Matrix completion is an essential problem in modern machine learning, as it is e.g. important for the calibration of the recommendation systems. We consider the problem of matrix completion in the setting where the learner can choose where to sample. In this setting, it can be of interest to target more specifically parts of the matrix where it is discovered that the complexity is high (higher local rank), where the knowledge is limited (few sampled points), or where the noise is high. This project plans to consider first the problem of active learning for matrix completion when the matrix can be subdivided into block submatrices of small ranks that are known, and then in the more general case where this cannot be done.

Currently, database systems face two big challenges: First, the application scenarios become more and more diverse ranging from purely relational to graph-shaped or stream-based data analysis. Second, the hardware landscape becomes more and more heterogeneous with standard multi-core Central Processing Units (CPUs) as well as specialized high-performance co-processors such as Graphics Processing Unit (GPUs) or Field Programmable Gate Arrays (FPGAs).
Recent research shows that operators designed for co-processors can outperform their CPU counterparts. However, most of the approaches focus on single-device processing to speedup single analyses not considering overall system performance. Consequently, they miss hidden performance potentials of parallel processing across all devices available in the system. Furthermore, current research results are hard to generalize and, thus, cannot be applied to other domains and devices.
In this project, we aim to provide integration concepts for diverse operators and heterogeneous hardware devices in adaptive database systems. We work on optimization strategies not only exploiting individual device-specific features but also the inherent cross-device parallelism in multi-device systems. Thereby we focus on operators from the relational and graph domain to derive concepts not limited to a certain application domain. To achieve the project goals, interfaces and abstraction concepts for operators and processing devices have to be defined. Furthermore, operator and device characteristics have to be made available to all system layers such that the software layer can account for device specific features and the hardware layer can adapt to the characteristics of the operators and data. The availability of device and operator characteristics is especially important for global query optimization to find a suitable execution strategy. Therefore, we also need to analyze the design space for query processing on heterogeneous hardware, in particular with regards to functional, data and cross-device parallelism. To handle the enormous complexity of the query optimization design space incurred by the parallelism, we follow a distributed optimization approach where optimization tasks are delegated to the lowest possible system layer. Lower layers also have a more precise view on device-specific features allowing to exploit them more efficiently. To avoid interferences of optimization decisions at different layers, a focus is also set on cross-layer optimizations strategies. These will incorporate learning-based techniques for evaluating optimization decisions at runtime to improve future optimization decisions. Moreover, we expect that learning-based strategies are best suited to integrate device-specific features not accounted for by the initial system design, such as it is often the case with the dynamic partial reconfiguration capabilities of FPGAs.

The ADAP-SKAP55 proteins form a molecular complex that regulates adhesion and migration of T cells. Our findings from the 2nd funding period suggest a role of the two proteins in modulating membrane scaffolding and actin filament organization. We now plan to delineate their contribution to actin-mediated migration of T cells by structural, biochemical and molecular biology techniques. We will exploit our mechanistic insights to probe in mice the role of ADAP-SKAP55 as well as their interaction partners in stress-induced T cell extravasation into the brain meningeal space and clarify their relevance for T cell-supported cognitive functioning and coping with traumatic stress.

Currently, database systems face two big challenges: First, the application scenarios become more and more diverse ranging from purely relational to graph-shaped or stream-based data analysis. Second, the hardware landscape becomes more and more heterogeneous with standard multi-core Central Processing Units (CPUs) as well as specialized high-performance co-processors such as Graphics Processing Unit (GPUs) or Field Programmable Gate Arrays (FPGAs).
Recent research shows that operators designed for co-processors can outperform their CPU counterparts. However, most of the approaches focus on single-device processing to speedup single analyses not considering overall system performance. Consequently, they miss hidden performance potentials of parallel processing across all devices available in the system. Furthermore, current research results are hard to generalize and, thus, cannot be applied to other domains and devices.
In this project, we aim to provide integration concepts for diverse operators and heterogeneous hardware devices in adaptive database systems. We work on optimization strategies not only exploiting individual device-specific features but also the inherent cross-device parallelism in multi-device systems. Thereby we focus on operators from the relational and graph domain to derive concepts not limited to a certain application domain. To achieve the project goals, interfaces and abstraction concepts for operators and processing devices have to be defined. Furthermore, operator and device characteristics have to be made available to all system layers such that the software layer can account for device specific features and the hardware layer can adapt to the characteristics of the operators and data. The availability of device and operator characteristics is especially important for global query optimization to find a suitable execution strategy. Therefore, we also need to analyze the design space for query processing on heterogeneous hardware, in particular with regards to functional, data and cross-device parallelism. To handle the enormous complexity of the query optimization design space incurred by the parallelism, we follow a distributed optimization approach where optimization tasks are delegated to the lowest possible system layer. Lower layers also have a more precise view on device-specific features allowing to exploit them more efficiently. To avoid interferences of optimization decisions at different layers, a focus is also set on cross-layer optimizations strategies. These will incorporate learning-based techniques for evaluating optimization decisions at runtime to improve future optimization decisions. Moreover, we expect that learning-based strategies are best suited to integrate device-specific features not accounted for by the initial system design, such as it is often the case with the dynamic partial reconfiguration capabilities of FPGAs.

In the frame of the research project it is planned to analyse the fundamentals and to derive models for the collision of droplets with larger solid particles and their coating for Euler/Lagrange calculations. The elementary process of collisions between droplets and larger solid particles will be analysed experimentally using imaging techniques. For that purpose a droplet chain will be produced into which solid particles are shot with defined velocity and frequency. As a result of the collision of droplets with larger particles one may observe bouncing, deposition or disintegration. The collision event will be visualised using high-speed cameras and illumination by LED-arrays and a laser. The results will be analysed by image processing.
For all the relevant parameters of influence it is first required to determine the outcome of the collision and summarise them with respect to the important non-dimensional numbers, e.g. Ohnesorge-number and impact Reynolds-number. The considered parameters of influence are the size ratio (droplet/particle), droplet liquid properties (viscosity and surface tension), particle properties (temperature and surface roughness), impact velocity and impact location of the droplet on the particle surface (i.e. central and lateral impacts). As mentioned before, the droplets are smaller than the particles and the liquid is wetting. All these effects need to be considered for deriving physically-based boundaries between the collision outcomes using the relevant non-dimensional numbers. For the regime splashing or partial deposition the size distribution of the droplet fragments also will be analysed and modelled.
The next step is the experimental determination of the dimensions of the final liquid film on the particles, including film thickness and lateral dimension of the film. For that purpose the droplet liquid will be doped with fluorescing dye in order to allow a better distinction from the image of the particle. For the development of the coating model with respect to the impact conditions and the relevant non-dimensional numbers, physically based correlations shall be developed.
In addition, for analyzing the collision outcomes, theoretical studies will be conducted based on an energy balance. The liquid film formation on the particle will be studied based on film theory.
The developed coating model, which considers a broad range of parameters and also for the first time lateral impact, will be derived for being used in the frame of Lagrangian calculations of technical coating processes.

Atomic layer deposition processes for phosphorus-containing layers will be developed and investigated. Recently developed ALD processes for boron oxide and antimony oxide will be further improved and analyzed as well. These layers will be used as a dopant sources for silicon doping to produce ultra-shallow and homogeneous doped pn junctions, especially for applications, where doping on three-dimensional surface configurations is required.
In addition, suitable methods for stabilization of unstable dopant layers need to be found and analyzed. The deposited layers will be characterized and the diffusion processes in the silicon and in the oxide phase will be studied, and thus the doping processes will be modeled.

Meningiomas are frequent intracranial tumours, in which a significant proportion of patients may benefit from pharmacological treatment in addition to surgery and irradiation, especially in aggressive meningioma subtypes. However, so far no treatment scheme has been proven to be effective. Our group has recently demonstrated in vitro and in vivo that mTORC1 inhibitors represent an effective meningioma treatment option.
The role of genetic factors for biologic aggressiveness and chemosensitivity of meningiomas is not well defined. This applies even to the tumour suppressor NF2 (merlin), despite the high frequency of functional losses of this gene. Recently, the oncogenic mutation E17K in the AKT1 gene (AKT1E17K), which leads to a constitutive activation of this kinase, has been identified as a somatic mutation in a fraction of meningiomas without NF2 loss, suggesting an independent AKT1-driven tumor-promoting pathway. This constitutive activation of AKT1 is highly interesting, because AKT1 interacts bidirectionally with two mTOR-complexes and can be expected to modify mTOR-associated growth regulation and chemosensitivity.
In this project, we intend to analyze a) the role of AKT1E17K for the regulation of mTOR-complexes and mTOR-dependent features of meningioma cells, i.e. proliferation, adhesion, migration, invasion, colony formation and chemosensitivity in vitro, b) in mouse models the impact of AKT1E17K for tumorigenicity and growth kinetics of malignant meningiomas in tumor-bearing mice, and c) the response of the latter parameters in vivo towards inhibitors of mTOR-complex 1, dual inhibitors of mTORC1/2 or inhibitors of AKT1, which affect also the mutant form of the enzyme. The in vitro studies will be based upon syngeneic cell lines expressing mutated and wild type AKT1. In vivo experiments will include intracranial xenografts of human tumor cells and genetically induced mouse meningioma models. The genetic mouse model for meningeal expression of AKT1E17K requires crossing of meningeal Cre-driver mice (PTGDS-Cre or PTGDS-Cre-ERT2) with Rosa26-AktE17K mice, the latter containing a AKT1E17K-transgene, separated by a floxed stop-signal (LSL) from its promoter, thereby allowing Cre-dependent meningeal expression of the mutant Akt enzyme.

Sensitization of lanthanide-based phosphors by transition metals for high-brightness tunable thermometers. (SensiTherm)The main objective of this project is to enhance the photoluminescence properties of lanthanide-based optical thermometers via sensitization by transition metal ions. Taking advantage of the significantly higher absorption cross section of transition metal ions, the emission intensity of the lanthanide ions can be significantly enhanced, which will increase the signal levels offered by the thermometers. In addition, because the energy transfer from sensitizer to activator is strongly temperature-dependent, the sensitization of lanthanide emissions through transition metal ions will open a new path to enhance the temperature sensitivity of co-doped luminescent thermometers. To achieve this goal a detailed understanding of the sensitization process of lanthanides by transition metal ions in microcrystalline particles will be developed. ´The influence of material parameters such as local crystal field, phonon energy, dopant concentration, and energy level difference between excited states of activator and sensitizers on the temperature-dependent sensitization process enables control and intentional design of luminescent thermometers with high emission intensity and high sensitivity to temperature changes. To investigate the energy transfer, microcrystalline samples will be synthesized in Wroclaw, and the spectroscopic properties will be investigated in Magdeburg using dispersed particle methods and quantum yield measurements to unambiguously quantify the absorption, energy transfer and emission processes. Host, sensitizer and activator dependent parameters will be investigated by systematically probing combinations of host (perovskites and garnets), transition metal (Cr3+, Mn4+, Ti3+ and V5+) and lanthanides (Eu3+, Dy3+, Ce3+, Pr3+, Tb3+). The absorption cross section, the energy transfer rate, as well as radiative and non-radiative de-excitation rates will be measured, which will also serve as a comparison for theoretical models developed in Wroclaw. Those rates will also be measured over a range of dopant concentrations (sensitizer and activator), excitation power densities and temperatures to investigate the effect of each parameter on the sensitization process. The proposed project brings together the expertise of Wroclaw in the synthesis, structural characterisation and theory of transition metal and lanthanide doped compounds, with that of Magdeburg in advanced spectroscopic techniques based on probing the luminescence of dispersed particles in temperature-controlled fluid flow systems. Implementation of this project will provide an extensive characterization of energy transfer processes between transition metals and lanthanides, for both fundamental understanding as well as to provide luminescence thermometers with enhanced characteristics (more suitable excitation window, higher emission intensity, higher temperature sensitivity) which will greatly contribute to the progress of many fields of science for which temperature is a property of foremost importance.

Database Management Systems (DBMS) face two challenges today. On the one hand DBMS must handle Online Transaction Processing (OLTP), and Online Analytical Processing (OLAP) in combination to enable real-time analysis of business processes. The real-time analysis of business processes is necessary to improve the quality of reports and analyzes, since fresh data is favored for modern analysis rather than historical data only. On the other hand, computer systems become increasingly heterogeneous to provide better hardware performance. The architecture changes from single-core CPUs to multi-core CPUs supported by several co-processors. These trends must be considered in DBMS to improve the quality and performance, and to ensure that DBMS satisfy future requirements (e.g., more complex queries, or more increased data volume). Unfortunately, current research approaches address only one of these two challenges: either the combination of OLTP and OLAP workloads in traditional CPU-based systems, or co-processor acceleration for a single workload type is considered. Therefore, an unified approach addressing both challenges at once is missing. In this project we want to include both challenges of DBMS to enable efficient processing of combined OLTP / OLAP workloads in hybrid CPU / Co-processor systems. This is necessary in order to realize real-time business intelligence. The main challenge is guaranteeing the ACID properties for OLTP, while at the same time to combine and to process efficiently OLTP / OLAP workloads in such a hybrid systems.

The GUFI network was founded at the end of 2013 as DFG-funded Core Facility. The initial project duration was three years. The overall goal of GUFI is to facilitate and harmonize the access to German Ultra High Field (UHF) sites. GUFI has made important contributions to addressing these challenges and has identified several new areas of common interest to all German UHF sites. A number of unprecedented milestones have been achieved in building a national UHF Magnetic Resonance (MR) community including establishment of a common presentation and access portal for all UHF MR sites; initiation of regular QA; consensus on access procedures, implant handling and RF coil testing; and regular structured communication between all UHF sites. In a second funding phase, starting 2017, the following goals will be pursued:

• Establishment of an online platform for MR safety training including examination questions to verify attainment of training goals.
• Continuation and extension of establishment of procedures for safe examinations of subjects with implants. Continuation and refinement of QA activities.
• Formulation and publication of White Papers.
• Annual workshops with participation from all GUFI sites to foster communication.
• Planning of first multicenter UHF trials.
• Maintenance and extension of the online web-based communications platform.
• Coordination activities with other international initiatives such as UK7T and Euro-Bioimaging.
• Preparation of access procedures for the infrastructure to be established at National Biomedical Imaging Facilities in Jülich and Heidelberg that have been applied for as part of the National Roadmap for Research Infrastructures of the German Federal Ministry of Education and Research (BMBF).

During aging many biological and environmental processes contribute to the functional
decline of cells. However, the mechanisms how this aging is reflected on the level of altered
synaptic plasticity is unknown. Interestingly, there is a wide heterogeneity in the pace of
aging in human and animal populations (Foebel, Pedersen, 2016). One factor that likely
contributes to accelerated aging processes is the exposure to adverse environmental events
in early and/or later life (Gassen et al., 2017). There is strong evidence that stress-induced
3 Research Program RTG SynAGE
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Figure 12: A: Heterozygous BDNF knockout animals exhibit an age-dependent deficit in spatial learning. B: The
abundance of signaling-competent TrkB receptors declines with aging. C: BDNF protein expression declines in
different areas with aging.
alterations in BDNF expression contribute to long-lasting cellular and functional alterations in
the hippocampal network (Bath et al., 2013). Stressful events alter spine densities in areas
CA3 and CA1 of the hippocampus (Duman and Duman, 2015) and result in long-lasting
reductions in BDNF protein expression (Lakshminarasimhan and Chattarji, 2012). Since
BDNF is a key mediator of synaptic plasticity and exerts neuroprotective functions, reduced
BDNF levels and subsequently altered activation of downstream signaling molecules (Panja
et al., 2014) might be a key mechanism for accelerated aging of synaptic transmission. We
recently observed a decline of brain BDNF levels and abundance of signaling-competent
flTrkB receptors in aged WT mice (Petzold et al., 2015). In BDNF+/- mice this additional agedependent
decline leads to deficits in hippocampus- and amygdala-dependent learning
processes (Psotta et al., 2013; Endes and Lessmann, 2012; see Figure 12).
However, the mechanisms how BDNF and its downstream signaling molecules are involved
in these processes are widely unknown, thus limiting the exploitation of its possible therapeutic
potential against such aging processes. Identifying altered signaling events and protein
interaction partners downstream of TrkB activation are likely to provide novel approaches to
reverse stress-induced changes that result in accelerated aging.

Fear optimally prepares the brain and body for dangerous situations, which helps humans and animals cope with potentially dangerous events. Dysfunctions within the mechanisms underlying fear can lead to maladaptive fear. Some clinical manifestations of such maladaptive fear are post-traumatic stress disorder or panic disorder. Several clinical studies identified a polymorphism in the neuropeptide S (NPS) receptor gene that is associated with an increased incidence of panic disorder. Moreover, the identified risk allele of the NPS receptor interacts with unfavorable developmental conditions (here: childhood maltreatment). These findings motivated neuroscientists to investigate the role of NPS and its receptors in animal models of normal fear and anxiety. However, there is surprisingly little research on NPS and its receptor in animal models of pathological fear. Such models would be especially suitable to explore gene environment interactions.

Therefore, the aim of the proposed study is to explore the role of NPS and its receptor in animal models of pathological fear. First, the phenotype of transgenic mice with a deficiency of the NPS receptor will be characterized in animal models of post-traumatic stress disorder and panic disorder. Then, the additional effects of developmental conditions (enriched environment, social stress) on the phenotype of wildtype and NPS receptor-deficient animals will be studied. Lastly, we want to test if NPS injections can block the development of pathological fear.
The aim of the proposed study is to increase our understanding of the role of NPS and its receptor in normal and pathological fear. We hope that our data can contribute to the development of pharmacological therapies with NPS receptor agonists.

Infertility, particularly in industrialized countries, cannot longer be considered a personal problem but represents rather a public health issue whose significance arises rapidly. The inability to conceive a child does not only result in personal conflicts but has also been associated with psychological and even psychiatric disorders. Beside intensive costs for infertility treatments there are further costs involved managing mental health complications. For this reason, a detailed understanding of mechanisms underlying each step of a successful pregnancy is essential. Ultimately, this will contribute to therapeutic interventions for couples suffering from undesired childlessness and reduce the number of patients developing mental disorders due to reproductive failure.
One milestone of pregnancy is represented by the adequate implantation of the embryo into the maternal endometrium. Proper embryo implantation is a prerequisite for successful pregnancy progression without placenta-associated complications. However, despite intensive research activity, the mechanisms underlying embryo implantation are far from being understood. Several own and other studies indicate a critical involvement of various hormones and immune cell populations in the implantation process and suggest endocrine-immune interdependencies.
The proposed research project primarily focuses on the participation of regulatory T cells and dendritic cells in embryo implantation. Secondary, it will be clarified whether the pregnancy hormone human chorionic gonadotropin influences both immune cell types in their functionality. In vitro analyses using human and murine implantation models as well as in vivo analyses in transgenic mouse strains will be applied.
Our results will advance the state-of-the-art in the reproductive immunology field by gaining more knowledge about the relevance of the maternal immune systems for a proper embryo implantation process. Based on this knowledge, we hope that our research will build bridges between basic research and clinical application resulting in novel and advanced therapeutic interventions for infertile patients.

Reactions of hydrophobic educts with a water soluble catalyst can be carried out in micellar systems. For an economically acceptable reaction rate and for a fast product separation the operating conditions must be chosen such that a micellar three phase system occurs. The corresponding bi-disperse drop size distributions (DSD) caused by stirring are decisive for both process steps but not characterised up to now. DSD of bi-disperse systems will therefore be determined extending experimental (WG Kraume) and numerical methods (WG Thévenin).

In order to analyze the occurrence and the impact of superstructures on
turbulent mixing in channels at high Reynolds numbers with a parallel injection,
a combination of Direct Numerical Simulation (DNS), vortex
definition and identification, and feature-based visualization, is
proposed. Standard, off-the-shelf solutions are not available for this
purpose.
Concerning DNS, the central issue is to access high Reynolds numbers
with excellent efficiency on HPC systems. Additionally, suitable
models must be included to describe numerically all fluid
properties relevant for mixing.
The main challenge in vortex extraction is three-fold. Firstly,
high-intensity turbulence excludes standard vortex definitions that are
based on a local analysis of the flow derivatives. Instead, global,
Lagrangian, or hierarchical vortex definitions are necessary that are
based on filtering operations on the flow map instead of the velocity
field. Secondly, vortex definitions and parameter tuning has to be
adapted such that it does not focus on upstream vortices
close to injection but tackles the less obvious, noisier
and more unsteady vortex structures downstream. Thirdly, in terms of
visual analysis, the main challenge is associated with the sheer size of
the data sets: DNS typically delivers data sets that cannot be
completely stored during the simulation. Hence, on-the-fly solutions for
the visual analysis are necessary.
To analyze the phenomena, DNS, vortex extraction and visualization have
to be combined into a feedback cycle in a computational steering sense.
While a multi-scale POD along with an automatic vortex extraction is carried out
on-the-fly, the resulting vortices are later visually analyzed in an interactive manner,
allowing adaptation of both the visualization parameters and further simulation
parameters. This efficient combination of DNS, POD, and visual analysis shall allow the identification of superstructures and help explain their impact on transport processes.

In order to analyze the occurrence and the impact of superstructures on turbulent mixing in channels at high Reynolds numbers with a parallel injection, a combination of Direct Numerical Simulation (DNS), vortex definition and identification, and feature-based visualization, is proposed. Standard, off-the-shelf solutions are not available for this purpose. Concerning DNS, the central issue is to access high Reynolds numbers with excellent efficiency on HPC systems. Additionally, suitable models must be included to describe numerically all fluid properties relevant for mixing. The main challenge in vortex extraction is three-fold. Firstly, high-intensity turbulence excludes standard vortex definitions that are based on a local analysis of the flow derivatives. Instead, global, Lagrangian, or hierarchical vortex definitions are necessary that are based on filtering operations on the flow map instead of the velocity field. Secondly, vortex definitions and parameter tuning has to be adapted such that it does not focus on upstream vortices close to injection but tackles the less obvious, noisier and more unsteady vortex structures downstream. Thirdly, in terms of visual analysis, the main challenge is associated with the sheer size of the data sets: DNS typically delivers data sets that cannot be completely stored during the simulation. Hence, on-the-fly solutions for the visual analysis are necessary.

Turbulent flows are inherently 3-dimensional. Over the past decade, the development of Tomographic Particle Image Velocimetry (PIV) has enabled three-dimensional velocity measurements, thereby facilitating tremendous progress in the understanding of turbulent flow structures. In many turbulent heat transfer processes, whether naturally occurring (e.g., natural convection in the ocean, atmosphere or mantle) or induced to improve the efficiency or reliability of devices (e.g., gas turbines and electronic circuits), knowledge of the velocity field alone is insufficient to unambiguously describe the flow, and simultaneous temperature measurements are highly desirable. This project proposes a novel concept for simultaneous three-dimensional temperature and velocity measurements based on combining thermographic phosphor particles with 3-dimensional particle-based velocimetry techniques. Unlike the three-dimensional scalar measurement concept based on tomographic reconstruction of volumetric signals from multiple views, here the temperature of individual micron-size thermographic phosphor particles is probed.

Droplets impacting on soft materials are frequently encountered in everyday life, e.g. water drops on skin during showering, drops impacting on fresh paint or on plant leaves. However, research so far mainly focused on hard surfaces, liquid pools and miscible liquid surface layers. Soft substrates offer an interesting spectrum of new phenomena, e.g. increase of nucleation efficiency during condensation or the possiblity of measuring the small traction forces exterted by cells. The coupled problem of static shapes of a droplet on visco-elastic substrates has been modeled extensively, and comparatively slow processes of contact line motion have been
addressed.

However, there are very few studies of the interaction of soft substrates with rapidly moving contact lines, as e.g. encountered during drop impact. In that case, almost exclusively global side view images were applied, the processes near the three phase contact line
or under the drops have not been studied microscopically.

In this project, I study drop impact and similar processes involving rapid contact line motion on soft visco-elastic gels, viscous liquid layers and more complex adaptive or switchable substrates (obtained in collaborations in the SPP) in order to reveal the connection between the micro- and macro-scale processes related to rapid contact line motion. Side view imaging will be combined with a number of non-standard high-speed bottom view techniques, providing access to the substrate's deformations, strains or contact formation processes of the surface with the liquid.

The project is part of the DFG-priority program SPP2171: Dynamic Wetting of Flexible, Adaptive and Switchable Surfaces.

This project addresses the role of the habenula (Hb) in motivated behaviour of humans. The Hb is an important relay on a major descending pathway from the forebrain to the brain stem with predominantly inhibitory influence on monoaminergic nuclei, thereby controlling release of dopamine and serotonin to the forebrain. The project aims at understanding the contribution of the Hb to active and passive avoidance and to learning from aversive events. This comprises studying habenular activity, its structural and functional embedding in pallido-habenulo-mesencephalo-striatal networks, and its neurochemical interactions. To this end, high-resolution structural, diffusion-weighted and functional MRI, pharmacological challenges, and in-vivo receptor density mapping using positron emission tomography will be performed in healthy volunteers. Understanding habenular functions is important not only for fundamental neurosciences but also for clinical neuropsychiatry, because dysfunction of the Hb has been suggested to contribute to the pathophysiology of psychiatric disorders, such as affective disorders and addiction. Therefore, we will search for volume and connectivity aberrations of the Hb in patients with addiction.

The modeling of phase fields and size effects in solids, such as the width of shear bands or the grain size dependence of the plastic flow in poly-crystals, need to be based on non-standard continuum approaches which incorporate length-scales.
With the ongoing trend of miniaturization and nanotechnology, the predictive modeling of these effects play an increasingly important role.
The mixed multi-field representation of gradient-type problems is a recently introduced thermomechanically consistent framework for modeling such kind of phenomena. The key idea is to extend the field of constitutive state variables by micromechanical independents and further to derive the macro and micro balance equations in a closed form.

DNA binding protein-A (DbpA) belongs to the human cold shock protein superfamily with known functions related to fibrogenesis, cancerogenesis and transcriptional/translational regulation. Evidences link DbpA with an activated, proliferative tubular cell phenotype. Beyond its participation in tight junction-related complex formation, our data suggest mitochondrial and exosomal functions. Furthermore, DbpA protein is actively secreted, e.g. in mesangioproliferative nephritis. The combined effects of two cold shock proteins, Y-box binding protein-1 (YB-1) and DbpA, results in an invasive, pro-migratory cell phenotype. The current proposal focuses on inflammatory kidney diseases (such as unilateral ureteral nephropathy, nephrotoxic nephritis and diabetic nephropathy) and aims to investigate the functional role(s) and participation of DbpA. We will determine (i) functions fulfilled by intra- and extracellular DbpA. For intracellular DbpA its participation in mitochondrial energy homeostasis will be clarified. Furthermore a search for cell surface receptors will be set up that may affect intracellular signaling/cell fate decision. (ii) Having identified an overlap in the interactome of DbpA and YB-1, we will characterize extra- and intracellular interactions of both proteins and relate these to functions. Additionally the contribution of exosomal DbpA to cell proliferation, pro-inflammatory and -fibrotic cell phenotypes will be investigated. (iii) We will clarify how genetic ablation of DbpA affects the inflammatory response/outcome of kidney diseases. (iv) Finally, preliminary data indicate that DbpA expression levels in leukocytes is highly regulated, at the same time serum contains significant protein amounts. Our quest is to determine by which stimuli the DbpA expression is regulated in circulating immune cells. Given autoimmune responses against cold shock proteins are established we will test for autoantibodies against DbpA.

The proposal addresses pivotal questions on the functional role(s) of the cold shock protein DbpA in the pathogenesis of inflammatory kidney diseases. Given the marked cellular effects seen with modification of DbpA expression in mesangial and tubular cells our quest is to harness the findings to develop diagnostic and therapeutic strategies.

The main focus of A6 is a deeper understanding of the interaction between the electronic and the phononic
system that governs the device performance of nitride based nanostructures. Our approach is a unique
combination and correlation of nanoscopic methods like tip-enhanced Raman spectroscopy (TERS), μPhotoluminescence (μPL), and scanning transmission electron microscopy (STEM) with Cathodo-luminescence(CL) capability. This phalanx of complementary, advanced spectroscopic techniques enables us to investigatethe electron-phonon coupling with unmatched spatial resolution, providing not only insight into devicelimitations, but also a fundamental understanding of carrier relaxation and dephasing processes.
With TERS we analyze how the tip-induced electric field and the plasmonic coupling between the metal tip
and the (doped) sample influence the Raman signature depending on the carrier concentration. Such measurementsare not only of importance for studying localized phonons in, e.g. nanowires (NWs) and singlequantum dots (QDs), but also for understanding the nature of the enhancement process itself. Hence, TERSis most valuable for the interpretation of μPL and CL results, directly reflecting the coupling between theelectronic and phononic states. Based on our combination of ultraviolet (UV) enhanced μPL and CL, bothproviding the capability for ps time-resolved and correlation spectroscopy, we identify, e.g. single-photonemitters in nitride QDs paving the way towards efficient single- and two-photon emitters. The exceptionallystrong coupling between e.g. excitons and phonons in nitride nanostructures even fosters the generation ofsingle, confined phonons, exploring new device concepts at the interface of photonics and phononics based on single phonon emission and storage. Our recent discovery of hybrid-quasiparticles with unconventionaltotal spin numbers is fundamentally related to phonon-induced spin flip process of carriers benefitting fromsizeable coupling constants in especially nitride-based quantum dots.

Event learning consists of different learning phenomena with very different emotional and behavior consequences: fear learning, relief learning and safety learning. In the proposed project, we want to characterize these three learning phenomena in laboratory rodents, investigate their neural basis and dissociate them from each other. Since fear learning is already well investigated, we want to focus on relief and safety learning. Beside the neural, pharmacological, molecular and genetic basis of event learning, we are also interested in the question how trait anxiety affects event learning and related cognitive flexibility.

Integrating ICT in education successfully requires teachers who are competent in using ICT in instruction. With the study at hand, a pre-service teacher course is developed including theoretical, empirical and practical approaches in order to analyze how the differentiated facets of pedagogical media competence can be fostered in teacher education.
Integrating ICT in education successfully requires teachers who are competent in using ICT in instruction in order to support learning processes, foster students¿ ICT and media literacy and promote school development processes with regard to ICT. So far, teacher education in Germany scarcely allows for a systematical development of pedagogical media competence. Evaluations of existing concepts are even rarer.
With the study at hand, a pre-service teacher course is developed including theoretical, empirical and practical approaches in order to analyze how the differentiated facets of pedagogical media competence can be fostered in teacher education. Additionally to the pedagogical media competence framework, the internationally renowned concept of TPACK as well as the European framework DigCompEdu will be covered in the course.
Using a longitudinal design, students¿ self-assessed pedagogical media competence will be measured three times during the course of the semester: at the beginning, after both theoretical and empirical input sessions and last at the end of the course by means of an adapted and extended questionnaire. Furthermore, the pre-service teachers will be asked to maintain a portfolio in which drafts for ICT-based lessons are to be gathered. These drafts will be revised based on peer-feedback by the pre-service teachers and finally evaluated by means of a set of criteria by the course teacher. Complementary interviews conducted with small groups of pre-service teachers at the end of the course will reveal important insights concerning course design, knowledge acquisition and students¿ self-assessments.
The portfolios and interviews analyzed by means of content analysis will supplement the quantitative data acquired in the surveys. Therefore, the study features a triangulative research design.
The study aims at revealing important insights and evidence with regard to the development of pedagogical media competence and shall serve as a basis for the linked integration of this domain in subject didactics and the second phase of teacher education.

Loudness is the perceived intensity of a sound and is an important aspect of hearing. It plays a crucial role when assessing environmental noise. Several standards describe certain aspects of loudness perception. These build on loudness models which are based on hearing experiments with comparatively simple sounds. However, for some environmental sounds, large difference between perception and prediction are observed, especially for sound with strong temporal fluctuations. A reason for this discrepancy may be that not all aspects of loudness perception are included in these approaches. Hearing experiments showed that listeners assign different weights to different portions of the sound. For example, the initial portion of a sound is more important for loudness than later points in time. At present it is unclear if the position of the sound source in space (e.g., in front of the listener or from above) has an impact on loudness. The first aim of the project is to gain a better understanding of how weights are assigned by humans when evaluating the loudness of a sound. The second aim is to develop a new loudness model on the basis of existing data as well as on the data that will be collected in the project. In contrast to present loudness models, this new model will include a specific weighting of different components of the sound when calculating its loudness.

Quality metrics are a promising concept for the automatic analysis of visualizations from high-dimensional data.  ln order to completely visualize a high-dimensional  data set, a large number of visualizations are required.  Just a subset of them shows relevant structures  of the data and thus just a subset of  themis required to be seen by the user.  The idea of quality metrics is to automatically detect this subset of "good" visualizations.  For this, they mimic the visual perception system.  A couple of quality metrics are known aiming mostly at the analysis of bi-variate discrete visualizations of high-dimensional data.  This project extends the traditional approach of quality metrics in three ways. The concept of quality metrics will be extended to nonlinear embeddings  in multivariate projections, it will be extended to non-discrete visualizations (aka continuous visualizations), and it will be extended in order to measure the reliability of quality metrics.  As the conceptional extensions are mutually related, we propose their treatment within one project.

The classical theory of elasticity is an integral part of the daily routine of engineers. It was placed on a firm theoretical foundation between the beginning of the 19th century and the mid-20th century. Its development can be considered complete. Unfortunately, its scope is limited: It is size insensitive, it contains singularities in the stresses and displacements when discontinuities appear in the boundary data, and can not include boundary and surface energies. Thus, it is limited to typical engineering applications. For the description of micro-components or phenomena in the micron- and nanometer range it is only partially suitable.

A natural extension of classical elasticity is the strain gradient elasticity, in which higher derivatives of the displacement field appear. It has been shown in numerous papers that the limitations of classical elasticity theory can be overcome with gradient expansion without blurring the usual separation between structure- and material properties, as is the case with alternative nonlocal theories. Unfortunately, it has not yet been possible to develop a complete solid foundation for gradient elasticity as it exists for classical elasticity theory.

This is not a purely academic matter. The increasing miniaturization of components and the targeted development of micro-structured materials require us to go beyond the classical theory of elasticity. Furthermore, by removing the singularities of classical elasticity, we are able to apply a number of criteria (e.g. fracture and flow criteria), which are usually formulated in the Cauchy stresses, also in the vicinity of boundary discontinuities. This significantly increases the applicability of the elasticity theory.

In this project, the well-established theoretical foundations of classical elasticity are to be expanded to strain gradient elasticity. For this purpose, a generalizing axiomatic theory has been worked out, about 2/3 of which have already been transferred to the gradient theory. We try to complete this transfer, which is the core of the work of the German project partner. The Russian project partner is concerned with specific applications. For example, uniqueness theorems for boundary value problems with pure displacement or pure stress boundary conditions are applied in homogenization. With them, for example, the Eshelby fundamental solution of an elliptical inclusion in an infinite matrix can be extended. Another application are transversely isotropic fiber-reinforced composites, for which both a scale transition and the specific properties of the stiffness tensor are to be investigated. Finally, the de Saint-Venant principle for gradient elasticity will be investigated in beam experiments.

Dr.-Ing. Sascha Duczek has organized this research project, which is financially supported by the German Research Foundation. This project is aimed at extending the Spectral-Cell-Method (SCM) to unstructured discretizations. The investigation is focused on different types of unstructured meshes and the development of appropriate higher order nodal or modal ansatz functions. Among the numerous elements which can be used for creating unstructured meshes tetrahedral elements have special properties. Note that any geometry can be simply meshed with the help of available powerful software tools. Therefore, an important first step of the project is the development of the Tetrahedral-SCM. But, the general approach to higher order elements and unstructured meshes is developed in such a way that new special element types, such as prismatic, pyramidal or any polygonal-shaped elements can be included step by step into the new simulation software.

The development of strategies that effectively combine T cell directed immunotherapy with the inhibition of tumor-promoting signal transduction pathways for the treatment of melanoma represents one of the most important current clinical challenges. The principle goal of this proposal is to experimentally evaluate such strategies using state-of-the-art preclinical genetically engineered mouse models. In our work we will investigate the general hypothesis that IFN-driven cytotoxic CD8+ T cell immunity is limited locally in the melanoma microenvironment by both physiologic protective responses and by the immunosuppressive activity of melanoma cells. These counter-regulatory mechanisms include the recruitment of myeloid immune cells into injured tumor tissue, the stimulation of PD1/PDL1 immune-inhibitory receptor interactions, and the generation of an immunosuppressive milieu by the activity of oncogenic signalling pathways in tumor cells. The experimental work is directed at interfering with these mechanisms and is divided in three parts with the following aims: (i) to characterize the role of type I IFNs for the regulation of anti-tumoral CD8+ T cell responses; (ii) to establish in vivo bioluminescence imaging techniques to non-invasively evaluate the efficacy of therapeutic strategies that modulate both the infiltration of melanoma tissue with adoptively transferred cytotoxic CD8+ T cells and the subsequent recruitment of myeloid immune cells; and (iii) to expand our model system and explore treatment protocols that combine adoptive CD8+ T-cell therapies with BRAF(V600E) signal transduction inhibitors. The proposed experiments will yield fundamental insights into the possibilities to combine T cell immunotherapies with the inhibitors of tumor-promoting signal transduction pathways. This will provide valuable information for ongoing and future clinical translational studies in patients with metastatic melanoma.

GABAergic interneurons are critical for the acquisition, consolidation, retrieval and extinction of aversive memories. Here  we want to address the role of the identified GABA interneuron populations in interactions of hippocampus and frontal cortex controlling cognitive flexibility. We propose that ventral hippocampal basket cells by determining the stability of previously acquired memories can restrict the degree of flexibility initiated in prefrontal and orbitofrontal areas. Dorsal hippocampal HIPP cells, in contrast, via the anterior cingulate may help adopting novel task solutions by disambiguating similar conditions and configurations. We will employ the established tools of immunohistochemical mapping, mRNA expression profiling with laser microdissection and quantitative PCR, and pharmacogenetic manipulation in cell-specific driver mice to examine the activation and function of GABA neurons with respect to cue/context balance and pattern separation during aversive learning, recruitment of spatial and non spatial learning strategies, reversal learning in spatial and go/nogo tasks. We will use both ex vivo slice preparations and in vivo recordings of hippocampus and frontal cortex to examine the neurophysiological correlates of such interneuron function. Thereby we expect to obtain a comprehensive picture of interneuron-mediated circuit activity and the involved molecular factors relevant for behavioral and cognitive flexibility.

The aim of the present project is to develop an analytical approach for the determination of optimal designs for the problem of prediction in hierarchical random coefficient regression models as well as in generalized linear and nonlinear mixed models. Such models were initially introduced in bio- and agricultural sciences and are nowadays utilized in an increasing number of fields in statistical applications.

The aim of the present project is to develop an analytical approach for the determination of optimal designs for the problem of prediction in hierarchical random coefficient regression models as well as in generalized linear and nonlinear mixed models. Such models were initially introduced in bio- and agricultural sciences and are nowadays utilized in an increasing number of fields in statistical applications.

Aberrant expression, overexpression or signal reprogramming of G-protein coupled receptors (GPCR) and G-proteins have been linked to cancer development and progression. The important role of GPCR-Gaq signaling in melanocyte neoplasia became apparent with the discovery of somatic Gnaq mutations in blue melanocytic nevi in the skin and in uveal melanomas. The principle goal of our proposal is to gain deeper insight into the role of Gnaq/11 signaling in melanoma biology. Our work is based on the general hypothesis that activated Gnaq/11 signaling can promote melanoma cell proliferation and tumor growth but also migration and metastatic disease progression in a defined microenvironmental context that provides strong receptor tyrosine kinase driven survival signaling. From our analyses we expect new general insights into the molecular mechanisms why and how mutant Gaq/11 signaling drives growth and metastasis of certain melanoma subtypes. We also hope to provide a basis for the development of novel therapeutic approaches targeting deregulated Gaq/11 signaling which is particularly important for patients with uveal melanoma.

Aberrant expression, overexpression or signal reprogramming of G-protein coupled receptors (GPCR) and G-proteins have been linked to cancer development and progression. The important role of GPCR-Gaq signaling in melanocyte neoplasia became apparent with the discovery of somatic Gnaq mutations in blue melanocytic nevi in the skin and in uveal melanomas. The principle goal of our proposal is to gain deeper insight into the role of Gnaq/11 signaling in melanoma biology. Our work is based on the general hypothesis that activated Gnaq/11 signaling can promote melanoma cell proliferation and tumor growth but also migration and metastatic disease progression in a defined microenvironmental context that provides strong receptor tyrosine kinase driven survival signaling. From our analyses we expect new general insights into the molecular mechanisms why and how mutant Gaq/11 signaling drives growth and metastasis of certain melanoma subtypes. We also hope to provide a basis for the development of novel therapeutic approaches targeting deregulated Gaq/11 signaling which is particularly important for patients with uveal melanoma.

We propose an approach to represent vector fields (usually resulting from flow simulation or flow measurement approaches) as the (co-)gradient of a scalar field. Since it is known that in general this is
impossible for smooth scalar fields, we introduce the concept of gradient-preserving cuts in scalar fields. We give an exact definition and study its properties. With this, vector fields can be exactly represented as (co-)gradients of scalar fields (2D), or as cross product of two scalar field gradients (3D). We explore whether basedon this we can establish an alternative approach to stream line integration being both faster and more accurate than traditionalintegration techniques. If successful, this influences a number of standard approaches in Flow Visualization. We aim in demonstrating this by introducing new texture based Flow Visualization techniques and new methods for exact Clebsch map computation for 3D divergence-free flows.

Many materials or media in nature and technology possess a microstructure, which determines their macro behaviour. Despite of possible difficulties to describe the morphology of this structure, the knowledge of the relevant mechanisms is often more comprehensive on the micro than on the macro scale. On the other hand, not all information on the micro level is relevant for the understanding of the macro behaviour. Therefore, averaging and homogenization methods are needed to select only the specific information from the micro scale, which influences the macro scale. These methods would also open the possibility to design or to influence microstructures with the objective to optimize their macro behaviour. Study and development of new methods in this interdisciplinary field of actual research will be under the supervision of professors from different engineering branches, applied mathematics, theoretical, and computational physics.

Hypothesis: We hypothesize that proatherogenic micromilieu factors induce normoxic HIF stabilization, leading to molecular fixation of atherogenic maladaptation and loss of EndoC barrier function.

Aims 

1. Systematic analysis of the effect of atherosclerosis-associated micromilieu factors on HIF-1a stabilization under normoxic conditions using a HCS with subsequent imaging-independent verification
2. Functional characterization of HIF stabilizing agents with regard to barrier function and modulation of the EndoC secretome

Autophagy is essential for the maintenance of normal synaptic function. Increased autophagy has been observed under neurodegenerative conditions, but may also protect neurons from the toxicity of intracellular and extracellular aggregates.

In the brain ,autophagy is controlled by the mTOR signaling pathway, which is required for synaptic pruning during development and links autophagy to the state of metabolic activity. However, the routes that control autophagy and their effect on synaptic proteostasis in the aging brain have not been clarified so far.

A new regulator of these processes is the serine / threonine kinase Ndr2. NDR family kinases are involved in the control of proliferation and differentiation, as well as apoptosis signaling, and are known to play an important role in the development and function of the nervous system.

We postulate that Ndr2 is a novel and potent factor for controlling autophagy induction in the brain and can be used to regulate age-related autophagy deficits. In this project, we therefore investigate the effects of altered mTOR-dependent autophagic activity in the aging hippocampus on hippocampal physiology and hippocampus-dependent behavior. In addition, we use targeted molecular and pharmacological intervention to analyze the intracellular signaling pathways, in particular with regard to the role of the serine-threonine kinase Ndr2, and their potential as targets for therapeutic interventions.

Local interneurons critically control activity and plasticity in the hippocampus during memory storage. Strikingly, aging in rodents has been associated with a loss of parvalbumin (PV) and somatostatin (SST) subclasses of hippocampal interneurons, in association with cholinergic dysfunction. Changes in these two cell populations likely contribute to the general alteration of GABAergic inhibition, altered excitation/inhibition balance and reduced capacity to modulate inhibition in the hippocampus of aged rodents. They may also account for disturbances in the propagation of gamma oscillations and altered timing of activity between CA3 and CA1. SST-positive interneurons of the hippocampus appear to be particularly vulnerable to age-related neuropathology and the loss of these interneurons in the hilus discriminates between good and bad memory performers during aging of rats.
The activity of both PV neurons and SST interneurons in the hippocampus are controlled by M1 muscarinic receptors, which in turn have been identified as a major target of pharmacotherapy in dementia and are downregulated in a mouse model of early senescence. In our work, we could recently demonstrate the role of a subgroup of hippocampal SST interneurons in the encoding of context memory salience and identified involved critical molecular components of these cells including the transcription factor CREB, neuropeptide Y and the M1 receptor.

We postulate that PV and SST interneurons mediate the consequences of cholinergic decline on synaptic aging in the hippocampus, and, thus, may serve as target sites for therapy and cognitive enhancement. We therefore in this project define the following aims:

1. We investigate effects of long-term changes in the activity of interneurons and the networks they control on the composition and function of the excitatory synapses of the hippocampus.2. We specifically induce changes in the molecular components that control the activity of interneurons and hippocampal network function, with the aim of counteracting the loss of cognitive performance during ageing.

Mo-Hf-B and Mo-Zr-B alloys as a new class of refractory alloys are potential candidates in stationary and mobile turbine applications. Due to the high melting points of the constituents high-temperature strength and creep strength are expected up to 1,400 °C. Those high service temperatures, in turn, may result in higher turbine efficiencies and may reduce primary energy consumption.

As a manufacturing route, directional solidification via zone melting as a new processing approach for Mo-Hf-B and Mo-Zr-B results in low oxygen (< 50 ppm) impurities, which is essential to avoid embrittlement of these alloys; moreover the materials possess a homogeneous fibre-reinforced microstructure.

An increasing number of individuals are being exposed to infrasound. It is well known that certain individuals may be particularly sensitive and that their quality of life is considerably degraded by a range of symptoms (insomnia, concentration disorders, restlessness, migraine). It is, however, still not clear, how infrasound is processed by human beings. The project aims at investigating the perception mechanisms for infrasound and low-frequency sound. This will provide physicians and psychologists with essential information for an improved examination of the effects such sound has on humans.One hypothesis, how infrasound can be heard, is that the auditory system generates audible distortion products in the audio-frequency range. In order to investigate this hypothesis, it is crucial to rule out that these distortions are produced technically, i.e. by the infrasound stimulus presentation devices. Therefore, the project starts with developing both, distortion-free infrasound sources and sensitive ear canal sound measuring devices. The latter will be used in vivo to quantify the harmonic distortion produced by the human auditory system. Then we will explore the extent to which these distortions are the cause of the perception of infrasound that is, or is not, accompanied by external audio sound. An alternative infrasound perception hypothesis is that infrasound becomes audible because it modulates audio sounds. These two hypotheses will be critically validated by means of listening tests. The results of the latter as well as the technical ear canal sound measurements will be used as the basis for developing models of the infrasound perception processes within this project.The results of this project are believed to lay, in the long run, the ground for future safety regulations and for an adequate characterization of infrasound emission. The results will be important for both protection of health (protection against hazardous infrasound immission) and for economic development (infrasound emission, e.g. manufacturers and operators of wind turbines).

The goal of the Integrated Research Training Group (RTG) School of Nanophotonics of the Collaborative

Research Center SFB 787 (CRC 787) is to attract young researchers and to promote their scientific development.The excellent research environment within the CRC 787 is combined with an in-depth scientific educationand a structured program to advance their professional skills. The RTG encourages the scientific independenceand visibility of its members, provides advanced training and transferable skills, and offers a stimulatingenvironment for scientific exchange, discussions, and education.
The key elements of the RTG are the Doktorandenseminar (participation is mandatory), specialized lectures,
and an annual 3-days CRC workshop for the scientific education. Moreover, transferable-skills workshops, the
annual Nanophotonics day a compact introduction to topics such as patents, career options, etc. , and
travel to international conferences as well as summer schools, in particular the iNOW, is essential for education
in a broader sense. The travel funds provided by the RTG to the PhD students are particularly important for
encouraging the scientific independence and international visibility of the PhD students.

During normal development, children learn to refrain from prepotent response tendencies and to choose or withhold actions on the basis of likely action-outcome contingencies instead. Important prerequisites for this ability are intact sensory motor regulation, feedback processing and to model consequences of our own actions. In project A03, we will examine these fundamental aspects of human action in children and adolescents with attention deficit hyperactivity disorder (ADHD) using established behavioural paradigms in combination with electroencephalography and functional magnetic resonance imaging

Cascade reactions are of special interest in the context of drug discovery. The incorporation of multiple bond-forming events in one process carried out in one pot increases synthetic efficiency significantly and facilitates the generation of various derivatives of intricate molecular structures. Such transformations produce molecular complexity and are thus particularly suitable for the preparation of natural products and analogs as important lead structures in the development of bioactive compounds. Transition metal-catalyzed cascade reactions starting with relatively simple acyclic subunits containing ene and yne fragments provide an atom-economical approach to the one-pot synthesis of complex molecular scaffolds from readily available starting materials. In terms of accessibility propargyl alcohols are particularly noteworthy. They are directly accessible from aldehydes or ketones by acetylide addition. Especially the 1-alkenyl propargyl alcohol motive is a very versatile C5-subunit, since all five carbon atoms are selectively addressable by various transition metal catalysts and a broad range of differently substituted alkynes and a,ß-unsaturated aldehydes or ketones are readily available. Due to different functional groups (alkene, alkyne, -OR) several modes of activation can be applied, giving rise to diverse cascade transformations. We discovered that bifunctional (cyclopentadienone)ruthenium(0) complexes and their corresponding imino-derivatives catalyze various addition/cyclization cascades of propargyl alcohols with diverse nucleophiles. The basic coordination site provided by the donor substituted cyclopentadienone ligand and the ligand-metal redox-coupling are crucial for these highly selective transformations. In continuation of our previous research we plan the development of further metal catalyzed cascade processes for the efficient synthesis of polycyclic natural-product-like compounds. The processes are based on ruthenium catalyzed allylation/cycloisomerization-reactions and redox-isomerization/Michael-addition cascades and should also be applied within the total synthesis of bioactive natural products. Asymmetric catalyzed reactions using chiral representatives of the complex series are especially addressed with regard to future applications in the field of natural product and drug synthesis. In addition, options for photocatalytical applications of the developed catalysts should be explored.

The detailed study of pregnancy-associated processes is of pivotal importance for the development of strategies to help reproductively challenged couples. Uterine adaptations to pregnancy are crucial for placentation, in particular for the remodeling of the spiral arteries, a process that implies the conversion of existent spiral arteries into thin-walled arteries as an adaptation to the increasing blood volume. Suboptimal remodeling causes an inadequate supply of nutrients and/or exchange of gases and waste between the mother and fetus that can lead to pregnancy complications such as intrauterine growth restriction (IUGR) and pre-eclampsia (PE). Not only do these changes danger pregnancy itself but they also greatly influence adult health later. Although research has significantly advanced in the last years, still much work is necessary to understand the cellular and molecular mechanisms underlying IUGR and/or PE. An accurate understanding of the basic mechanisms governing both, implantation and placentation is urgently needed. This application aims to understand the participation of cold shock proteins that, until now, have not been studied in the context of pregnancy. Our first experiments suggest a correlation between low  YB-1 and IUGR. In placental tissue from patients with IUGR fetuses, YB-1 mRNA was significantly decreased compared to controls. Thus, low YB-1 levels may be related with poor trophoblast physiology. YB-1 +/- female mice presented an increased number of IUGR feto-placental units compared to the controls at days 8, 10 and day 12 of pregnancy as analyzed by high frequency ultrasound. At day 12, placentas from heterozygote mating combinations presented histological abnormalities, such as disorganized area of spongiotrophoblasts and thin labyrinth. No homozygote fetuses were viable after day 12. We found that animals born to YB-1+/- mothers had thicker artery walls with narrower lumens, resulting in enhanced wall-to-lumen ratio. The fact that YB-1+/+ implantations from YB-1+/- mothers also had abnormal SA suggests that the uterine environment may play a role in the development of SA. Reduced lumen in these animals means an insufficient blood supply to the fetus and thus, a reduced availability of nutrients and oxygen that can lead to growth restriction while in uterus. Hence, we hypothesize that YB-1 mediates relevant pregnancy-associated processes, including placentation and spiral artery remodeling. Trophoblast-specific YB-1 may have the capacity to regulate the finely orchestrated balance between invasion, proliferation, differentiation, apoptosis, and angiogenesis that is essential for the well-being of the fetus and its proper development. By combining elegant animal models and analysis of human tissue samples, we expect to unravel the participation of cold schock proteins in reproduction. These approaches will provide valuable insights into the molecular mechanisms behind pregnancy complications.

In oder to describe properly the macroscopic behavior of agglomerates in a fluid, the flow around each particle must be represented accurately. For this purpose, both organized motion induced by long-range forces (responsible, for instance, for sedimentation and separation) as well as the chaotic motion induced by turbulence must be taken into account in Lattice-Boltzmann (LB) simulations. The flow modifications induced by the particles are also essential to describe the whole system with sufficient accuracy. Local turbulent properties in the boundary layer but also global behavior at system level might be modified with addition of very small particle quantities with specific morphological properties. This will be investigated thanks to LB simulations and experiments, in which non-spherical particles will be added, then tracking modifications of the resulting turbulent features.

In the context of the proposed RTG we understand complexity as an intrinsic property that makes
it difficult to determine an appropriate mathematical representation of a real world problem, to assess the fundamental structures and properties of mathematical objects, and to algorithmically solve a given mathematical problem. By complexity reduction we refer to all approaches that help to overcome these difficulties in a systematic way and to achieve the aforementioned goals more efficiently.

For many mathematical tasks, approximation and dimension reduction are the most important tools to obtain
a simpler representation and computational speedups. We see complexity reduction in a more general way and
will also, e.g., investigate liftings to higher-dimensional spaces and consider the costs of data observation.
Our research goals are the development of cross-disciplinary mathematical theory and methods for complexity
reduction and the identification of relevant problem classes and effective exploitation of their structures.

We aim at a comprehensive teaching and research program based on geometric, algebraic, stochastic, and
analytic approaches, complemented by efficient numerical and computational implementations. In order to
ensure the success of our doctoral students, they will participate in a tailored structured study program. It will
contain training units in form of compact courses and weekly seminars, and encourage early integration into the
scientific community and networking. We expect that the RTG will also serve as a catalyst for a dissemination
of these successful practices within the Faculty of Mathematics and improve the gender situation.

Complexity reduction is a fundamental aspect of the scientific backgrounds of the principal investigators.
The combination of expertise from different areas of mathematics gives the RTG a unique profile, with high
chances for scientific breakthroughs. The RTG will be linked to two faculties, a Max Planck Institute, and
several national and international research activities in different scientific communities.

The students of the RTG will be trained to become proficient in a breadth of mathematical methods, and
thus be ready to cope with challenging tasks in particular in cross-disciplinary research teams. We expect an
impact both in terms of research successes, and in the education of the next generation of leading scientists in
academia and industry.

The study of light-matter interaction in semiconductor quantum dots
embedded into optical microcavities is a topical research field in
condensed matter physics with many potential applications, such as
ultra-low threshold micro- and nanolasers, single-photon sources, and
sources of entangled photon pairs. The theoretical description of such
driven-dissipative quantum many-particle systems in terms of the
reduced density operator is, however, only feasible for small or highly
symmetric systems. Approaches based on equations of motion of
relevant expectation values are numerically much more efficient, but
require to truncate the many-particle hierarchy at a suitable level and
therefore only provide a subset of moments instead of the full
statistics. In this project, we propose to apply the maximum entropy
method, which was originally introduced in equilibrium statistical
mechanics, to the many-particle hierarchy problem of non-equilibrium
systems in two different ways. The first method still uses the results of
conventional equations-of-motion approaches and allows to
approximately determine the full statistics und substatistics such as
the photon statistics of a microcavity laser. The second method goes
much further by replacing the equations-of-motion approaches for
stationary non-equilibrium problems by a novel scheme which has
three important advantages: (i) it does not require any factorization
scheme to truncate the many-particle hierarchy, (ii) avoids the
numerical integration of equations of motion, and (iii) gives access to
the full statistics. The purpose of the project is to study in detail both
methods with focus on semiconductor quantum-dot microcavity
systems. Once completed, we expect not only to have developed an
highly efficient scheme to solve driven-dissipative quantum many-
particle problems, but also to have gained a deeper understanding of
the many-particle hierarchy and its truncation.

Project B09 deals mainly with cortex-dependent auditory discrimination learning in rodents that is also part of the integrative paradigm. Based on our previous findings we will address the following questions: (i) What is the role of phospholipase Cβ signalling in the formation/consolidation of late memories? (ii) What is the role of bassoon-mediated presynaptic plasticity in learning and memory? (iii) What brain region- and cell type-specific changes in synaptic proteomes occur during memory formation? In particular, what are the molecular mechanistic differences between aversively and appetitively reinforced learning and memory processes?

Many materials or media in nature and technology possess a microstructure, which determines their macro behaviour. Despite of possible difficulties to describe the morphology of this structure, the knowledge of the relevant mechanisms is often more comprehensive on the micro than on the macro scale. On the other hand, not all information on the micro level is relevant for the understanding of the macro behaviour. Therefore, averaging and homogenization methods are needed to select only the specific information from the micro scale, which influences the macro scale. These methods would also open the possibility to design or to influence microstructures with the objective to optimize their macro behaviour. Study and development of new methods in this interdisciplinary field of actual research will be under the supervision of professors from different engineering branches, applied mathematics, theoretical, and computational physics.

As a modern and versatile material, short fiber reinforced concrete (FRC) is nowadays used in many applications, such as tunnel linings or marine structures. To increase the mechanical properties such as the ductility and to reduce crack propagation, the brittle concrete is mixed with short fibers, which results in a complex microstructure, including the concrete matrix, coarse aggregates, and fibers. Under constant long-term loads, creep occurs both in pure concrete as well as in FRC, thus the deformation increases with time.Although creep in FRC is a highly nonlinear process, up to now, only linear approaches for viscoelasticity have been proposed for this material. Furthermore, these models are restricted to uniaxial stress and deformation states. Additionally, the presented models for creep in FRC idealize microstructural features of this material, such as the shape and distribution of fibers and aggregates. To conclude, to date there is no viable approach which takes the complex microstructure into account. So far, numerical models are based on simplifying assumptions resulting in a limited ability to describe physical processes. Therefore, this project aims at developing a new numerical framework for creep of FRC under consideration of the real microstructural components. The procedure is based on computed tomography (CT) scans of FRC specimens, which have been cut from large-scale floor slabs. For the numerical simulation, the scaled boundary finite element method is used in conjunction with the octree algorithm, which allows for an automatized and efficient mesh generation based on the CT data. Thus, the proposed numerical model reflects precisely the real microstructure of FRC.In addition to the numerical framework, a new constitutive model for nonlinear creep of FRC is developed. Thereby, separate constitutive equations are formulated for the concrete matrix, the aggregates, and the fibers. While the mechanical behavior of the aggregates and the fibers can be modelled within the framework of elasticity, a new nonlinear model is developed to account for the inelastic deformations of concrete subjected to multiaxial stress and deformation states. The material parameters are determined based on creep tests on pure concrete, and the constitutive model is implemented into the numerical framework. In order to validate the proposed numerical tool, creep tests are conducted on FRC specimens, such that the resulting experimental data can be compared to the numerical simulation results.Consequently, this project presents a new simulation methodology for creep of FRC, while considering the complex microstructure of this material with high precision. Furthermore, a new nonlinear constitutive model is included into this framework, in order to account for creep deformations of FRC under multiaxial stress and deformation states. This provides the basis for a realistic estimation of the effect of long-term loading on FRC components.

In the frame of the proposed project it is planned to account for the bubble dynamics (i.e. shape oscillations and tumbling motion) in the description of bubble motion, mass transfer and chemical reaction for numerical calculations of reacting bubbly flows by the Euler/Lagrange approach. As a result of bubble dynamics they will perform a tumbling motion and their interface as well as the flow in the vicinity of the bubbles will be continuously modified. This will also yield an increase in bubble residence time. As a consequence, mass transfer and reaction rates will be remarkably improved. So far the influence of bubble dynamics was not accounted for in the numerical calculation of bubbly flows by both the Euler/Euler- and Euler/Lagrange-approach. Hence, such models shall be developed in the proposed project, whereby the numerical calculation of reactive bubbly flows will be remarkably improved.
The numerical calculation of the fluid flow will be based on large eddy simulations (LES) using a dynamic sub-grid-scale (SGS) turbulence model. The influence of the bubbles on the fluid will be accounted for in the momentum equations and in SGS turbulence modelling (i.e. turbulence dissipation and bubble induced turbulence, BIT). The calculation of bubble motion will consider all relevant forces (i.e. base-line model of Liao et al. 2015) and bubble transport by SGS turbulence. In addition, the influence of the Basset force will be examined and a new bubble-wall interaction model will be developed. The bubble dynamics will be accounted for in all three levels of model development, bubble motion, mass transfer and chemical reaction. The dynamic bubble motion will be described through a stochastic variation of bubble eccentricity and orientation using a theoretically based bubble oscillation time scale. Regarding mass transfer and chemical reaction, bubble dynamics will be incorporated in the correlations of Sherwood number and enhancement factor. These correlations will be derived theoretically, supported by the direct numerical simulations of the working group Prof. Bothe (TU Darmstadt). In addition, the Lagrangian simulations will allow supporting the development of a bubble dynamics models in the frame of an Euler/Euler approach proposed by the group of Dr. Rzehak (HZD Rossendorf).
The models for bubble dynamics in bubble motion, mass transfer and chemical reactions (among others for the system Fe-NO) will be stepwise developed and implemented in OpenFOAM. In each working task a detailed validation will be performed based on the experimental studies conducted in various groups of the SPP 1740 (e.g. Prof. Schlüter, TU Hamburg-Harburg; Prof. Kraume TU Berlin; Prof. Hampel, TU Dresden).

The experimental investigation, modelling, dynamic simulation and evaluation of multistage particle cross-flow separation in a turbulent fluid flow was selected specifically for the priority program 1679 DynSim . This typical separation process is used to separate a large number of raw materials, waste, intermediate and by-products in a lot of economic branches. Despite its proven good pro-cess performance, several unsolved processing problems are still connected with it, e.g. fluctuating (turbulent) air flow and particle contents in separation chamber, marked stochastic process dynam-ics as well as resulting insufficient process performance (separation efficiency) and product quality (purity).The thorough solution of these problems requires the development of physically founded, multi-scale and predictive models to evaluate and simulate the process dynamics of interlinked stochas-tic cross-flow separations that will be incorporated in efficient flow-sheet simulations of solid pro-cessing in future.During this project, time and spatially resolved analytical and numerical models will be developed for the process kinetics and interlinked dynamic cross-flow separation behaviour of particles taking into account relevant separation characteristics like size, density and shape. Additionally, steady and unsteady, spatially resolved, computationally efficient numerical simulations of the turbulent flow field will be carried out. By coupling the resulting flow field with the Newtonian and Eulerian equations describing motion and rotation of the particles thanks to the Discrete Element Method (DEM), the trajectories of the particles will be obtained in the real apparatus. After first one-way simulations with simple wall models, coupled computations involving more realistic particle-wall and particle-particle collisions will be considered. The quantitative validation of the employed mod-els will be possible thanks to comparison with time and spatially resolved, three-dimensional Parti-cle Tracking Velocimetry (PTV) measurements in the apparatus. If needed, additional Direct Nu-merical Simulations (DNS) will be considered for the two-phase flow at microscale. The processing and energetic performance (separation efficiency, specific energy consumption) and product quality of separation experiments and numerical tests will be model-aided evaluated and optimized. Next, the calculation and evaluation of dynamic changes of process performance and product quality will follow for step-wise and harmonic oscillations of feed flow, contents, and separation characteristics like particle size density and shape (2nd phase). Finally, these models will be incorporated in a multiscale, modular constructed processing system model able to describe any combined comminution, agglomeration and cross-flow separation processes (3rd phase).

Increasing evidence suggests a critical role of mast cells in neuroinflammatory disorders, but the underlying molecular mechanisms remain unclear. The project aims to characterize cerebral mast cells in detail and to study their intercellular communication within the neurovascular unit by intravital 2-photon microscopy. Furthermore, the impact of mast cells on the blood-brain barrier integrity and vascular activation under acute and chronic inflammation will be studied in vivo using intravital imaging, mast cell-deficient mice and mast cell-specific TNF inactivation. In addition, specialized in vitro techniques will be applied for a detailed analysis of the molecular mechanisms of the blood-brain barrier regulation by mast cells.

Anomaly detection is an interdisciplinary domain, borrowing elements from mathematics, computer science, and engineering. The main aim is to develop efficient techniques for detecting anomalous behaviour of systems. In the classical scenario a monitor receives data from a system and compares this data to a reference system with some single normal behaviour. Ideally no strong assumptions are made on the nature of anomalous behaviours, so the problem of anomaly detection is by essence a non parametric problem. Here I propose to study a more complex scenario, which will be referred to as multisystem anomaly detection. In this setting, reference systems can have a variety of normal behaviours, and moreover, there are many systems under the monitor s surveillance, and the monitor must allocate its resources wisely among them. In this situation new theoretical and computational challenges arise. The overall objective of this proposal is to find efficient methods to solve the problem of multi-system anomaly detection. This aim will be reached by addressing the following sub-objectives. First, we will generalise the theoretical framework of anomaly detection to the broader setting of multi-system anomaly detection. Second, multi-system anomaly detection methods will be developed, by taking ideas from the non parametric testing field and applying them to the new framework. Third, we will study optimal monitoring strategies for cases where the multiple systems cannot be monitored simultaneously. Here, it is important that the monitor allocates its resources among the systems in a way that is as efficient as possible. To this end, sequential and adaptive sampling methods that target the anomaly detection problem will be designed. Since anomaly detection is a non parametric problem, elements in the theory of non parametric confidence sets will be used. Finally, the newly developed methods will be applied to practical problems: a methodological example in extreme value theory, an econometric application for speculative bubble detection and two applications in a Brain Computer Interface framework.

Recent work in this subproject has demonstrated that both implicit and explicit rewards are involved in the incidental learning of repeated spatial configurations. Implicitly, reward signals were obtained from the putamen when a search target was found at a learnt location within a repeated spatial search context. Explicit monetary reward led to enhanced search guidance in repeated configurations. Medial frontal and retrosplenial cortex were core areas of the underlying neural architecture. For the next funding period, we propose to further investigate the nature of reward enhancement of spatial contextual cueing with respect to the role of relative reward value and with respect to the role of reward versus punishment (monetary gain versus loss). In addition, the specificity of the reward-related enhancement will be tested by contrasting context learning and target location probability learning as well as by investigating the contribution of visual working memory capacity. A new aspect will consist of developmental studies of reward modulation of contextual cueing over the lifespan. In particular, we will study age-related changes during learning, expression of learning and relearning of incidentally acquired contextual cues in visual search and examine how the implicit processes interact with motivational factors and working memory capacity.

The TWIN project analyzes the interaction between the immune system and CNS with a focus on neurotrophins. In the 2nd funding period, neuroinflammation and early processes of neurodegeneration were studied in the context of neurotrophin signaling via the p75NTR. In the 3rd funding period, the project will investigate immune cell function and neuronal architecture in mice lacking the neurotrophin BDNF specifically in neurons or in microglia/monocytes and in Bassoon-/- mice, which show increased BDNF secretion. Furthermore, the project will analyze how signaling of the neurotrophin receptor Nogo-A via NgR1/p75NTR controls microglia/monocyte behavior and affects neuronal architecture and function.

Nitride based single photon sources (SPS) for room temperature operation will be fabricated and characterized in this project. A novel approach based on position controlled single GaN/AlN quantum dots (QD) grown by MOVPE inside resonant cavity structures is pursued. Currently, GaN QDs are fabricated either by strained-layer epitaxy, by nanowire growth or by selective area growth Nitride based single photon sources (SPS) for room temperature operation will be fabricated and characterized in this project. A novel approach based on position controlled single GaN/AlN quantum dots (QD) grown by MOVPE inside resonant cavity structures is pursued. Currently, GaN QDs are fabricated either by strained-layer epitaxy, by nanowire growth or by selective area growth [1-3]. In established device fabrication technologies planar surfaces, as usually maintained during strained-layer epitaxy of GaN QDs, are preferable to the 3D surface structures resulting from other approaches. However, nucleation sites of GaN QDs in the self-assembling, planar approach occur at non-predictable random positions and are largely affected by the presence of dislocation networks. We want to overcome this limitation using a nitride-based buried stressor technology that introduces a considerable in-plane stress component at predefined positions at the growth surface of QDs ¿ adopting the successful approach of A2 from the arsenide system to the nitrides. We will therefore develop a well controlled selective lateral oxidation process following an approach by 4] to create a nitride-based buried stressor structure on AlN templates. The impact of such stressors on QD nucleation within a dislocation-rich environment will be studied, particularly making use of the nano-scale resolution of our unique (S)TEM-CL characterization facilities. A technology for single-photon emitter devices will be developed including monolithically-integrated optical elements such as mirrors and resonant microcavity structures as well as micro lenses for enhanced light extraction.
Electronic quantum dot states based on GaN/AlN provide optical transitions (intraband transitions) in telecom-munication regions at 1.3 and 1.55 μm wavelength ¿ an alternative approach to realize SPS for fiber-based secure data communication. For the first time, we will explore fundamental properties of such transitions for generating single photons.

Solid state processes are described by population balance systems. These systems consist in general of coupled partial differential equations characterizing the continuous phase and a population balance equation to describe the dynamic evolution of the solid state.
In the framework of this project, new numerical techniques for the accurate and efficient solution of such systems are developed. This is done in cooperation with the WIAS-Berlin and the TU Hamburg Harburg at the example of the shape-selective crystallization. To simulate such crystallization processes not only adequate solution techniques are required by as well reliable shape dependent crystallization kinetics. These kinetics are determined in several experimental plants. Using the obtained results, new process concepts for the continuous shape-selective crystallization shall be developed and optimized.

Basic objective is the creation of an open-access culture and an awareness for open access within OVGU in conjunction with establishing a long-lasting and reliable open-access infrastructure. The necessary organizational and technical requirements for open access are implemented currently. OVGU Magdeburg establishes sustainable open-access-publishing structures including a DFG publication fund that further increases the reputation of this method.
The OVGU establishes a fund in order to support publications of OVGU members in open access journals. The initial grant by the DFG enables the university to create a reliable structure for financing article-processing charges. The fund sponsors APCs for articles published in genuine, high quality open-access journals. Additional organizational, technical, and legal actions ensure a comprehensive service, enabling OVGU scientists to provide open access to their research results.

In this project adaptive procedure are developed for intelligence tests, which aim at measuring the general intelligence. Test items will be generated automatically and online by a rule-based item generator and adaptively presented. The items will be selected according to the parameter estimates in generalized linear logistic test models. The parameter estimations will be based on optimal designs in order to obtain maximal precision in measuring the intelligence by a minimal number of items to be presented. In detail four types of rule-based test procedures will be constructed for measuring the general intelligence and the necessary basic principles of statistics wikll be developed.

In Phase I rule based items were developed for measuring the working speed and empirically calibrated based on D-optimal dsigns in linear logistic test models with fixed and random factors. Furthermore a programming system was developed for the automatic generation of these items, their adaptive presentation and the estimation of person parameters.
 
In Phase II of this project the work of Phase I has been continued. In analogy to the items on working capacity developed in Phase I rule based items on working speed were constructed, which are suitable for an adaptive testing of this intelligence component. As speed tests were considered, it was necessary to use some extended versions of the Rasch Poisson Count Model as the statistical basis instead of the Logistic Rasch Model of Phase I. For these models again optimal designs were developed for both item calibration and adaptive testing.

In Phase III of this project time trends will be considered for the modelling of intelligence components in longitudinal studies. Also for this situation optimal designs will be constructed which can be used adaptively both within one session as well as over time. Additionally, optimal designs will be provided for the generation of item pools under constraints on the number of rules used.

Modern information technology allows for collecting hugh amounts of data both in terms of units (size) as well as in terms of variables (multivariate observations) which are frequently called "Big Data¿. However, the pure availability of Big Data does not necessary lead to further insight into causal structures within the data. Instead the sheer amount of data may cause severe problems for a statistical analysis. Moreover, in many situations parts (certain variables) of the data are cheap to obtain while other variables of interest may be expensive. Therefore prediction of the expensive variables would be desirable. This can be achieved by standard statistical methods when for a suitable subsample also the expensive variables are available. To reduce costs and/or improve the accuracy of the prediction there is a need for optimal sampling schemes. Concepts of optimal design theory originally related to technical experiments may be deployed in a non-standard way to generate efficient sampling strategies. Basic concepts like relaxation to continuous distributions of the data and symmetry properties may lead to substantial reduction in complexity and, hence, to feasible solutions. To make this general ideas more precise and to put them on a sound foundation to make them applicable to real data constitutes the aim of the present project.

This project is concerned with the problem of learning sequentially, adaptively and in partial information on an uncertain environment. In this setting, the learner collects sequentially and actively the data, which is not available before-hand in a batch form. The process is as follows: at each time t, the learner chooses an action and receives a data point, that depends on the performed action. The learner collects data in order to learn the system, but also to achieve a goal (characterized by an objective function) that depends on the application. In this project, we will aim at solving this problem under general objective functions, and dependency in the data collecting process exploring variations of the so-called bandit setting which corresponds to this problem with a specific objective function.

As a motivating example, consider the problem of sequential and active attention detection through an eye tracker. A human user is looking at a screen, and the objective of an automatized monitor (learner) is to identify through an eye tracker zones of this screen where the user is not paying sufficient attention. In order to do so, the monitor is allowed at each time t to flash a small zone a t in the screen, e.g. light a pixel (action), and the eye tracker detects through the eye movement if the user has observed this flash. Ideally the monitor should focus on these difficult zones and flash more often there (i.e. choose more often specific actions corresponding to less identified zones). Therefore, sequential and adaptive learning methods are expected to improve the performances of the monitor.

The poject focueson the development ofa model-based methodology for systematic component selection and process design for Deep Eutectic Solvents (DES) to be used as mass separation agents in liquid-liquid extraction of target molecules from natural product mixtures. The extraction to tocopherol (Vitamin E) from deodorizer distillate (tocopherol/ methylinoleate), a valuable stream from the vegetable oil production, is taken as example of practical relevance.

Recent insights highlight that CD4+ T cells can contribute to effective tumor immune defense but also participate in tissue homeostasis, regeneration and tumor promotion. The goal of this proposal is to better understand the molecular and cellular mechanisms how the phenotypes and effector functions of CD4+ T cells are regulated in tumor tissues in vivo. We will use adoptive T cell immunotherapy protocols in our experimental mouse melanoma models established in the laboratory. A focus of our work is the immunoregulatory role of neutrophils both locally in the tumor microenvironment as well as systemically.

Non-alcoholic fatty liver disease (NAFLD) is currently the most prevalent liver disease in Western societies with a prevalence of up to 35%. Non-alcoholic steatohepatitis (NASH), the chronic-progressive manifestation of NAFLD is associated with liver cirrhosis and hepatocellular cancer (HCC). Obesity is associated with a pro-inflammatory state, inducing peripheral lipolysis. Cytokine expression and insulin resistance are widely accepted as underlying mechanisms, promoting hepatic steatosis and inflammation. Though, the underlying mechanisms of progression from simple steatosis to NASH are still not known. The applicant could already show a correlation between hepatic cell death and progression from NAFL to NASH in several studies on cell death markers. Altered cell death was followed by massive liver tissue inflammation which may be due to altered NLRP3 inflammasome activation and ER stress. Preliminary data indicate an increased activation of NLRP3 inflammasome and corresponding target genes in liver tissue of NASH patients compared to patients with NAFL. To elucidate the role of NLRP3 inflammasome and enhanced ER stress in NAFLD progression we will analyze different primary murine and human cells (Kupffer cells and hepatic stellate cells) in-vitro, a murine in-vivo NASH model as well as liver samples from NAFLD-patients. Stool samples will be collected from the in-vivo model and patients for analysis of the gut microbiome (richness and composition of bacterial species). The aim is to investigate if NLRP3 inflammasome activation and enhanced ER stress induce inflammation, pro-fibrotic activation as well as different cell death types (apoptosis, pyroptosis, necroptosis) involved in the progression from NAFLD. In addition the effect of an altered microbiome on inflammasome activity and ER stress will be elucidated.

The goal of project A07 is to delineate the functional network level regulation of dopamine release in response to novelty and action for reward and to investigate the relationship between dopamine release and memory consolidation in young and old adults. To achieve these goals, we will continue our successfully established multimodal approach of combining imaging at 3T, 7T and PET. We will achieve a direct integration of fMRI and dopamine release by using a new, truly simultaneous MR-PET facility in Magdeburg. We will also determine whether a norardrenergic brain region, the locus coeruleus, may be a bottleneck for dopamine-release in the hippocampus.

Project A12 addresses the role of the habenula (Hb) in motivated behaviour of humans. The Hb is an important relay on a major descending pathway from the forebrain to the brain stem with predominantly inhibitory influence on monoaminergic nuclei, thereby controlling release of dopamine and serotonin to the forebrain. The project aims at understanding the contribution of the Hb to active and passive avoidance and to learning from aversive events. This comprises studying habenular activity, its structural and functional embedding in pallido-habenulo-mesencephalo-striatal networks, and its neurochemical interactions. To this end, high-resolution structural, diffusion-weighted and functional MRI, pharmacological challenges, and in-vivo receptor density mapping using positron emission tomography will be performed in healthy volunteers. Understanding habenular functions is important not only for fundamental neurosciences but also for clinical neuropsychiatry, because dysfunction of the Hb has been suggested to contribute to the pathophysiology of psychiatric disorders, such as affective disorders and addiction. Therefore, we will search for volume and connectivity aberrations of the Hb in patients with addiction.

This project investigates the perception and neural representation of primary rewards, i.e. tastes, of their visual correspondences (secondary rewards) and of their (mis)matched combination in the human brain. Aims of this project are: (1) to identify the motivational, hedonic and category-specific representations (sweet, sour etc.) of primary rewards, (2) to identify the influence of secondary reinforcers on these representations and (3) to identify the effects of overlearned and novel visuo-gustatory correspondences on these and their functional interplay by means of univariate fMRI-approaches, plus functional connectivity, classification analysis and functional hyperalignment.

Nitride based UV single photon sources for room temperature operation will be fabricated and characterized in this project. Our approach is based on position controlled single GaN/AlN quantum dots grown by MOVPE inside resonant cavity structures using a nitride-based buried stressor. The optical and electronic properties of the individual single quantum dots are analyzed and directly correlated to their atomic real structure by in-TEM cathodoluminescence. Single-photon emitter devices will be developed including monolithically-integra­ted optical elements (mirrors, resonant microcavity structures, micro lenses) for enhanced light extraction. GaN quantum dot intraband transitions will be explored for IR single photon generation at 1.3 and 1.55 µm.

NF-kB is an important transcription factor for development and function of immune cells and is regulated by IkB proteins. IkBNS is an unusual IkB protein and functionally poorly characterized. During the 2nd funding period, we found that IkBNS-/- mice are resistant towards high-dose Listeria infection hinting towards alterations in innate immunity. Indeed, we found high expression of IkBNS in macrophages, neutrophils and NK cells using reporter mice. In the next funding period, we will decipher molecular and cellular functions of IkBNS in these cells using newly established conditional knockout mice that are currently being characterized. This includes IkBNS-dependent leucocyte migration during Listeria infection and functional characterization of target genes and microRNAs.

For visualizing unsteady flow data, the tracing and representation of particle trajectories or path lines is a standard approach. Treating path lines is still less researched than considering stream lines, leading to
the fact that stream line based techniques are much better developed than path line techniques.
This project provides a generic approach to convert path lines of an unsteady vector field v to stream
lines of another (steady or unsteady) vector field w. With this, existing stream line techniques can be used to to visually analyze the path line behavior in v. Based on this, we will develop an approach to texture based Flow Visualization that allows to study the path line behavior in a single image. Also, we intend to contribute to interactive particle tracing in large 3D unsteady flow data sets. Finally, a user study will be designed to evaluate the perception of path lines 2D unsteady vector fields.

In the recent decade, the study of optical microcavities has become an important subject of research in physics. Most prominent are whispering-gallery cavities, e.g. microdisk cavities, where light is confined on a micrometer scale by total internal reflection at the boundary of the cavity. Deforming the boundary of such cavities has led to a variety of applications and interesting physics.

In this project, we are going to employ a perturbation theory to analyze several important aspects of deformed microdisk cavities. We will introduce and study the inverse problem where the far-field emission pattern is given and the corresponding cavity deformation has to be determined. Moreover, we will use the perturbation theory to derive handy formulas for frequency splitting and Q-spoiling. We plan to study the effect of mode coupling on decay rates and relate the perturbation theory to the theory of resonance-assisted tunneling in nearly-integrable quantum systems. Finally, we will use the perturbation theory to analyze the effects of surface roughness.

New production methods enable the design of heterogeneous 3D-System-on-Chips (3D-SoCs), which consist of stacked silicon dies manufactured with different technologies. In contrast to homogeneous SoCs, this allows to adjust the technological characteristics of each die to the specific requirements of the components placed in each layer. Heterogeneous 3D-SoCs provide unprecedented integration possibilities for embedded and high performance systems. To exploit that potential, powerful, flexible, and scalable communication infrastructures are required. Yet, current interconnect architectures (IAs) tacitly assume a multilayer homogeneous 3D-SoC and do not consider the influence of different technology parameters on the topology, architectural, and micro-architectural level of the IA.

In this project, we aim to develop architectural templates and design methods for 3D-interconnect architectures for heterogeneous 3D-SoCs. We target two main innovations: First, we will exploit the specific technology characteristics of individual chip layers in heterogeneous 3D-SoCs. Therefore, we will re-evaluate and extend existing approaches for heterogeneous and hybrid 2D-interconnect architectures. Second, we aim at discovering
new interaction mechanisms among components, which may be spatially distributed even at the micro-architectural level, to exploit their diverse features when manufactured in different technologies. The combination of these aspects leads to technology asymmetric 3D-interconnect architectures (TA-3D-IAs), as defined in this proposal for the first time.

The main outcome of the project will be a deeper understanding of TA-3D-IAs as part of heterogeneous 3D-SoCs. Further, we will develop systematic design methodologies and a set of architectural templates for the design of TA-3D-IAs. Therefor we will create a full-fledged simulation framework for the analysis of TA-3D-IAs' design space, which will be capable of accounting for technology-specific parameters for all components of the communication infrastructure. In addition, we will provide reference benchmarks and selected TA-3D-IAs, which will allow other research teams to evaluate and compare their ideas.

Aging and cognitive decline are highly correlated in the elderly population even in the absence of neurodegenerative diseases. Despite the high burden for each individual and the society as a whole the molecular, cellular, and behavioral underpinnings of cognitive decline are barely understood. We concentrate on synaptic dysbalances involving (i) altered synaptic proteostasis and (ii) altered functionality of the multipartite synapse accompanied by (iii) dysfunctions of the immune system and (iv) changes in neuromodulation as the core for cognitive decline. SynAGE will address these four transversal themes in a joint effort by a team of molecular/cellular and systems neurobiologists to eventually break ground for innovative intervention strategies.

A very important process during early pregnancy is the remodeling of the maternal spiral arteries (SAs) that transport maternal blood to the placenta to provide essential nutrients and oxygen for the fetus. The overall goal of this project is to understand the mechanisms and regulatory pathways involved in the positive effects of MCs and chymases on SA remodeling, a critical process for pregnancy and fetal well-being. In particular I aim to investigate the influence of MCs and chymases on the cellular processes associated with uterine angiogenesis, in particular SA remodeling processes and which factors regulate and influence the function of chymase-producing cells.
The long-term objective of the research is to reveal negative influences on unborn life. Knowledge of the exact SA remodeling mechanisms and the underlying factors is the basis for therapeutic improvements for pregnancy disorders that are substantial for humans worldwide.

This project shall offer new findings for the encoding of spatial information in medical augmented reality (AR) illustrations. New methods for AR distance encoding via illustrative shadows and glyphs shall be investigated. Furthermore, context-adaptive methods for the delineation as well as methods for the encoding of spatial information via auditive feedback are developed. The results can be used to reduce incorrect spatial interpretations in medical AR, to expand existing AR visualization methods and to support physicians during image-guided interventions to reduce the risk of future medical interventions.

Our previous work has shown that the deficits of contextual cueing in search with central vision loss are not due to a failure to learn repeatedly presented configurations, but due to a failure of memory-guided search that goes along with inefficient saccadic exploration of the search displays. In the current project, we want to address this issue with the aim to improve memory-guided search in individuals with central vision loss by improving saccadic exploration.
 
The main problem of eye movement control following central vision loss is that saccades lead to the foveation of peripheral saccade targets. While this is normally adaptive, bringing peripheral points of interest in full view, it is obviously maladaptive after central vision loss, requiring corrective saccades to bring the point of interest into view at a preferred retinal location (PRL) bordering the area of vision loss. What would be more adaptive in this case is to re-reference the saccade target location to an extrafoveal PRL. It is important to note that PRL-use is not the same as saccadic re-referencing to the PRL. In fact, SR has been found to develop only slowly - over months - in clinical populations suffering from foveal vison loss (von Noorden & Mackensen, 1962; White & Bedell, 1990; Whittaker, Cum­mings, & Swieson, 1991). However, recent experiments with central scotoma simulation (Barraza-Bernal et al., 2017; Kwon et al., 2013; Walsh and Liu, 2014; Liu and Kwon, 2016) have demonstrated ways to induce SR over hours rather than months, as reported in the patient studies. While these reports have shown the feasibility of successful SR training with simulated scotomata, they still leave many open questions, as outlined in the work program. Moreover, it took up to 25 hours of training for the fixations with the PRL to become comparably accurate as with the fovea (Kwon et al., 2013), so even a significant reduction of training hours with improved training techniques would be a considerable progress, making future training programs for patients more feasible. Furthermore, the usefulness of SR-training in AMD-patients (instead of study participants with simulated scotomata) still needs to be established.
Because of the slow spontaneous development of saccadic rereferencing and its importance for efficient visual search (including memory-driven search guidance), the main aim of this proposal is the development of an efficient method to train the fast and durable establishment of saccadic re-referencing (SR) to a PRL in the presence of foveal vision loss and to test effects on memory-guided search in the contextual cueing paradigm as well as its transfer to another important task - reading.

Memories of events long past bear on our present motivations and behaviour. Malfunctioning of such long-term mnemonic function has significant clinical consequences. In project B15N, we deal with the ¿where¿ and ¿what¿ of long-term memory. We aim (i) at localizing a long-term associative engram by visualizing de novo protein synthesis → ¿where¿ and (ii) at characterizing this engram¿s molecular content by identifying the newly synthesized proteins → ¿what¿. Requirement for de novo protein synthesis is a characteristic of long-term memory. The respective proteins should be critical for both memory consolidation and the long-lasting storage. Notwithstanding their importance, a comprehensive, cell-specific inventory of these proteins so far does not exist in any organism. To fill this gap, uniquely in Drosophila, we can combine a well-established long-term memory paradigm with in vivo, cell-specific metabolic protein labeling using click chemistry. Converging evidence point to the mushroom body Kenyon cells as the site of coincidence detection for olfactory associative learning in the fly. Individual Kenyon cell-afferent and -efferent neurons have been identified for reinforcement signaling and memory retrieval, respectively. We will metabolically label proteins that are acutely synthesized in Kenyon cells and their critical post-synaptic partners upon olfactory learning. These proteins will be (i) visualized using fluorescent non-canonical amino acid tagging (FUNCAT) to monitor a ¿systems consolidation¿-like process, including its temporal dynamics as reflected in critical time-windows as well as global protein synthesis and turnover rates. The proteins made de novo upon learning will also be (ii) purified using bioorthogonal non-canonical amino acid tagging (BONCAT) and ¿inventoried¿ by mass spectrometry. As a side-track, we will apply these two approaches also to the glial cells as these critically contribute to neuronal function, including long-term memory. Finally, we will (iii) validate the emerging candidate proteins in terms of their causal role in long-term memory using reverse genetics. Given that molecular mechanisms of learning and memory are well-conserved across phyla, we can reasonably hope for translational value of our results.