffe und andere Vektoren) ausreichend.