QCD thermodynamics with continuum extrapolated Wilson fermions II

We continue our investigation of 2+1 flavor QCD thermodynamics using dynamical Wilson fermions in the fixed scale approach. Two additional pion masses, approximately 440 MeV and 285 MeV, are added to our previous work at 545 MeV. The simulations were performed at 3 or 4 lattice spacings at each pion mass. The renormalized chiral condensate, strange quark number susceptibility and Polyakov loop is obtained as a function of the temperature and we observe a decrease in the light chiral pseudo-critical temperature as the pion mass is lowered while the pseudo-critical temperature associated with the strange quark number susceptibility or the Polyakov loop is only mildly sensitive to the pion mass. These findings are in agreement with previous continuum results obtained in the staggered formulation.Comment: 19 pages, 13 figures, published versio

QCD thermodynamics with continuum extrapolated Wilson fermions II

We continue our investigation of 2+1 flavor QCD thermodynamics using dynamical Wilson fermions in the fixed scale approach. Two additional pion masses, approximately 440 MeV and 285 MeV, are added to our previous work at 545 MeV. The simulations were performed at 3 or 4 lattice spacings at each pion mass. The renormalized chiral condensate, strange quark number susceptibility and Polyakov loop is obtained as a function of the temperature and we observe a decrease in the light chiral pseudo-critical temperature as the pion mass is lowered while the pseudo-critical temperature associated with the strange quark number susceptibility or the Polyakov loop is only mildly sensitive to the pion mass. These findings are in agreement with previous continuum results obtained in the staggered formulation

Landslide mapping and monitoring by using radar and optical remote sensing: examples from the EC-FP7 project SAFER

This paper focuses on the Landslide Thematic services of the EU-funded FP7-SPACE project SAFER (Services and Applications For Emergency Response) for inventory mapping, monitoring and rapid mapping by using Earth Observation (EO). We exploited satellite Interferometric Synthetic Aperture Radar (InSAR) and Object-Based Image Analysis (OBIA), and discuss example applications in South Tyrol and Abruzzo (Italy), Lower Austria (Austria), Lubietova (Slovakia) and the Kaohsiung County (Taiwan). These case studies showcase the significance of radar and optical EO data, InSAR and OBIA methods for landslide mapping and monitoring in different geological environments and during all phases of emergency management: mitigation, preparedness, crisis and recovery

Aryl Germanes as Ligands for transition Polymetallic Complexes: Synthesis, Structure, and Properties

A series of new carbonyl dichromium complexes bearing aryl germanes as ligands were prepared using improved approaches. The thermal reaction of Cr(CO)6 (1) with Me3GeGePh3 (3) led to the formation of Me3GeGePh[(η6‐C6H5)Cr(CO)3]2 (3a). The lithiation of [(η6‐C6H6)Cr(CO)3] (2) with nBuLi followed by the addition of Me2GeCl2 (4) or ClGeMe2GeMe2Cl (5) gave Me2Ge[(η6‐C6H5)Cr(CO)3]2 (4a) and [(OC)3Cr(η6‐C6H5)]GeMe2GeMe2[(η6‐C6H5)Cr(CO)3] (5a), respectively. The molecular structures of 3a and 4a, in their crystal forms, were studied by X‐ray diffraction analysis. The crystals of oligogermane 3a have shown to undergo a fully reversible phase transition at 160 K without any sign of decomposition. The complexes synthesized were also studied by multinuclear NMR, IR and UV/Vis spectroscopy, DFT calculations and electrochemistry. The presence of a Cr(CO)3 group in a range of oligogermanes has shown to impact on the physical and chemical properties of the compounds

C9orf72 arginine-rich dipeptide proteins interact with ribosomal proteins in vivo to induce a toxic translational arrest that is rescued by eIF1A.

A GGGGCC hexanucleotide repeat expansion within the C9orf72 gene is the most common genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia. Sense and antisense repeat-containing transcripts undergo repeat-associated non-AUG-initiated translation to produce five dipeptide proteins (DPRs). The polyGR and polyPR DPRs are extremely toxic when expressed in Drosophila neurons. To determine the mechanism that mediates this toxicity, we purified DPRs from the Drosophila brain and used mass spectrometry to identify the in vivo neuronal DPR interactome. PolyGR and polyPR interact with ribosomal proteins, and inhibit translation in both human iPSC-derived motor neurons, and adult Drosophila neurons. We next performed a screen of 81 translation-associated proteins in GGGGCC repeat-expressing Drosophila to determine whether this translational repression can be overcome and if this impacts neurodegeneration. Expression of the translation initiation factor eIF1A uniquely rescued DPR-induced toxicity in vivo, indicating that restoring translation is a potential therapeutic strategy. These data directly implicate translational repression in C9orf72 repeat-induced neurodegeneration and identify eIF1A as a novel modifier of C9orf72 repeat toxicity

The two-dimensional Ising-model on Lattices with Trivial Homotopy Group

Contents 1 Introduction 5 2 Thermodynamics, Spin Models and QFT 7 2.1 Basic Thermodynamics . . . . . . . . . . . . . . . . . . . . . . . 7 2.2 Spin Models . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 2.3 Phenomenology of a 2 nd Order Phase Transition . . . . . . . . . 10 2.4 The Relation to Quantum Field Theory . . . . . . . . . . . . . . 12 3 The Two Dimensional Ising-Model 15 3.1 The One Dimensional Ising-Model . . . . . . . . . . . . . . . . . 15 3.2 The Onsager Solution of the Two Dimensional Ising Model . . . 18 4 Boundary Conditions and Finite Size Effects 23 4.1 Finite Size Effects . . . . . . . . . . . . . . . . . . . . . . . . . . 23 4.2 Shift of the Pseudocritical Coupling due to Boundary Effects . . 25 5 Lattice Geometry 27 5.1 Lattice Geometry . . . . . . . . . . . . . . . . . . . . . . . . . . . 27 5.2 Spherical Geometry . . . . . . . . . . . . . . . . . . . . . . .

Identifying modulators of C9orf72 DPRs and STMN2 levels in ALS/FTD using high throughput screening

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases on the same continuum. In this thesis, I will focus on two key genetic and pathological hallmarks of ALS/FTD which have strong therapeutic potential. A hexanucleotide repeat expansion in the gene C9orf72 is the most common genetic cause of familial and sporadic FTD and ALS. Repeat-associated non-AUG (RAN) translation of the repeat containing sequence gives rise to five dipeptide repeat (DPR) proteins, which cause neural toxicity and are hypothesized to contribute to neurodegeneration. RAN translation is an unconventional translation process that may serve as a therapeutic target for C9 ALS/FTD, however, it is not well understood yet. In this study, I generated the first endogenous DPR reporter cell line by genome editing patient-derived iPSCs to tag RAN translation products. Thereafter, I utilized this reporter system to establish a high-throughput screening platform to identify modulators of C9orf72 RAN translation in proof-of-concept screens. By genetic CRISPR nuclease screening, I identified the helicases ERCC8, RTEL1 and UPF1 as selective genetic enhancers of DPR expression. Further, small molecule screening revealed four compounds either increasing or decreasing endogenous DPR levels. These pilot screens validate the capability of our platform that will now be utilized for larger screening campaigns and further be made publicly available. Cytoplasmic mislocalization and aggregation of TDP-43 is a pathological hallmark present in approximately 97% of ALS patients and 50% of FTD patients. Besides a potential gain of toxicity from cytoplasmic aggregates, nuclear depletion significantly disrupts RNA processing. The RNA transcript of the microtubule binding factor STMN2 is amongst the genes most affected by TDP-43 depletion. Enhancing STMN2 levels in the context of TDP43 pathology rescues multiple cellular phenotypes and is therefore an interesting target for therapeutic approaches. Here, I developed a high-throughput screening platform to detect small molecule enhancers of STMN2 protein levels in inducible TDP-43 knockdown cells. After two pilot screens, I performed a high-throughput screening campaign by primary, secondary, and counter screening to characterize compound effects on STMN2. The most potent and selective compounds will now be deeply characterized, chemically optimized, and tested in a phenotypic assay, established during the work of this PhD project. Overall, the work in this thesis generated new tools for the FTD/ALS research community that will hopefully contribute to therapy development. Further, it has enhanced our understanding of the regulation of DPR expression by identifying novel endogenous and small molecule modulators

Nepalese landslide information system (NELIS): A conceptual framework for a web-based geographical information system for enhanced landslide risk management in Nepal

Comprehensive and sustainable landslide risk management, including the identification of areas susceptible to landslides, requires responsible organisations to collaborate efficiently. Landslide risk management efforts are often made after major triggering events, such as hazard mitigation after the 2015 Gorkha earthquake in Nepal. There is also a lack of knowledge sharing and collaboration among stakeholders to cope with major disaster events, in addition to a lack of efficiency and continuity. There should be a system to allow for landslide information to be easily updated after an event. For a variety of users of landslide information in Nepal, the availability and extraction of landslide data from a common database are a vital requirement. In this study, we investigate the requirements to propose a concept for a web-based Nepalese landslide information system (NELIS) that provides users with a platform to share information about landslide events to strengthen collaboration. The system will be defined as a web GIS (geographic information system) that supports responsible organisations in addressing and managing different user requirements of people working with landslides, thereby improving the current state of landslide hazard and risk management in Nepal. The overall aim of this study is to propose a conceptual framework and design of NELIS. A system like NELIS could benefit stakeholders involved in data collection and landslide risk management in their efforts to report and provide landslide information. Moreover, such a system would allow for detailed and structured landslide documentation and consequently provide valuable information regarding susceptibility and hazard and risk mapping. For the reporting of landslides directly to the system, a web portal is proposed. Based on field surveys, a literature review and stakeholder interviews, a structure of the landslide database and a conceptual framework for the NELIS platform are proposed

Comparison and validation of per-pixel and object-based approaches for landslide susceptibility mapping

Remote sensing and geographic information systems (GIS) are widely used for landslide susceptibility mapping (LSM) to support planning authorities to plan, prepare and mitigate the consequences of future hazards. In this study, we compared the traditional per-pixel models of data-driven frequency ratio (FR) and expert-based multi-criteria assessment, i.e. analytical hierarchical process (AHP), with an object-based model that uses homogenous regions (‘geon’). The geon approach allows for transforming continuous spatial information into discrete objects. We used ten landslide conditioning factors for the four models to produce landslide susceptibility maps: elevation, slope angle, slope aspect, rainfall, lithology, geology, land use, distance to roads, distance to drainage, and distance to faults. Existing national landslide inventory data were divided into training (70%) and validation data (30%). The spatial correlation between landslide locations and the conditioning factors were identified using GIS-based statistical models. Receiver operating characteristics (ROC) and the relative landslide density index (R-index) were used to validate the resulting susceptibility maps. The area under the curve (AUC) was used to obtain the following values from ROC for the per-pixel based FR approach (0.894) and the AHP (0.886) compared with the object-based geon FR approach (0.905) and the geon AHP (0.896). The object-based geon aggregation yielded a higher accuracy than both per-pixel based weightings (FR and AHP). We proved that the object-based geon approach creates meaningful regional units that are beneficial for regional planning and hazard mitigation