On the Total Synthesis of Archaeal and Mycobacterial Natural Products

This thesis describes the total synthesis of archaeal and mycobacterial natural products. The synthesis of the tricyclic biphytanediol of crenarchaeol is reported, involving the stereoselective construction of the 5-6-ring motif. Detailed structural analysis of the synthetic material and comparison with analytical data of natural crenarchaeol enabled structure revision of crenarchaeol. Furthermore, this thesis shows the total synthesis of three mycobacterial diacyl trehaloses (DAT1, DAT2 and DAT3) and pentaacyl trehalose (PAT). The synthetic DATs were evaluated for their activation potential of the innate immune receptor Mincle and DAT3 was identified as potent Mincle ligand. Analysis by HPLC-MS and comparison with membrane extracts of Mtb revealed that the structure of synthetic DAT2 does not correspond to naturally occuring DAT2 and it was hypothesized that they are stereoisomers. The total synthesis of PAT included the stereoselective construction of the non-symmetrically substituted trehalose core by glycosylation. The total synthesis of PAT ultimately revealed a mismatch of synthetic and natural PAT. Consequently, research is continuing to revise the chemical structure of natural PAT

The Pathogenesis of Mesh-induced Inflammatory Response and Pain: Rationale for Development of New Mesh

Chronic postoperative pain (CPP) in mesh hernia repair (MHR) may complicate the postoperative course. The cause of CPP may be multifactorial - surgical technique, patient-intrinsic factors, and mesh. Polypropylene (PP) mesh is the most widely used material for MHR. Despite its advantages, it has been associated with severe complications in urogynecology leading to a partial mesh ban. PP is not inert and causes foreign body reactions (FBR), corrosion, and loss in biocompatibility. Pain is a hallmark of mesh-induced complications. The pathogenesis of pain is related to an immune response with neutrophils, T cells, and macrophages, major players in mesh-associated fibrosis and pain. Pain may be caused by mesh implantation-induced nerve entrapment, compression, and severe inflammation, relevant for both nociceptive and neuropathic pain. Compression neuropathy has been associated with preoperative pain and chronic postoperative pain in mesh and non-mesh repairs. The mesh may induce FBR changes causing clinical complications and pain. Increased mesh vicinity innervation induced by fibrosis may be responsible for chronic postoperative pain. An aggressive immune response in pelvic floor reconstructive surgery degrades PP. T cells and macrophages may protect against or induce degradation and pain. The main point to eliminate pain is to develop a mesh, that provides long-term corrosion resistance, and biocompatibility. This may be achieved by coating PP mesh with a thin layer of Titanium oxide or meshes of pure titanium. Titanium is considered to be bio-inert providing corrosion resistance and biocompatibility. However, depending on the location and surface of the mesh (roughness, hydrophilicity), there may be a macrophage-neutrophil-induced inflammatory response causing fibrosis and cicatrization. Based on the structure, location, and production Titanium may demonstrate beneficial effects concerning corrosion, oxidation, FBR, and biocompatibility. To improve outcomes in MHR the analysis of cellular immune response concerning mesh properties, composite endpoints, pain, and physical function may be necessary

Chemical Synthesis of Cell Wall Constituents of Mycobacterium tuberculosis

The pathogen Mycobacterium tuberculosis (Mtb), causing tuberculosis disease, features an extraordinary thick cell envelope, rich in Mtb-specific lipids, glycolipids, and glycans. These cell wall components are often directly involved in host-pathogen interaction and recognition, intracellular survival, and virulence. For decades, these mycobacterial natural products have been of great interest for immunology and synthetic chemistry alike, due to their complex molecular structure and the biological functions arising from it. The synthesis of many of these constituents has been achieved and aided the elucidation of their function by utilizing the synthetic material to study Mtb immunology. This review summarizes the synthetic efforts of a quarter century of total synthesis and highlights how the synthesis layed the foundation for immunological studies as well as drove the field of organic synthesis and catalysis to efficiently access these complex natural products

?Zur Zeit Maler und Dichter? ? DER DOPPELTE GEORGE GROSZ: INTERMEDIALE BEZÜGE ZWISCHEN GROSZ? LYRISCHEM WERK UND AUSGEWÄHLTEN ZEICHNUNGEN

The following thesis examines the poetic oeuvre of George Grosz in relation to selected drawings from the same period of time. A survey of the research on George Grosz shows that the scholarly focus has so far mainly been on his work as a visual artist, whereas his published poems have not been treated with as much attention. Furthermore, there exists no in-depth analysis of possible intermedial relations between his poetic and visual works, although titles of poems and drawings, editorial characteristics of the publication of poems and drawings respectively, and the themes of both suggest a relation between the medially different artefacts of Grosz?s work. The goal of this thesis is to analyse and interpret intermedial relations between Grosz?s poems and drawings and thus affirm their existence as a constituent element of his work. Following Jan Mukarovský?s suggestion of the dual character of content/theme and structure in every artefact, the thesis is subdivided into two separate analyses of content and structure of poems and drawings and their respective intermedial relations. The methodology used to analyse Grosz? work as an intermedial phenomenon draws from the theoretical background of both semiotics and intermediality. Of eminent importance for the methodology are thus Umberto Eco?s works on semiotics and Roland Barthes? works on semiotics in general and on the semantics of visual language in particular. Fernande Saint-Martin?s Semiotics of Visual Language (1990) serves as reference work for the analyses of the structural characteristics of Grosz? drawings and Roman Jakobson?s and Jirý Veltruský?s works on semiotics shed light on the structural differences between verbal and visual language. Furthermore, Irina O. Rajewsky?s systematic introduction to the field of intermedial research, Intermedialität (2002), provides an apparatus with which to categorize structural relations between poems and paintings. The content analysis of poems and drawings focuses on certain recurrent topoi. These are the topoi of the big city, America and (circus) artists. The analyses show intermedial relations and are valuable for the (re-)interpretation of certain topoi, especially when it comes to the evaluation of the Americatopos. The most prominent and dominant topos in both media proves to be the big city. Overall, the analysis of thematic relations mirrors semiotic theory: poems as verbal artefacts are able to provide more content-information than the visual language of the drawings. The structural analysis focuses on certain modes of visual representation as employed by the drawings, and sets out to show intermedial reverberations of the visual structures in the poems and how the verbal structures succeed in evoking certain structural characteristics of visual language in general of and Grosz?s drawings in particular. Whereas there is a semantic advantage of verbal language in the intermedial relations of the contents of the artefacts, the structural analyses show that it is visual structures that govern the relations between poems and drawings. Again, this can be put down to semiotic characteristics: visual language is less strucurally regulated than its verbal counterpart. The conclusion tries to merge the results of the separate analyses by stating that intermedial relations exist and encompass the dualism of content and structure that makes up the artefacts. The specific character of the intermedial relations mirrors the characteristics of the two semiotic systems employed by drawings and poems, i. e. visual and verbal language. Finally, it is suggested that thematic and structural relations are mainly governed by the topos of the big city, which hence can be seen as the thematic and structural paradigm of the analysed poems and drawings by George Grosz and of their intermedial relations

EMG Analysis of Lassimus Dorsi, Middle Trapezius, and Erector Spinae Muscle Activity During Spinal Rotation: A Pilot Study

Purpose/Hypothesis: Spinal rotation is a very common movement that occurs multiple times each day during normal daily activities or even during certain sport performances. Since this motion is a contributing factor to back injuries, it will be important for physical therapists to consider this concept with rehabilitation programs for current back injuries as well as prevention of future injuries. The LD has attachments to many areas of the body, including the spine, humerus, scapula, and pelvis, which explains why this muscle also contributes to multiple actions at the trunk and upper extremity. Due to the attachment sites and the large size of the LD, this muscle is capable of influencing spinal motions during different activities. However, while there is some research regarding muscles involved with spinal rotation, there is currently limited findings for the LD and its contributing factors to spinal rotation. The purpose of this study was to improve the understanding and determine the muscle activity the LD has during spinal rotation and compare that muscle activity throughout different fixed and non-fixed positions. Methods: Participants progressed through ten spinal rotation positions (standing non-fixed rotation right/left, quadruped rotation right/left, and standing rotation right and left with arms fixed on the wall at 45°, 90° and 120° of shoulder flexion). While performing pelvis rotation in testing positions, muscle activity was recorded using EMG surface electrodes. Muscle Activity was normalized by using Maximal Voluntary Contraction (MVC) to normalize muscle activity. Findings were analyzed for significance at α=.05. Results: Significant differences were found in LD EMG activity in fixed and non-fixed movements with the ipsilateral LD being more active in fixed rotation. The ipsilateral LD EMG activity was found to be significantly greater in fixed rotation than right or left MT and ES, as well as the contralateral LD. During non-fixed spinal rotation, the ipsilateral ES EMG activity was found to be significantly greater than the right or left MT and LD, as well as the contralateral ES. Discussion/Conclusion: The findings propose the LD contributes significantly more than the MT and ES during fixed ipsilateral spinal rotation. This implies that while performing closedchain spinal rotation the LD has better positioning to participate in spinal rotation or spinal stabilization. During non-fixed positions the ipsilateral ES were most active during spinal rotation. This suggests that while performing non-fixed rotation the LD is not in optimal position to rotate or stabilize the spine. Future studies should analyze the impact on gender differences, hand dominance, and larger sample size in muscle activation. Clinical Relevance: This study is for clinicians to better understand how the LD, MT, and ES contribute to rotation of the spine. Once clinicians understand how different muscle groups affect spinal rotation, they will be able to improve the evaluation and intervention process in a variety of pathologies such as LBP. Physical therapists will be able to determine the source of pain more efficiently and prescribe more effective exercises. Understanding the actions of these muscles and how they affect spinal rotation will allow the rehabilitation process to be more time efficient and cost beneficial

The Bethania Germans

German immigrants took up land in 1864 in the area of Queensland on the Logan River approximately twenty miles south of Brisbane now known as 'Bethania.' They were followed by others and the settlement spread. The area was identified as German for about 100 years. For the historian the questions are: how the Germans came to this area; how they maintained a more or less German identity for so long; and then why that German identity disappeared. 'Bethania' is an anglicization of the name taken by the Lutheran congregation, 'Bethanien,' the German form of the biblical 'Bethany.' In the 1868 'Queensland Post Office Directory' the name 'Betanien' was applied to the locality occupied by Germans and served by the Logan Reserve post office, but the name did not then come into general usage. 'Bethania' became an official place name from 1885 when the railway station and associated post office were given the name 'Bethania Junction.' The area occupied by the Germans and situated in a bend of the Logan River was referred to as the 'German Pocket,' a somewhat confusing term as there were various German Pockets in Queensland, including one farther down the Logan. For purposes of this thesis it is convenient to refer to the area at all times as 'Bethania.

Directing Coupled Motion with Light:A Key Step Toward Machine-Like Function

Molecular photoactuators can control shape and chemical or physical properties of the responsive system they are embedded in. These effects are usually mediated by supramolecular interactions and can be amplified to perform work at the micro- and macroscopic scale, for instance, in materials and biomimetic systems. While many studies focus on the observable outcome of these events, photoresponsive structures can also translate their conformational change to molecular components and perform work against random Brownian motion. Stereochemical cascades can amplify light-generated motion to a distant moiety of the same molecule or molecular assembly, via conformationally restricted stereogenic elements. Being able to control the conformation or motion of molecular systems remotely provides prospects for the design of the smallest machines imaginable. This Focus Review emphasizes the emergence of directed, coupled motion of remote functionalities triggered by light-powered switches and motors as a tool to control molecular topology and function