Effekte von Eisenchelatoren auf den mTOR-Signalweg in myeloischen Leukämiezellen

In den letzen Jahren konnte gezeigt werden, dass der mTOR Signalweg eine wichtige Rolle in der Regulation der Zellproliferation und des Zellwachstums einnimmt. Des Weiteren stellte sich heraus, dass dieser Signalweg durch den Eisenchelator Deferasirox in myeloischen Leukämiezellen unterdrückt wird. In der vorliegenden Arbeit konnte gezeigt werden, dass ausschließlich Deferasirox im Vergleich zu zwei weiteren Eisenchelatoren einen antiproliferativen und proapoptotischen Effekt auf myeloische Leukämiezellen ausübt. Weiterhin wurde untersucht, ob der mTOR Signalweg einen möglichen Angriffspunkt für die antiproliferative und apoptotische Wirkung von Deferasirox darstellt

Eosinophilie und Exanthem unter lenalidomidhaltiger Therapie beim Multiplen Myelom: Korrelation mit Ansprechen und Survival - eine retrospektive Studie

Das Multiple Myelom(MM) gehört zum Formenkreis der B-Zell Lymphome und zeichnet sich durch eine signifikante Vermehrung monoklonaler Plasmazellen im Knochenmark aus. Durch die Verschiebung der natürlichen Hämatopoese und die Beeinträchtigung des physiologischen Knochengerüsts resultiert eine vielgestaltige Klinik. Bis heute gilt die Erkrankung als unheilbar. Die Zulassung neuartiger Arzneimittlel, wie u.a. der immunmodulatorischen Substanz Lenalidomid, und der Evaluation diverser Therapieregime innerhalb klinischer Phase-III-Studien, trugen dazu bei, dass sich die Prognose betroffener Patienten in den letzten Jahrzehnten sukzessive verbessern konnte. Ziel dieser retrospektiven Studie war es, einen Zusammenhang zwischen dem Auftreten einer Eosinophilie bzw. eines Exanthems unter lenalidomidhaltiger Therapie bei MM Patienten mit Blick auf das Ansprechen bzw. das Gesamtüberleben zu analysieren. Im Analysezeitraum 2007-2013 konnten hierfür insgesamt 206 MM-Patienten, die sich unter lenalidomidhaltiger Therapie am UKT befunden hatten, in die Studie eingeschlossen werden. Im gesamten Zeitraum der medikamentösen Therapie traten bei 11,4% der Patienten ein Exanthem und bei 51% der Patienten eine Eosiophilie auf. Ein prognostischer Zusammenhang zwischen der Höhe der Eosinophilie und dem Therapieansprechen konnte letzlich nicht gesehen werden

The Impact of Patchy Reionization on Ultra-faint Dwarf Galaxies

We investigate how patchy reionization affects the star formation history (SFH) and stellar metallicity of ultra-faint dwarf galaxies (UFDs). Patchy reionization refers to varying ultraviolet (UV) background strengths depending on a galaxy's environment. Recent observations highlight the significance of this effect on UFDs, as UFDs can have different SFHs depending on their relative position with respect to their host halo during the period of reionization. However, most cosmological hydrodynamic simulations do not consider environmental factors such as patchy reionization, and the effect of reionization is typically applied homogeneously. Using a novel approach to implement patchy reionization, we show how SFHs of simulated UFDs can change. Our cosmological hydrodynamic zoom-in simulations focus on UFD analogs with M_vir~10^9solar mass, M_star < 10^5 solar mass at $z=0$. We find that patchy reionization can weaken the effect of reionization by two orders of magnitude up to $z=3$, enabling late star formation in half of the simulated UFDs, with quenching times $\sim$460 Myr later than those with homogeneous reionization. We also show that halo merger and mass assembly can affect the SFHs of simulated UFDs, in addition to patchy reionization. The average stellar iron-to-hydrogen ratio, [Fe/H], of the simulated UFDs with patchy reionization increases by 0.22-0.42 dex. Finally, our findings suggest that patchy reionization could be responsible for the extended SFHs of Magellanic UFDs compared to non-Magellanic UFDs.Comment: 27 pages, 16 figures, Accepted for publication in Astrophysical Journa

Inhomogeneous Galactic Chemical Evolution: Modelling Ultra-Faint Dwarf Galaxies of the Large Magellanic Cloud

Ultra-faint dwarf galaxies are among the oldest and most metal-poor galaxies in the cosmos, observed to contain no gas and a high dark matter mass fraction. Understanding the chemical abundance dispersion in such extreme environments could shed light on the very first generations of stars. We present a novel inhomogeneous chemical evolution model, {\tt i-GEtool}, that we apply to two ultra-faint dwarf galaxies, Carina II and Reticulum II, both satellites of the Large Magellanic Cloud. Our model is based on the Monte Carlo sampling of the initial mass function as star formation proceeds in different gas cells of the galaxy volume. We account for the chemical enrichment of Supernova bubbles as they spread in the interstellar medium, causing dispersion in the elemental abundances. We recreate the abundance patterns of $\alpha$- and odd-$\textit{Z}$ elements, predicting two sequences in [C/Fe] and [N/Fe] at all metallicities. Our models underestimate [C/Fe] and [Ti/Fe] because of the large uncertainty in the adopted stellar nucleosynthesis yields. We discuss that the observed C and N abundances had likely been affected by internal mixing processes, which changed the initial surface abundances in the red giants. Our Supernova feedback scheme is responsible for driving galactic outflows, which quench the star formation activity at early times. We predict an average outflow mass-loading factor $\approx 10^{3}$, which extrapolates towards very low galaxy stellar masses the trend observed at high masses. Finally, by combining our model with the MIST isochrone database, we compare our synthetic colour-magnitude diagrams to observations.Comment: 19 Pages, 12 Figures, 1 Table, Accepted to MNRA

Opening the black box of energy modelling: Strategies and lessons learned

The global energy system is undergoing a major transition, and in energy planning and decision-making across governments, industry and academia, models play a crucial role. Because of their policy relevance and contested nature, the transparency and open availability of energy models and data are of particular importance. Here we provide a practical how-to guide based on the collective experience of members of the Open Energy Modelling Initiative (Openmod). We discuss key steps to consider when opening code and data, including determining intellectual property ownership, choosing a licence and appropriate modelling languages, distributing code and data, and providing support and building communities. After illustrating these decisions with examples and lessons learned from the community, we conclude that even though individual researchers' choices are important, institutional changes are still also necessary for more openness and transparency in energy research

Star Formation Histories of Ultra-faint Dwarf Galaxies: Environmental Differences between Magellanic and Non-Magellanic Satellites?*

We present the color–magnitude diagrams and star formation histories (SFHs) of seven ultra-faint dwarf galaxies: Horologium 1, Hydra 2, Phoenix 2, Reticulum 2, Sagittarius 2, Triangulum 2, and Tucana 2, derived from highprecision Hubble Space Telescope photometry. We find that the SFH of each galaxy is consistent with them having created at least 80% of the stellar mass by z ∼ 6. For all galaxies, we find quenching times older than 11.5 Gyr ago, compatible with the scenario in which reionization suppresses the star formation of small dark matter halos. However, our analysis also reveals some differences in the SFHs of candidate Magellanic Cloud satellites, i.e., galaxies that are likely satellites of the Large Magellanic Cloud and that entered the Milky Way potential only recently. Indeed, Magellanic satellites show quenching times about 600 Myr more recent with respect to those of other Milky Way satellites, on average, even though the respective timings are still compatible within the errors. This finding is consistent with theoretical models that suggest that satellites’ SFHs may depend on their host environment at early times, although we caution that within the error bars all galaxies in our sample are consistent with being quenched at a single epoch

The Fourteenth Data Release of the Sloan Digital Sky Survey: First Spectroscopic Data from the extended Baryon Oscillation Spectroscopic Survey and from the second phase of the Apache Point Observatory Galactic Evolution Experiment

The fourth generation of the Sloan Digital Sky Survey (SDSS-IV) has been in operation since July 2014. This paper describes the second data release from this phase, and the fourteenth from SDSS overall (making this, Data Release Fourteen or DR14). This release makes public data taken by SDSS-IV in its first two years of operation (July 2014-2016). Like all previous SDSS releases, DR14 is cumulative, including the most recent reductions and calibrations of all data taken by SDSS since the first phase began operations in 2000. New in DR14 is the first public release of data from the extended Baryon Oscillation Spectroscopic Survey (eBOSS); the first data from the second phase of the Apache Point Observatory (APO) Galactic Evolution Experiment (APOGEE-2), including stellar parameter estimates from an innovative data driven machine learning algorithm known as "The Cannon"; and almost twice as many data cubes from the Mapping Nearby Galaxies at APO (MaNGA) survey as were in the previous release (N = 2812 in total). This paper describes the location and format of the publicly available data from SDSS-IV surveys. We provide references to the important technical papers describing how these data have been taken (both targeting and observation details) and processed for scientific use. The SDSS website (www.sdss.org) has been updated for this release, and provides links to data downloads, as well as tutorials and examples of data use. SDSS-IV is planning to continue to collect astronomical data until 2020, and will be followed by SDSS-V.Comment: SDSS-IV collaboration alphabetical author data release paper. DR14 happened on 31st July 2017. 19 pages, 5 figures. Accepted by ApJS on 28th Nov 2017 (this is the "post-print" and "post-proofs" version; minor corrections only from v1, and most of errors found in proofs corrected

Electricity Market Design 2030-2050: Moving Towards Implementation

Climate change and ambitious emission-reduction targets call for an extensive decarbonization of electricity systems, with increasing levels of Renewable Energy Sources (RES) and demand flexibility to balance the variable and intermittent electricity supply. A successful energy transition will lead to an economically and ecologically sustainable future with an affordable, reliable, and carbon-neutral supply of electricity. In order to achieve these objectives, a consistent and enabling market design is required. The Kopernikus Project SynErgie investigates how demand flexibility of the German industry can be leveraged and how a future-proof electricity market design should be organized, with more than 80 project partners from academia, industry, governmental and non-governmental organizations, energy suppliers, and network operators. In our SynErgie Whitepaper Electricity Spot Market Design 2030-2050 [1], we argued for a transition towards Locational Marginal Prices (LMPs) (aka. nodal prices) in Germany in a single step as a core element of a sustainable German energy policy. We motivated a well-designed transition towards LMPs, discussed various challenges, and provided a new perspective on electricity market design in terms of technological opportunities, bid languages, and strategic implications. This second SynErgie Whitepaper Electricity Market Design 2030-2050: Moving Towards Implementation aims at further concretizing the future German market design and provides first guidelines for an implementation of LMPs in Germany. Numerical studies –while not being free of abstractions –give evidence that LMPs generate efficient locational price signals and contribute to manage the complex coordination challenge in (long-term) electricity markets, ultimately reducing price differences between nodes. Spot and derivatives markets require adjustments in order to enable an efficient dispatch and price discovery, while maintaining high liquidity and low transaction costs. Moreover, a successful LMP implementation requires an integration into European market coupling and appropriate interfaces for distribution grids as well as sector coupling. Strategic implications with regard to long-term investments need to be considered, along with mechanisms to support RES investments. As a facilitator for an LMP system, digital technologies should be considered jointly with the market design transition under an enabling regulatory framework. Additional policies can address distributional effects of an LMP system and further prevent market power abuse. Overall, we argue for a well-designed electricity spot market with LMPs, composed of various auctions at different time frames, delivering an efficient market clearing, considering grid constraints, co-optimizing ancillary services, and providing locational prices according to a carefully designed pricing scheme. The spot market is tightly integrated with liquid and accessible derivatives markets, embedded into European market coupling mechanisms, and allows for functional interfaces to distribution systems and other energy sectors. Long-term resource adequacy is ensured and existing RES policies transition properly to the new market design. Mechanisms to mitigate market power and distributional effects are in place and the market design leverages the potential of modern information technologies. Arapid expansion of wind andsolar capacity will be needed to decarbonize the integrated energy system but will most likely also increase the scarcity of the infrastructure. Therefore, an efficient use of the resource "grid" will be a key factor of a successful energy transition. The implementation of an LMPs system of prices with finer space and time granularity promises many upsides and can be a cornerstone for a futureproof electricity system, economic competitiveness, and a decarbonized economy and society. Among the upsides, demand response (and other market participants with opportunity costs) can be efficiently and coherently incentivized to address network constraints, a task zonal systems with redispatch fail at. The transition to LMPs requires a thorough consideration of all the details and specifications involved in the new market design. With this whitepaper, we provide relevant perspectives and first practical guidelines for this crucial milestone of the energy transition

Electricity Spot Market Design 2030-2050

Driven by the climate conference in Paris in December 2015 countries worldwide are confronted with the question of how to shape their power system and how to establish alternative technologies to reduce harmful CO2 emissions. The German government plans that even before the year 2050, all electricity generated and consumed in Germany should be greenhouse gas neutral [1]. To successfully integrate renewable energies, a future energy system must be able to handle the intermittent nature of renewable energy sources such as wind and solar. One important means to address such electricity production variability is demand-side flexibility. Here, industry plays a major role in responding to variable electricity supply with adequate flexibility. This is where the Kopernikus project SynErgie comes in with more than 80 project partners from academia, industry, governmental, and non-governmental organizations as well as energy suppliers and network operators. The Kopernikus project SynErgie investigates how to best leverage demand-side flexibility in the German industry. The current electricity market design in Germany is not well suited to deal with increasing levels of renewable energy, and it does not embrace demand-side flexibility. Almost 6GW of curtailed power in 2019 provide evidence that changes are needed with respect to the rules governing electricity markets. These rules were designed at a time when electricity generation was concentrated on a few large and dispatchable conventional power plants and demand was considered inelastic. The SynErgie Cluster IV investigates how a future-proof electricity market design should be organized. The corresponding Work Package IV.3.1 more specifically deals with analyzing and designing allocation and pricing rules on electricity spot markets. The resulting design must be well suited to accommodate demand-side flexibility and address the intermittent nature of important renewable energy sources. This whitepaper is the result of a fruitful collaboration among the partners involved in SynErgie Cluster IV which include Germany’s leading research organizations and practitioners in the field. The collaboration led to an expert workshop in October 2020 with participation from a number of international energy market experts such as Mette Bjørndal (NHH), Endre Bjørndal (NHH), Peter Cramton (University of Maryland and University of Cologne), and Raphael Heffron (University of Dundee). The whitepaper details the key recommendations from this workshop. In particular, the whitepaper recommends a move to a locational, marginal price-based system together with new bidding formats allowing to better express flexibility. We argue in favor of a one-step introduction of locational, marginal prices instead of repeatedly splitting existing zones. Frequent zone splitting involves recurring political debates as well as short- and long-run instabilities affecting the basis for financial contracts, for example. Importantly, the definition of stable prize zones is very challenging with increasing levels of distributed and renewable energy sources. The recommendation is the outcome of an intense debate about advantages and downsides of different policy alternatives. However, such a transition to locational, marginal prices is not without challenges, and it is a call to arms for the research community, policymakers, and practitioners to develop concepts on how to best facilitate the transition and ensure a reliable and efficient electricity market of the future