There is a debate if electricity markets on the basis of energy-only markets ensure a sufficient generation capacity. Various capacity mechanisms are discussed to tackle this potential problem. ...Capacity auctions with reliability options are seen as one market-based solution. Assuming a perfect energy-only market, this mechanism leads to an equilibrium with an optimal capacity mix. This optimum is missed if there are distorted price signals at the electricity market. This is a serious problem since, despite substantial cost reductions, renewable-based electricity generation still depends on subsidies, which are not internalized at electricity markets. We develop a capacity market that internalizes subsidies for RES without direct intervention in the electricity market. The result is an endogenous discrimination of capacity prices, which enhances acceptance for a capacity market. Arising incentives direct the capacity mix to an equilibrium where discriminated prices converge to one uniform capacity price. The equilibrium is the optimal answer of fossil capacity to RES-based electricity generation.
Zusammenfassung
Die tief infiltrierende Endometriose (TIE) ist mit Fertilitätsstörungen assoziiert, die operative Therapie mit teils schwerwiegenden Komplikationen. Zur Verbesserung der Fertilität ...stehen Maßnahmen der assistierten Reproduktion zur Verfügung. Bei eingeschränkter Datenlage scheint die Operation bei TIE ebenfalls eine Verbesserung der Fertilität zu bewirken. Erreichbar sind insbesondere die Möglichkeit einer spontanen Schwangerschaft, einer Schwangerschaft nach frustraner reproduktionsmedizinischer Behandlung, aber auch die zusätzliche Verbesserung der Fertilität trotz Durchführung von Maßnahmen der assistierten Reproduktion. Bei der Behandlungsplanung muss auch das Vorhandensein einer Adenomyosis berücksichtigt werden. Das Vorgehen bei TIE und Infertilität muss individuell geplant werden.
Fibrosis is a common pathology in many cardiac disorders and is driven by the activation of resident fibroblasts. The global posttranscriptional mechanisms underlying fibroblast-to-myofibroblast ...conversion in the heart have not been explored.
Genome-wide changes of RNA transcription and translation during human cardiac fibroblast activation were monitored with RNA sequencing and ribosome profiling. We then used RNA-binding protein-based analyses to identify translational regulators of fibrogenic genes. The integration with cardiac ribosome occupancy levels of 30 dilated cardiomyopathy patients demonstrates that these posttranscriptional mechanisms are also active in the diseased fibrotic human heart.
We generated nucleotide-resolution translatome data during the transforming growth factor β1-driven cellular transition of human cardiac fibroblasts to myofibroblasts. This identified dynamic changes of RNA transcription and translation at several time points during the fibrotic response, revealing transient and early-responder genes. Remarkably, about one-third of all changes in gene expression in activated fibroblasts are subject to translational regulation, and dynamic variation in ribosome occupancy affects protein abundance independent of RNA levels. Targets of RNA-binding proteins were strongly enriched in posttranscriptionally regulated genes, suggesting genes such as MBNL2 can act as translational activators or repressors. Ribosome occupancy in the hearts of patients with dilated cardiomyopathy suggested the same posttranscriptional regulatory network was underlying cardiac fibrosis. Key network hubs include RNA-binding proteins such as Pumilio RNA binding family member 2 (PUM2) and Quaking (QKI) that work in concert to regulate the translation of target transcripts in human diseased hearts. Furthermore, silencing of both PUM2 and QKI inhibits the transition of fibroblasts toward profibrotic myofibroblasts in response to transforming growth factor β1.
We reveal widespread translational effects of transforming growth factor β1 and define novel posttranscriptional regulatory networks that control the fibroblast-to-myofibroblast transition. These networks are active in human heart disease, and silencing of hub genes limits fibroblast activation. Our findings show the central importance of translational control in fibrosis and highlight novel pathogenic mechanisms in heart failure.
Endometriosis is a painful gynecological condition characterized by ectopic growth of endometrial cells. Little is known about its pathogenesis, which is partially due to a lack of suitable ...experimental models. Here, we use endometrial stromal (St-T1b), primary endometriotic stromal, epithelial endometriotic (12Z) and co-culture (1:1 St-T1b:12Z) spheroids to mimic the architecture of endometrium, and either collagen I or Matrigel to model ectopic locations. Stromal spheroids, but not single cells, assumed coordinated directional migration followed by matrix remodeling of collagen I on day 5 or 7, resembling ectopic lesions. While generally a higher area fold increase of spheroids occurred on collagen I compared to Matrigel, directional migration was not observed in co-culture or in 12Z cells. The fold increase in area on collagen I was significantly reduced by MMP inhibition in stromal but not 12Z cells. Inhibiting ROCK signalling responsible for actomyosin contraction increased the fold increase of area and metabolic activity compared to untreated controls on Matrigel. The number of protrusions emanating from 12Z spheroids on Matrigel was decreased by microRNA miR-200b and increased by miR-145. This study demonstrates that spheroid assay is a promising pre-clinical tool that can be used to evaluate small molecule drugs and microRNA-based therapeutics for endometriosis.
Zusammenfassung
Die operative Therapie stellt eine der Hauptsäulen der Endometriosebehandlung dar. Operationen werden insbesondere bei Schmerzen und Sterilität durchgeführt und führen zu ...Schmerzlinderung, teilweise auch zu erhöhter Fertilität. Erläutert wird die operative Therapie bei Adenomyosis, peritonealer Endometriose, tief infiltrierender Endometriose und ovarieller Endometriose. Dabei werden die Effekte der Operation auf Schmerzen und Fertilität sowie Rezidive und Risiken diskutiert. Bei Adenomyosis kommen organerhaltende Verfahren und die Hysterektomie zum Einsatz. Bei peritonealer Endometriose wird die Komplettresektion angestrebt, bei tief infiltrierender Endometriose symptomorientierte Komplettresektion. Hierfür kommen zum Teil hochkomplexe Eingriffe mit erhöhtem Komplikationspotenzial zum Einsatz. Bei der ovariellen Endometriose wird die komplette Zystektomie angestrebt. Dabei sind ovarielle Funktion und Kinderwunsch zusätzlich zu beachten. Endometrioseoperationen sind zumindest kurz- bis mittelfristig effektiv hinsichtlich von Schmerzsymptomen. Sie erhöhen die Wahrscheinlichkeit einer Spontankonzeption. Ihre Rolle im Rahmen der assistierten Reproduktion ist noch unklar. Die Indikationsstellung zur Operation sollte daher stets individuell erfolgen. Die Behandlung sollte insbesondere bei tief infiltrierender Endometriose in spezialisierten Zentren erfolgen.
Abstract Endometriosis is characterized by growth of endometrial tissue at ectopic locations. Down-regulation of microRNA miR-200b is observed in endometriosis and malignant disease, driving tumour ...cells towards an invasive state by enhancing epithelial-to-mesenchymal transition (EMT). miR-200b up-regulation may inhibit EMT and invasive growth in endometriosis. To study its functional impact on the immortalized endometriotic cell line 12Z, the stromal cell line ST-T1b, and primary endometriotic stroma cells, a transient transfection approach with microRNA precursors was employed. Expression of bioinformatically predicted targets of miR-200b was analysed by qPCR. The cellular phenotype was monitored by Matrigel invasion assays, digital-holographic video microscopy and flow cytometry. qPCR revealed significant down-regulation of ZEB1 ( P < 0.05) and ZEB2 ( P < 0.01) and an increase in E-cadherin ( P < 0.01). miR-200b overexpression decreased invasiveness ( P < 0.0001) and cell motility ( P < 0.05). In contrast, cell proliferation ( P < 0.0001) and the stemness-associated side population phenotype ( P < 0.01) were enhanced following miR-200b transfection. These properties were possibly due to up-regulation of the pluripotency-associated transcription factor KLF4 ( P < 0.05) and require attention when considering therapeutic strategies. In conclusion, up-regulation of miR-200b reverts EMT, emerging as a potential therapeutic approach to inhibit endometriotic cell motility and invasiveness.
The use and implementation of nanocrystals (NCs) are highly dependent on the development of robust strategies capable of delivering high-quality NCs in the form of stable colloids. In particular, ...oxide perovskites offer numerous chemical structures and physical properties that are highly interesting for material science. This work explores a synthesis route capable of producing different perovskite NCs with sizes of less than 10 nm. These NCs show good colloidal stability in polar solvents with a shelf life longer than 1 year. The synthesis protocol is further studied with nuclear magnetic resonance (NMR) and gas chromatography–mass spectrometry (GC-MS) and optimized by design of experiments (DoE) statistics.
Individual single-walled carbon nanotubes (SWNTs) of (6,5) chirality were investigated by means of optical spectroscopy while their charge state was controlled electrochemically. The ...photoluminescence of the SWNTs was found to be quenched at positive and negative potentials, where the onset and offset varied for each individual SWNT. We propose that differences in the local environment of the individual SWNT lead to a shift of the Fermi energy, resulting in a distribution of the oxidation and reduction potentials. The exciton emission energy was found to correlate with the oxidation and reduction potential. Further proof of a correlation was found by deliberately doping individual SWNTs and monitoring their photoluminescence spectral shift.
Ovarian cancer (OC) is the eighth cancer both in prevalence and mortality in women and represents the deadliest female reproductive cancer. Due to generally vague symptoms, OC is frequently diagnosed ...only at a late and advanced stage, resulting in high mortality. The tumor extracellular matrix and cellular matrix receptors play a key role in the pathogenesis of tumor progression. Syndecans are a family of four transmembrane heparan sulfate proteoglycans (PG), including syndecan-1, -2, -3, and -4, which are dysregulated in a myriad of cancers, including OC. Many clinicopathological studies suggest that these proteins are promising diagnostic and prognostic biomarkers for OC. Furthermore, functions of the syndecan family in the regulation of cellular processes make it an interesting pharmacological target for anticancer therapies.
A combination of electrostatic force microscopy and optical microscopy was used to investigate the charge state of individual CdSe nanowires upon local illumination with a focused laser beam. The ...nanowires were found to be positively charged at the excitation spot and negatively charged at the distant end(s). For high laser powers, the amount of accumulated charges increases logarithmically with the laser power. These effects are described by a diffusion-based model where the results are in good agreement with the experimentally observed effects. On the basis of this model the charge imbalance along the nanowire should establish in the course of nanoseconds. The net charge separation within homogeneous nanowires upon local illumination is of importance for several electronic devices.
PDF
