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Essays in empirical economics
Get PDFWhile poverty rates have declined in recent decades, many people are still trapped in poverty with limited opportunities for better living conditions. Moreover, inequality remains high around the globe. Understanding and addressing poverty and inequality is a complex task because it is multidimensional and involves multiple actors. My dissertation contributes to the literature on poverty reduction and inequality by taking an in-depth look at the three channels of Attanasio and Székely's (1999) asset-based framework and relating them to the three actors identified by McKague, Wheeler, and Karnani (2015). It is my hope that my work will shed light on how to address some of the multidimensional aspects of inequality. In Chapter 1, I explore the human capital dimension of poverty and inequality and the potential role governments can play in addressing inequality. Next, in Chapter 2, my thesis ties into the social capital channel of the asset-based framework and analyzes the influence of civil societies. Finally, Chapter 3 speaks to the physical capital channel of the asset-based model and to the potential responsibility of the private sector in addressing poverty and inequality
Miniplatten aus Titan zur Fixation von Gelenkfortsatzfrakturen des Unterkiefers: Evaluation des biomechanischen Verhaltens mittels der Finite-Elemente-Analyse
Get PDFThe current publications aimed first to determine which plating technique provides the most rigid fixation and the best biomechanical behavior and second, to examine how the positioning of the lambda plate affects the rigidity of fixation.
To assess the rigidity of the osteosynthesis, the displacements of the condylar fragments were measured. The von Mises stresses in the osteosynthesis material were calculated to predict possible material failure in the plates and screws. In addition, the maximum principal strain in the bone was used to indicate potential bone areas that might be susceptible to bone resorption. All four plate designs (alpha, kappa, rhomboid, and trapezoidal) were tested under the same conditions: a load of 500 N simulating the maximum masticatory force of a healthy adult and a load of 135 N corresponding to the reduced masticatory force within the six postoperative weeks.
According to our findings, all four plates showed adequate fixation of neck fractures at a load of 135 N with a risk for delayed screw loosening only when the trapezoidal and rhomboid plates were used.
On the other hand, the plates showed significant differences when a load of 500 N was applied. Larger plates requiring more screws for fixation, such as the alpha and kappa plates, performed better than the rhomboid and trapezoidal plates, which have half the volume of the former. The alpha and kappa plates showed higher rigidity and better stress distribution in the bone. The trapezoidal plate resulted in less rigid fixation because the micromovements could lead to pseudoarthrosis.
The above results may differ if the course of the fracture line or the position of the plate changes. These parameters were examined in the current study for the relatively new lambda plate, for which there is insufficient data to make any conclusions about its application. The rigidity of osteosynthesis using the lambda plate was studied for a load of 500N. According to the results of the present study, the lambda plate provided adequate rigidity only for neck fractures. In contrast, the stability of osteosynthesis was unsatisfactory for basal fractures. Furthermore, in condylar neck fractures, a more cranial placement of the plate should be pursued. Finally, if the Lambda plate is used for basal fractures, it should be combined with an additional plate under the sigmoid notch.
The finite element analysis is a computational method, and results apply only to fracture patterns and osteosynthesis materials simulated with current models. The results should be validated by experimental or clinical studies
Characterization of the SAM-key – a conserved regulatory domain of the Fun30 nucleosome remodeler
Get PDFCells need to constantly access their genetic material. However, in eukaryotic cells, DNA is compactly wrapped around nucleosomes and their presence poses a barrier for DNA transactions. To facilitate access, eukaryotes use ATP-driven molecular machines that dynamically shape chromatin structure, called nucleosome remodelers.
Budding yeast Fun30 is the prototype member of the Fun30-SMARCAD1-ETL sub-family of nucleosome remodelers important for DNA repair and gene silencing. While the catalytic mechanism has been elucidated for several remodelers, for this family of single-subunit remodelers we lack mechanistic understanding.
Here we report the discovery of the SAM-key, an evolutionary conserved domain with a sterile alpha motif (SAM)-like fold with one characteristic, long, protruding helix, using structure prediction, multiple sequence alignment and biochemical characterization.
The SAM-key is crucial for Fun30 function, as deletion of the SAM-key from FUN30 in budding yeast leads to DNA repair and gene silencing defects similar to a deletion of FUN30. Biochemical and biophysical characterization of the SAM-key mutant in vitro showed similar folding and stability as wildtype Fun30 as well as wildtype-level binding to DNA and nucleosomes. However, the mutant is deficient in DNA-stimulated ATP hydrolysis as well as nucleosome sliding and eviction. Structure prediction using AlphaFold2 models interaction of the long helix of the SAM-key with protrusion I, a structural element of the conserved 2-lobed ATPase domain that controls catalytic activity in other remodelers. We verified the model and the interaction by crosslinking-mass spectrometry and mutation of the interface with a double point mutant Fun30-ICRR, which phenocopies the SAM-key deletion with defective ATPase activity and nucleosome remodeling. This confirms a regulatory role for the interaction of the SAM-key helix with protrusion I.
Our data thereby demonstrate a central role of the SAM-key domain in mediating the activation of Fun30 catalytic activity, a new insight into the biology of this protein and highlighting the importance of allosteric activation for nucleosome remodelers
Tertiary structures, self-sorting behavior, and formation of an eight helix bundle of helical aromatic δ-amino acid abiotic foldamers in organic solvents
Get PDFThe structure-function relationship of biopolymers inspired the field of foldamers, synthetic oligomers that adopt well-defined three-dimensional structures. In the pursuit of accessing unnatural shapes and functions, different from peptides, research led to the field of abiotic foldamers. In this context, side chain positioning and thereby functional design have been greatly simplified by using oligo-quinolinecarboxamides, known to adopt predictable helical structures. Thus, the formation and shape of a tertiary structure has been successfully predicted by computational modelling and verified by X-ray crystallography. The structure consisted of a helix-turn-helix-motif stabilized by inter-helical hydrogen bonds. In this work the correlation between the conformational preference inherent to each helix and the stability of the tertiary structure was investigated. Therefore, helix-turn-helix sequences were synthesized in which some hydrogen bonds have been removed. Unexpectedly, no strong destabilization of the tertiary fold has been observed. Examination of a new crystal structure revealed that helices adopt their natural curvature when some hydrogen bonds are missing. Otherwise, these hydrogen bonds enforce a spring torsion on the helices, thus causing a conformational frustration as it exists in proteins. This observation also helped increase the understanding of aggregational patterns formed in self-assemblies in which helices were no longer bound to one another by a turn unit. In this case, different kinds of intermolecular hydrogen bonding interfaces in solution have been observed involving two linear arrays of hydrogen bond donors and acceptors at the surface of the helices. In the aim to simplify aggregational behavior, sequences containing only one linear array of hydrogen bond donors and acceptors at their surface have been synthesized. Sequences were synthesized on solid phase and their aggregational behavior examined via solution 1H NMR spectroscopic studies and solid state crystallographic structures. These showed the formation of stable hydrogen bond-mediated dimeric helix bundles that could be either heterochiral (with a P and an M helix) or homochiral (with two P or two M helices). Thus, these foldamers displayed either a social or narcissistic chiral self-sorting behavior. This behavior could be influenced by using different chlorinated solvents, thereby causing quantitative formation of the hetero- or homochiral dimers. Another way to influence aggregation behavior is to forbid PM species by imposing absolute handedness to the helices. Summing up, in this kind of self-assembly a new hydrogen bonding interface imposing some sort of parallelism on the helices has been discovered. However, to access more diverse complex structures, the formation of non-parallel motifs such as tilted dimers, should become more predictable. Therefore, a flexible linker to stabilize a tilted dimer was designed using a crystal structure of such a dimer as starting point. The design was validated. However, the flexible linker also allowed for the discovery of an abiotic, tetrameric, eight-helix bundle. This large (>12 kDa) discrete aggregate is stabilized via inter- and intra-molecular hydrogen bonds, featuring several hydrogen bonding interfaces, including some that had not yet been reported. The discovery of this complex structure provides insights into future designs and enables the prediction of more diverse and sophisticated self-organizations
Modern approaches for component-wise boosting: Automation, efficiency, and distributed computing with application to the medical domain
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