Marktorientierte Vertriebs-Reorganisation von Energieversorgungsunternehmen

Seit der Liberalisierung des Energiemarktes im Jahre 1998 sehen sich Energieversorgungsunternehmen (EVUs) einer veränderten Markt- und Wettbewerbssituation gegenüber. Neben Risiken, wie dem Eintritt von Wettbewerbern in das vormals geschützte Gebiet, eröffnete sich ihnen hierdurch aber auch die Chance, außerhalb des eigenen Netzbereiches neue Kunden zu gewinnen. Um sowohl dem Margenverfall als auch der direkten Vergleichbarkeit mit scheinbar austauschbaren Leistungen der Wettbewerber entgegenzuwirken, erweist sich für EVUs eine Differenzierung durch stärkere Kundenorientierung als notwendig. Hiermit verbunden ist eine umfassende Neuausrichtung der Vertriebsorganisation. Nach einer Diskussion der zentralen Problemfelder im Organisationsbereich der heutigen EVUs wird anhand einer sechsstufigen Vorgehensweise aufgezeigt, wie EVUs die Aufbau- und Ablauforganisation (Strukturen und Prozesse) des Vertriebes konsequent am Markt ausrichten können. Eine Illustrierung der Vorgehensweise durch praxisnahe Beispiele erfolgt hierbei ebenso wie eine Darstellung der zentralen Erfolgsfaktoren einer jeden Stufe

Controlling antiferromagnetic domains in patterned La0.7Sr0.3FeO3 thin films

Transition metal oxide thin films and heterostructures are promising platforms to achieve full control of the antiferromagnetic (AFM) domain structure in patterned features as needed for AFM spintronic devices. In this work, soft x-ray photoemission electron microscopy was utilized to image AFM domains in micromagnets patterned into La0.7Sr0.3FeO3 (LSFO) thin films and La0.7Sr0.3MnO3 (LSMO)/LSFO superlattices. A delicate balance exists between magnetocrystalline anisotropy, shape anisotropy, and exchange interactions such that the AFM domain structure can be controlled using parameters such as LSFO and LSMO layer thickness, micromagnet shape, and temperature. In LSFO thin films, shape anisotropy gains importance only in micromagnets where at least one extended edge is aligned parallel to an AFM easy axis. In contrast, in the limit of ultrathin LSFO layers in the LSMO/LSFO superlattice, shape anisotropy effects dominate such that the AFM spin axes at micromagnet edges can be aligned along any in-plane crystallographic direction

Noise-induced front motion: Signature of a global bifurcation

We show that front motion can be induced by noise in a spatially extended excitable system with a global constraint. Our model system is a semiconductor superlattice exhibiting complex dynamics of electron accumulation and depletion fronts. The presence of noise induces a global change in the dynamics of the system forcing stationary fronts to move through the entire device. We demonstrate the effect of coherence resonance in our model; i.e., there is an optimal level of noise at which the regularity of front motion is enhanced. Physical insight is provided by relating the space-time dynamics of the fronts with a phase-space analysis

Management of Acute Myeloid Leukemia: Current Treatment Options and Future Perspectives

Simple Summary AML is a genetically heterogeneous disease with a median age of diagnosis between 60 and 70 years. Thus, many AML patients are not eligible for intensive chemotherapy. Often, the disease is accompanied by a poor prognosis due to high-risk genetic features or due to antecedent hematologic disorders (e.g., myelodysplastic syndrome). Therefore, AML treatment remains a challenge; even after intensive chemotherapy and allogeneic stem cell transplantation (alloHSCT), AML relapses are regularly observed. Thus, new concepts of AML therapy, considering tailored treatment approaches after comprehensive molecular diagnostic or implementing new immunotherapeutic strategies, are urgently needed. This review provides a detailed overview of recent developments and current promising concepts to improve the treatment and the outcome of AML patients. Abstract Treatment of acute myeloid leukemia (AML) has improved in recent years and several new therapeutic options have been approved. Most of them include mutation-specific approaches (e.g., gilteritinib for AML patients with activating FLT3 mutations), or are restricted to such defined AML subgroups, such as AML-MRC (AML with myeloid-related changes) or therapy-related AML (CPX-351). With this review, we aim to present a comprehensive overview of current AML therapy according to the evolved spectrum of recently approved treatment strategies. We address several aspects of combined epigenetic therapy with the BCL-2 inhibitor venetoclax and provide insight into mechanisms of resistance towards venetoclax-based regimens, and how primary or secondary resistance might be circumvented. Furthermore, a detailed overview on the current status of AML immunotherapy, describing promising concepts, is provided. This review focuses on clinically important aspects of current and future concepts of AML treatment, but will also present the molecular background of distinct targeted therapies, to understand the development and challenges of clinical trials ongoing in AML patients

Looking in the Heads of Experienced Teachers – Do they use the Wide Range of Principles of Effective Teaching when Analysing Lessons?

This study aimed to examine whether principles of effective teaching constitute essential criteria for a systematic and successful analysis of lessons. After watching a video of a complete lesson, the participants (each of nine experienced and pre-service teachers) were asked to analyse this lesson in terms of effectiveness for pupils’ learning in the form of an open dialogue. Their comments were analysed by means of a qualitative content analysis and revealed that the experienced teachers independently used the wide range of principles of effective teaching and differed significantly from the pre-service teachers in this regard. Particularly striking were the large differences in the activation of knowledge about these five principles: goal orientation, relating cognitive activities to prior knowledge, classroom climate/learning atmosphere, clarity, and using appropriate examples. These differences point to specific development tasks, in order to improve the analytical skills of student teachers within teacher education

Periodic chiral magnetic domains in single-crystal nickel nanowires

We report on experimental and computational investigations of the domain structure of ~0.2 x 0.2 x 8 {\mu}m single-crystal Ni nanowires (NWs). The Ni NWs were grown by a thermal chemical vapor deposition technique that results in highly-oriented single-crystal structures on amorphous SiOx coated Si substrates. Magnetoresistance measurements of the Ni NWs suggest the average magnetization points largely off the NW long axis at zero field. X-ray photoemission electron microscopy images show a well-defined periodic magnetization pattern along the surface of the nanowires with a period of {\lambda} = 250 nm. Finite element micromagnetic simulations reveal that an oscillatory magnetization configuration with a period closely matching experimental observation ({\lambda} = 240 nm) is obtainable at remanence. This magnetization configuration involves a periodic array of alternating chirality vortex domains distributed along the length of the NW. Vortex formation is attributable to the cubic anisotropy of the single crystal Ni NW system and its reduced structural dimensions. The periodic alternating chirality vortex state is a topologically protected metastable state, analogous to an array of 360{\deg} domain walls in a thin strip. Simulations show that other remanent states are also possible, depending on the field history. Effects of material properties and strain on the vortex pattern are investigated. It is shown that at reduced cubic anisotropy vortices are no longer stable, while negative uniaxial anisotropy and magnetoelastic effects in the presence of compressive biaxial strain contribute to vortex formation.Comment: 15 pages, 11 figure

Fouling pathways in emulsion polymerization differentiated with a quartz crystal microbalance (QCM) integrated into the reactor wall

Emulsion polymerization fouling at hot interfaces is studied in situ, making use of a quartz crystal microbalance with dissipation monitoring (QCM-D). The resonator crystal is heated with a ring-shaped thermal pad from the back, turning it into a plate with elevated temperature. Configured to be one of the walls of a small reactor for emulsion polymerization, this resonator is prone to heat-transfer fouling, similar to regular heated parts of process equipment. The fouling kinetics is readily quantified with this QCM. During polymerization at constant temperature (80 °C), some deposition is always observed. However, a film with a thickness of less than 1 μm (determined gravimetrically with the QCM) is sometimes found, which stabilizes the surface against the deposition of much thicker layers. When reaction fouling proceeds directly to thick deposits, a small increase in resonance bandwidth often occurs a few minutes prior to the main transition, presumably caused by coagulum formed in the bulk making first contact with the surface. Furthermore, particle fouling is studied with temperature ramps on nonreactive dispersions. Fouling, if present, is readily observed

Modulation of FLT3-ITD Localization and Targeting of Distinct Downstream Signaling Pathways as Potential Strategies to Overcome FLT3-Inhibitor Resistance

OBJECTIVES: Internal tandem duplications (ITDs) of the Fms-like tyrosine kinase 3 (FLT3) represent the most frequent molecular aberrations in acute myeloid leukemia (AML) and are associated with an inferior prognosis. The pattern of downstream activation by this constitutively activated receptor tyrosine kinase is influenced by the localization of FLT3-ITD depending on its glycosylation status. Different pharmacological approaches can affect FLT3-ITD-driven oncogenic pathways by the modulation of FLT3-ITD localization. AIMS: The objective of this study was to investigate the effects of N-glycosylation inhibitors (tunicamycin or 2-deoxy-D-glucose) or the histone deacetylase inhibitor valproic acid (VPA) on FLT3-ITD localization and downstream activity. We sought to determine the potential differences between the distinct FLT3-ITD variants, particularly concerning their susceptibility towards combined treatment by addressing either N-glycosylation and the heat shock protein 90 (HSP90) by 17-AAG, or by targeting the PI3K/AKT/mTOR pathway by rapamycin after treatment with VPA. METHODS: Murine Ba/F3 leukemia cell lines were stably transfected with distinct FLT3-ITD variants resulting in IL3-independent growth. These Ba/F3 FLT3-ITD cell lines or FLT3-ITD-expressing human MOLM13 cells were exposed to tunicamycin, 2-deoxy-D-glucose or VPA, and 17-AAG or rapamycin, and characterized in terms of downstream signaling by immunoblotting. FLT3 surface expression, apoptosis, and metabolic activity were analyzed by flow cytometry or an MTS assay. Proteome analysis by liquid chromatography–tandem mass spectrometry was performed to assess differential protein expression. RESULTS: The susceptibility of FLT3-ITD-expressing cells to 17-AAG after pre-treatment with tunicamycin or 2-deoxy-D-glucose was demonstrated. Importantly, in Ba/F3 cells that were stably expressing distinct FLT3-ITD variants that were located either in the juxtamembrane domain (JMD) or in the tyrosine kinase 1 domain (TKD1), response to the sequential treatments with tunicamycin and 17-AAG varied between individual FLT3-ITD motifs without dependence on the localization of the ITD. In all of the FLT3-ITD cell lines that were investigated, incubation with tunicamycin was accompanied by intracellular retention of FLT3-ITD due to the inhibition of glycosylation. In contrast, treatment of Ba/F3-FLT3-ITD cells with VPA was associated with a significant increase of FLT3-ITD surface expression depending on FLT3 protein synthesis. The allocation of FLT3 to different cellular compartments that was induced by tunicamycin, 2-deoxy-D-glucose, or VPA resulted in the activation of distinct downstream signaling pathways. Whole proteome analyses of Ba/F3 FLT3-ITD cells revealed up-regulation of the relevant chaperone proteins (e.g., calreticulin, calnexin, HSP90beta1) that are directly involved in the stabilization of FLT3-ITD or in its retention in the ER compartment. CONCLUSION: The allocation of FLT3-ITD to different cellular compartments and targeting distinct downstream signaling pathways by combined treatment with N-glycosylation and HSP90 inhibitors or VPA and rapamycin might represent new therapeutic strategies to overcome resistance towards tyrosine kinase inhibitors in FLT3-ITD-positive AML. The treatment approaches addressing N-glycosylation of FLT3-ITD appear to depend on patient-specific FLT3-ITD sequences, potentially affecting the efficacy of such pharmacological strategies

Patterning-Induced Ferromagnetism of Fe3GeTe2 van der Waals Materials beyond Room Temperature.

Magnetic van der Waals (vdW) materials have emerged as promising candidates for spintronics applications, especially after the recent discovery of intrinsic ferromagnetism in monolayer vdW materials. There has been a critical need for tunable ferromagnetic vdW materials beyond room temperature. Here, we report a real-space imaging study of itinerant ferromagnet Fe3GeTe2 and the enhancement of its Curie temperature well above ambient temperature. We find that the magnetic long-range order in Fe3GeTe2 is characterized by an unconventional out-of-plane stripe-domain phase. In Fe3GeTe2 microstructures patterned by a focused ion beam, the out-of-plane stripe domain phase undergoes a surprising transition at 230 K to an in-plane vortex phase that persists beyond room temperature. The discovery of tunable ferromagnetism in Fe3GeTe2 materials opens up vast opportunities for utilizing vdW magnets in room-temperature spintronics devices

Building a Data Warehouse for Twitter Stream Exploration

In the recent year Twitter has evolved into an extremely popular social network and has revolutionized the ways of interacting and exchanging information on the Internet. By making its public stream available through a set of APIs Twitter has triggered a wave of research initiatives aimed at analysis and knowledge discovery from the data about its users and their messaging activities. While most of the projects and tools are tailored towards solving specific tasks, we pursue a goal of providing an application in dependent and universal analytical platform for supporting any kind of analysis and knowledge discovery. We employ the well established data warehousing technology with its underlying multidimensional data model, ETL routine for loading and consolidating data from different sources, OLAP functionality for exploring the data and data mining tools for more sophisticated analysis. In this work we describe the process of transforming the original stream into a set of related multidimensional cubes and demonstrate how the resulting data warehouse can be used for solving a variety of analytical tasks. We expect our proposed approach to be applicable for analyzing the data of other social networks as well