Erdheim-Chester disease (ECD) represents a clonal non-Langerhans histiocytosis, which manifests under an extensive variety of clinical symptoms. This creates a challenge for the physician, who is required to recognize and diagnose the disease in the early stages. Despite this considerable challenge, in the last decade there has been a dramatic increase in ECD diagnoses, in most part due to an increasing awareness of this rare disorder. Involvement of the axial skeleton is exclusively uncommon with no official recommendations for the treatment of the bone lesions. Here, we present a case report of a young male patient with isolated lesions of the spine, ribs, and pelvis, who was successfully treated with a combination therapy of alfa-interferon and zoledronic acid.

RNA processing events that take place on the transcribed pre-mRNA include capping, splicing, editing, 3′ processing, and polyadenylation. Most of these processes occur co-transcriptionally while the RNA polymerase II (Pol II) enzyme is engaged in transcriptional elongation. How Pol II elongation rates are influenced by splicing is not well understood. We generated a family of inducible gene constructs containing increasing numbers of introns and exons, which were stably integrated in human cells to serve as actively transcribing gene loci. By monitoring the association of the transcription and splicing machineries on these genes in vivo, we showed that only U1 snRNP localized to the intronless gene, consistent with a splicing-independent role for U1 snRNP in transcription. In contrast, all snRNPs accumulated on intron-containing genes, and increasing the number of introns increased the amount of spliceosome components recruited. This indicates that nascent RNA can assemble multiple spliceosomes simultaneously. Kinetic measurements of Pol II elongation in vivo, Pol II ChIP, as well as use of Spliceostatin and Meayamycin splicing inhibitors showed that polymerase elongation rates were uncoupled from ongoing splicing. This study shows that transcription elongation kinetics proceed independently of splicing at the model genes studied here. Surprisingly, retention of polyadenylated mRNA was detected at the transcription site after transcription termination. This suggests that the polymerase is released from chromatin prior to the completion of splicing, and the pre-mRNA is post-transcriptionally processed while still tethered to chromatin near the gene end.

The following essay discusses Herman Melville’s “I and My Chimney” (1856) as a text that engages architecture and writing as interrelated systems of signification. Fueled by a variety of historical developments, domestic architecture emerges as a powerful purveyor of meaning in the antebellum decades. Architecture, in this cultural context, is construed in analogy to writing (and, to some extent, vice versa), as creating houses-as-texts that tell stories about their inhabitants in terms of their individual, familial, and national identities. Thus conceived, domestic architecture is characteristically enlisted in the articulation and stabilization of hegemonic narratives of, e. g., gender and nationhood. Melville’s text invokes this cultural convention to cast the signifying function that architecture and writing perform as being vulnerable and in crisis. This crisis is narrated by an idiosyncratic narrator for whom the semiotic instability documented by his narrative resonates with the social and cultural vulnerability that he experiences—his authority as master of his house and family is challenged in the course of the tale, along with the structural integrity of his chimney with which he wants to symbolically reinforce his authority. I argue that this crisis of signification performs double work in the text. On the one hand, it serves to articulate the anxiety of mid-nineteenth-century cultural elites about what they perceive as a cultural decline. On the other hand, allegedly dysfunctional signification unfolds a critical potential, bringing to light things which ‘functional’ signification had worked to conceal and thereby unlocking hermetic narratives of self, family, and nation.

Die vorliegende Diplomarbeit beschäftigt sich mit der Ist-Analyse und Bewertung der Radverkehrsinfrastruktur auf dem Campus der Technischen Universität Dresden. Die Analyse stellt eine wichtige Aufgabe dar, da auf Grundlage von renommierten Haushaltsbefragungen, dem System repräsentativer Verkehrsbefragung und der Mobilität in Deutschland, von einer tendenziellen Zunahme des Radverkehrs in Deutschland gesprochen werden kann. Auch im internationalen Bereich sind diese Entwicklungen anhand von Statistiken nachweisbar. Infolgedessen ist mit einer steigenden Nachfrage bei entsprechenden Radverkehrsinfrastrukturen zu rechnen, deren Qualität einen maßgeblichen Einfluss auf die Attraktivität des Radverkehrs und die weitere Entwicklung dieses nachhaltigen Verkehrsmittels hat. Zur Förderung der Infrastruktur sind Strategien, Konzepte und Programme notwendig, wobei im Rahmen dieser Arbeit einige Best-Practice-Beispiele zu Radverkehrskonzepten an Universitäten präsentiert werden. Die Umsetzung und Finanzierung von Maßnahmen hängt u. a. von Förderprogramme ab, welche sich zum Großteil auf länderübergreifende Maßnahmen beschränken. Im Rahmen einer Literaturrecherche wird geklärt, inwieweit direkte und investive Förderprogramme für die Radverkehrsinfrastruktur an Universitäten existieren. Das Hauptaugenmerk dieser Arbeit liegt auf der Herleitung eines Bewertungsverfahren und der Analyse der Radverkehrsinfrastruktur anhand von gewählten Kriterien und Parametern, wobei gemäß der systematischen Betrachtung des Radverkehrs die technischen und organisatorischen Infrastrukturen untersucht werden. Die Gewichtung konzentriert sich dabei verstärkt auf die Fahrradabstellanlagen am Campus der Technischen Universität Dresden, welche analysiert und anhand eines Punktesystems klassifiziert, jedoch im Vergleich zu den anderen zu untersuchenden Kriterien jeweils einzeln bewertet werden. Als Resultat der Analyse und Bewertung lässt sich schlussfolgern, dass Nachholbedarf bei der Radverkehrsinfrastruktur am Campus der Universität besteht, welche insgesamt mit der Note \"ausreichend\" zu bewerten ist. Letztendlich fehlen einige Infrastrukturen oder entsprechen nicht den Ansprüchen an eine fahrradfreundliche Gestaltung. Anhand einer SWOT-Analyse werden die Ergebnisse interpretiert und Handlungsempfehlungen bzw. harte und weiche Maßnahmen zur Verbesserung der Radverkehrsbedingungen abgeleitet.

Background: Behavioral disturbances following chemotherapy with cisplatin are rare. Here, we report a patient with temporary loss of moral behavior in the setting of cisplatin-based chemotherapy for treatment of tonsillar cancer. Case presentation: A 66-year-old Caucasian male with no psychiatric or violent history was started on chemotherapy with cisplatin for treatment of tonsillar cancer. During the following weeks, the patient developed profound personality changes involving volatile emotions and impulsive aggression with verbal and physical assaults on others. Admitted to the hospital, the patient lacked any awareness that his behavior was wrong. Chemotherapy was discontinued and the patient was prescribed risperidone. Aside from mild cognitive impairment, comprehensive neuropsychological, neuroradiological and lab testing were unremarkable. Three weeks following cessation of chemotherapy, the patient had recovered to his original mental state and he was completely aware of his wrongdoing and social misconduct. Conclusion: Since neurotoxic effects of chemotherapeutics on the brain are not yet sufficiently elucidated, our case emphasizes that early signs of behavioral abnormalities in patients receiving chemotherapy should trigger comprehensive psychiatric evaluation and ongoing monitoring of the patients’ mental state.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Mémoire numérisé par la Direction des bibliothèques de l'Université de Montréal.

Production of mutant biological molecules for understanding biological principles or as therapeutic agents has gained considerable interest recently. Synthetic genes are today being widely used for production of such molecules due to the substantial decrease in the costs associated with gene synthesis technology. Along one such line, we have engineered tRNA genes in order to dissect the effects of G:U base-pairs on the accuracy of the protein translation machinery. Our results provide greater detail into the thermodynamic interactions between tRNA molecules and an Elongation Factor protein (termed EF-Tu in bacteria and eEF1A in eukaryotes) and how these interactions influence the delivery of aminoacylated tRNAs to the ribosome. We anticipate that our studies not only shed light on the basic mechanisms of molecular machines but may also help us to develop therapeutic or novel proteins that contain unnatural amino acids. Further, the manipulation of the translation machinery holds promise for the development of new methods to understand the origins of life. Along another line, we have used the power of synthetic biology to experimentally validate an evolutionary model. We exploited the functional diversity contained within the EF-Tu/eEF1A gene family to experimentally validate the model of evolution termed ‘heterotachy’. Heterotachy refers to a switch in a site’s mutational rate class. For instance, a site in a protein sequence may be invariant across all bacterial homologs while that same site may be highly variable across eukaryotic homologs. Such patterns imply that the selective constraints acting on this site differs between bacteria and eukaryotes. Despite intense efforts and large interest in understanding these patterns, no studies have experimentally validated these concepts until now. In the present study, we analyzed EF-Tu/eEF1A gene family members between bacteria and eukaryotes to identify heterotachous patterns (also called Type-I functional divergence). We applied statistical tests to identify sites possibly responsible for biomolecular functional divergence between EF-Tu and eEF1A. We then synthesized protein variants in the laboratory to validate our computational predictions. The results demonstrate for the first time that the identification of heterotachous sites can be specifically implicated in functional divergence among homologous proteins. In total, this work supports an evolutionary synthetic biology paradigm that in one direction uses synthetic molecules to better understand the mechanisms and constraints governing biomolecular behavior while in another direction uses principles of molecular sequence evolution to generate novel biomolecules that have utility for industry and/or biomedicine.

Das 3. Dresdner Werkstoffsymposium wurde am 6./7. Dezember im Westin Bellevue Hotel Dresden abgehalten. Das Thema lautete "Werkstoffoberflächen für Mensch und Technik".

Die aktuelle Ausgabe des Newsletter für Freunde, Absolventen und Ehemalige der Technischen Universität Chemnitz.