Recreating the Past: Aachen and the Problem of the Architectural "Copy"

This thesis explores the formal, historiographic and critical issues of similitude and the problem of historical memory through Charlemagne's chapel at Aachen and buildings associated with it. In my study, I seek to understand some of the levels on which reference to and appropriation of Aachen reflect the historical, political and cultural moment unique to each of five selected interpretations and how, in these examples, the perception of Aachen provided an image through which contemporary concerns ad meanings could be expressed. The issue, therefore, is not so much what Aachen was like, physically or even ideologically, at the time it was built, but how the chapel was perceived in later times, and, importantly, what the terms of that image were and how that image made the chapel a viable touchstone for later references - often ambiguously termed "copies." These buildings can be seen not simply as subordinate to Aachen, but as works that incorporate an image of Aachen for their own ends; through this incorporation, Aachen can be seen as actually subject to them for its own survival. My study raises the question of what it can mean to remember Aachen and the corollary issue of what it can mean to be like Aachen. My chosen examples underscore that while the chapel remained a potent image, the perception of Aachen as a work of the past as well as the criteria for likeness are changeable and tied to time and circumstance

FANCJ/BACH1 Acetylation at Lysine 1249 Regulates the DNA Damage Response

BRCA1 promotes DNA repair through interactions with multiple proteins, including CtIP and FANCJ (also known as BRIP1/BACH1). While CtIP facilitates DNA end resection when de-acetylated, the function of FANCJ in repair processing is less well defined. Here, we report that FANCJ is also acetylated. Preventing FANCJ acetylation at lysine 1249 does not interfere with the ability of cells to survive DNA interstrand crosslinks (ICLs). However, resistance is achieved with reduced reliance on recombination. Mechanistically, FANCJ acetylation facilitates DNA end processing required for repair and checkpoint signaling. This conclusion was based on the finding that FANCJ and its acetylation were required for robust RPA foci formation, RPA phosphorylation, and Rad51 foci formation in response to camptothecin (CPT). Furthermore, both preventing and mimicking FANCJ acetylation at lysine 1249 disrupts FANCJ function in checkpoint maintenance. Thus, we propose that the dynamic regulation of FANCJ acetylation is critical for robust DNA damage response, recombination-based processing, and ultimately checkpoint maintenance

Reactivity of a Series of Isostructural Cobalt Pincer Complexes with CO_2, CO, and H^+

The preparation and characterization of a series of isostructural cobalt complexes Co(t-Bu)_2(P^EPy^EP)(t-Bu)_2(CH_3CN)_2]-[BF_4]_2 (Py = pyridine, E = CH_2, NH, O, and X = BF_4 (1a-c)) and the corresponding one-electron reduced analogues Co(t-Bu)_2P^EPy^EP(t-Bu)_2(CH_3CN)_2][BF_4]_2 (2a-c) are reported. The reactivity of the reduced cobalt complexes with CO_2, CO, and H^+ to generate intermediates in a CO_2 to CO and H_2O reduction cycle are described. The reduction of 1a-c and subsequent reactivity with CO_2 was investigated by cyclic voltammetry, and for 1a also by infrared spectroelectrochemistry. The corresponding CO complexes of (2a-c) were prepared, and the Co-CO bond strengths were characterized by IR spectroscopy. Quantum mechanical methods (B3LYP-d3 with solvation) were used to characterize the competitive reactivity of the reduced cobalt centers with H^+ versus CO_2. By investigating a series of isostructural complexes, correlations in reactivity with ligand electron withdrawing effects are made

Comparison of dot chromosome sequences from D. melanogaster and D. virilis reveals an enrichment of DNA transposon sequences in heterochromatic domains

BACKGROUND: Chromosome four of Drosophila melanogaster, known as the dot chromosome, is largely heterochromatic, as shown by immunofluorescent staining with antibodies to heterochromatin protein 1 (HP1) and histone H3K9me. In contrast, the absence of HP1 and H3K9me from the dot chromosome in D. virilis suggests that this region is euchromatic. D. virilis diverged from D. melanogaster 40 to 60 million years ago. RESULTS: Here we describe finished sequencing and analysis of 11 fosmids hybridizing to the dot chromosome of D. virilis (372,650 base-pairs) and seven fosmids from major euchromatic chromosome arms (273,110 base-pairs). Most genes from the dot chromosome of D. melanogaster remain on the dot chromosome in D. virilis, but many inversions have occurred. The dot chromosomes of both species are similar to the major chromosome arms in gene density and coding density, but the dot chromosome genes of both species have larger introns. The D. virilis dot chromosome fosmids have a high repeat density (22.8%), similar to homologous regions of D. melanogaster (26.5%). There are, however, major differences in the representation of repetitive elements. Remnants of DNA transposons make up only 6.3% of the D. virilis dot chromosome fosmids, but 18.4% of the homologous regions from D. melanogaster; DINE-1 and 1360 elements are particularly enriched in D. melanogaster. Euchromatic domains on the major chromosomes in both species have very few DNA transposons (less than 0.4 %). CONCLUSION: Combining these results with recent findings about RNAi, we suggest that specific repetitive elements, as well as density, play a role in determining higher-order chromatin packaging

Work-Family Conflict and Work Exit in Later Career Stage.

This study investigated relationships between work–family conflict and routes of later-life work exit

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Restoring Charlemagne’s chapel: historical consciousness, material culture, and transforming images of Aachen in the 1840s

The 1840s offer crystallizing images of Charlemagne’s chapel at Aachen that continue to resonate. In this decade, the Carolingian building, restored in words and images by scholars, made an auspicious debut within the coalescing discipline of art history. Simultaneously, the well-known restoration of the extant medieval chapel, which began in the 1850s, found sure footing as the chapel’s columnar screen, which Napoleon had removed, was reinserted. While these co-existing, interrelated restoration movements – focused on the chapel’s dilapidated state and notions of its importance as an imperial, Christian, and German work – diverged in methods and results after mid-century, they remain central to understanding both the chapel in scholarship and the extraordinary monument in the town centre of Aachen today

Development of CO2-reducing electrocatalysts utilizing non-precious metals supported by pincer ligand scaffolds

The electrocatalytic redn. of carbon dioxide to form usable fuels such as formate, methanol, or higher-order hydrocarbons is an ideal method for alternative energy storage. Compared to heterogenous systems, mol. catalysts are generally more selective, more easily tuned, and allow for detailed mechanistic studies. However, a catalyst remains to be found which is highly stable, utilizes an earth-abundant metal, and operates at a low overpotential with a high rate. Late transition metal complexes supported by pincer ligands have been shown to promote CO_2 insertion into metal-hydride bonds and catalytic CO_2 hydrogenation. Furthermore, efficient and selective electrochem. redn. of CO_2 to formate has been achieved with a PCP-iridium complex in the presence of a proton source. In this study, we evaluate the potential for iron, cobalt, and nickel complexes supported by PNP and PCP pincer ligands to provide a more cost-effective platform for electrochem. CO_2 redn