Development of a long life design procedure for Australian asphalt pavements

This project examined the incorporation of the Fatigue Endurance Limit concept into a pavement design procedure. The result of the project was the development of a validated method based off fundamental laboratory testing, which can be used to determine the maximum thickness of an asphalt pavement, beyond which any increase in design thickness will result in little to no increase in the structural capacity of the pavement

Positron emission tomography in vivo characterisation of the pathology of frontotemporal dementia

Frontotemporal dementia (FTD) is clinically and pathologically diverse, encompassing the behavioural variant FTD; non-fluent variant primary progressive aphasia; and semantic variant primary progressive aphasia. These are usually associated with either tau or TDP-43 pathology, with highly variable clinicopathological correlations. Neuroinflammation also contributes to the pathogenesis of FTD, but its relevance to the disease spectrum is incompletely understood. There is a critical need for better understanding of how drivers of pathophysiology, such as neuroinflammation and protein aggregation, relate to the heterogeneity of clinical disease in vivo. This knowledge gap currently forms a significant barrier to the development of effective treatments in FTD. I review the clinical, pathological and genetic features of FTD and the role of PET for measuring in vivo components of pathophysiology in this setting. I then describe a series of case studies and group analysis of FTD syndromes, using positron emission tomography (PET) radioligands to visualise and quantify different aspects of pathophysiology in vivo. [18F]AV-1451tau was introduced primarily to study tau pathology in Alzheimer’s disease using, which differs from FTD tauopathy in several respects. I examined the sensitivity and specificity of [18F]AV-1451 in FTD, in vivo, through (i) [18F]AV-1451 imaging of the FTLD-tau pathology in a case of FTD due to a MAPT 10+16 mutation in the microtubule associated protein tau, and a second pre-symptomatic case with the same mutation; (ii) [18F]AV-1451 imaging of a cohort of seven cases with Semantic Dementia and one case of FTD from a C9orf72 expansion, both strongly associated with TDP-43 pathology without tau; and (iii) the increase in [18F]AV-1451 binding, and changes in the distribution of binding, in thirty one patients spanning the three major FTD syndromes in comparison to matched controls. The literature on the role of neuroinflammation in FTD is more limited. I used the PET ligand [11C]PK-11195, as an established marker of activated microglia. I report the elevation in [11C]PK-11195 binding, and the change in its distribution, in a case of a pre-symptomatic MAPT 10+16 mutation carrier; and in twenty nine patients spanning the three major FTD syndromes in comparison to matched controls. In addition to reporting the correlations between PET ligand binding and disease severity, I describe the relationship across regions and across syndromes between [18F]AV-1451 and [11C]PK-11195 binding. In view of the marked variations in affinity of [18F]AV-1451 for different tau isoforms and TDP43-pathology, my analyses focus on multivariate distributions rather than absolute binding potential. The results show high correlations between [18F]AV-1451 and [11C]PK-11195 binding in each FTD syndrome. However, in the healthy MAPT 10+16 carrier, the distribution of elevated [11C]PK-11195 binding is much more extensive that the elevation of [18F]AV-1451, suggesting that inflammation might precede the aggregation of tau. I discuss the limitations of the PET ligands, and summarise the insights into FTD pathogenesis arising from my series of observational studies. The role of new PET ligands, and the integration of PET in future clinical trials are discussed

The upper Derwent : long-term landscape archaeology in the Peak District.

This thesis is concerned with writing a long-term archaeological landscape history of the Upper Derwent, situated in the Peak District. It is based on fieldwork I have undertaken or directed on behalf of the Peak District National Park Authority between 1994 and 2002 while employed as a Survey Archaeologist. Original field data, gathered by field survey, fieldwalking and excavation, documentary sources and the recorded results of research are discussed as the archaeological evidence for occupation and activity in, and perceptions of, the area. This evidence is integrated into an interpretation of the landscape history of the Upper Derwent, covering a period from the approximate end of the last Ice Age to the modern day. The nature, scale, visibility and chronological resolution of archaeological evidence vary enormously over time. The limitations posed by this variability are addressed, and the opportunities for more in-depth analysis acknowledged. The thesis also explores Andrew Fleming's proposition that we can only interpret the long-term landscape archaeology of an area by exploring the detail of the local evidence in relation to its wider context (Fleming 1990). This takes the 'face-to-face' community as the main focus of study. There are two fundamental issues that have to be addressed in attempting such a study, which are related to reconciling different scales of time and geography. One, is how to write long-term landscape history that covers a time-span extending way beyond a person's comprehension of their past world as understood through personal memory, story-telling and folklore or by other forms of archive. The second is to try to interpret how occupants of a local geographical area interact with regional trends and broader social institutions. I have primarily based my approach on that outlined by Fleming, while also incorporating elements of theoretical developments in landscape archaeology since 1990. Implications of this approach for landscape archaeology are discussed

Integration of Mirror Design with Suspension System using NASA's New Mirror Modeling Software

Advances in mirror fabrication is making very large space based telescopes possible. In the many applications, only monolithic mirrors meet the performance requirements. The existing and near-term planned heavy launch vehicles place a premium on lowest possible mass. Again, available and planned payload shroud size limits near term designs to 4 meter class mirror. Practical 8 meter and beyond designs could encourage planners to include larger shrouds if it can be proven that such mirrors can be manufactured. These two factors lower mass and larger mirrors, presents the classic optimization problem. There is a practical upper limit to how large a mirror can be supported by a purely kinematic mount system and be launched. This paper shows how the design of the suspension system and mirror blank needs to be designed simultaneously. We will also explore the concepts of auxiliary support systems, which act only during launch and disengage on orbit. We will define required characteristics of these systems and show how they can substantially reduce the mirror mass. The AMTD project is developing and maturing the processes for future replacements for HUBBLE, creating the design tools, validating the methods and techniques necessary to manufacture, test and launch extremely large optical missions. This paper will use the AMTD 4 meter "design point" as an illustration of the typical use of the modeler in generating the multiple models of mirror and suspension systems used during the conceptual design phase of most projects. The influence of Hexapod geometry, mirror depth, cell size and construction techniques (Exelsis Deep Core Low Temperature Fusion (c) versus Corning Frit Bonded (c) versus Schott Pocket Milled Zerodur (c) in this particular study) are being evaluated. Due to space and time consideration we will only be able to present snippets of the study in this paper. The advances in manufacturing techniques for lightweight mirrors, such as EXELSIS deep core low temperature fusion, Corning's continued improvements in the Frit bonding process and the ability to cast large complex designs, combined with water-jet and conventional diamond

Sedimentation of the Middle Precambrian Tyler Formation of Northcentral Wisconsin and Northwestern Michigan

A Thesis submitted to the faculty of the Graduate School of the University of Minnesota by Bevan William Alwin in partial fulfillment of the requirements for the degree of Master of Science, June 1976. Plates I-II referenced in the thesis are also attached to this record.The Tyler Formation crops out in a northeasterly-trending belt in Northcentral Wisconsin and Northwestern Michigan along the Gogebic Iron Range. Good exposures are found along several of the major streams draining the area, road cuts and railroad right-of-ways. The Tyler is considered Late Middle Precambrian in age, the Wisconsin equivalent of the Baraga Group of Michigan's Marquette Range Supergroup. The formation was warped and slightly metamorphosed during the Penokean Orogeny (1.7 b. y.). Primary sedimentary structures have been generally preserved. The sedimentologic aspects of seven outcrops in the Hurley, Wisconsin area were studied in detail and a measured stratigraphic section was established. Three distinct lithologies are present, sandstone (graywacke), siltstone and shale in varying degrees of metamorphism. Forty-one percent of the beds measured are argillites or slates and fifty-nine percent are sandstones or siltstones. Volumetrically, the sandstones and siltstones are more abundant than the shale units. A thinning-upward trend in the shale beds suggests a decreasing rate of sedimentation up section which in turn suggests increasing tectonic stability in the source area relative to the depocenter. Alternatively, the thinning-upward trend in the shales may reflect increased periodicity of the events which deposited the coarser-grained elastic beds. A corresponding volumetric increase in sandstones and siltstones up section is explained by the peculiarities of local basin bottom topography. Primary sedimentary structures including alternation of sand-mud units, laterally extensive bedding, graded bedding, rnicrocross-bedding, sole marks, rip-up clasts and Bouma sequences suggest a turbidity current mechanism for sediment transport and deposition in a realtively deep water environment. Twenty-four percent of the beds studied in detail are recognizable turbidites while thirty-five percent do not contain specific telltale sedimentary structures. A grain-flow origin for at least some of these latter beds is suspected. Because of the similarity between the lithologies and facies of the Tyler Formation and the ideal facies sequences of submarine fans, it is suggested that that part of the Tyler Formation which was studied in detail was deposited as part of a submarine fan complex. Indicators of current movement found in the rocks of the Tyler are of several types including both interstratal and intrastratal. Sole marks and cross-bedding are most useful. The currents which deposited the Tyler sediments moved from the east-southeast toward the west-northwest. A new type of sole mark, called a ridge mold or negative groove, is described and a possible method of formation is suggested. Two different methods for estimating current velocity were employed, one based on maximum clast size and one based on spacing of ridge molds. Both methods yielded velocities of a few tens of centimeters per second and primary slope is estimated at 0°10'. Petrology reveals that the major framework constituents of the Tyler graywackes are quartz, plagioclase and rock fragments set in a chlorite- and mica-rich matrix. The "average" graywacke is a lithic graywacke with 28% matrix. Quartz and chert comprise 73% of the framework grains, rock fragments 17% and feldspar 10%. The source terrain was probably mostly granitic with some contribution from older sedimentary, metamorphic and volcanic rocks. The Lower Precambrian rocks to the south and southeast of the Tyler outcrop belt were the probable source. Paleoslope was probably at right angles to current flow. Thus a southern limit to the extent of the Middle Precambrian depositional basin is defined. Similarity of the Tyler and other Middle Precambrian sedimentary rocks in the Lake Superior region suggests a common depocenter in a cratonic basin but at different depositional loci. Reconstruction of current movement and probable source area for the Tyler, Rove and Virginia (Thomson) Formations suggest that the depocenter was landlocked on three sides but may have been open to the northeast

Integration of Mirror Design with Suspension System Using NASA's New Mirror Modeling Software

Advances in mirror fabrication are making very large space based telescopes possible. In many applications, only monolithic mirrors can meet the performance requirements. The existing and near-term planned heavy launch vehicles place a premium on lowest possible mass, and then available payload shroud sizes limit near term designs to 4 meter class mirrors. Practical 8 meter class and beyond designs could encourage planners to include larger shrouds, if it can be proven that such mirrors can be manufactured. These two factors, lower mass and larger mirrors, present the classic optimization problem. There is a practical upper limit to how large of a mirror can be supported by a purely kinematic mount system handling both operational and launch loads. This paper shows how the suspension system and mirror blank need to be designed simultaneously. We will also explore the concepts of auxiliary support systems which act only during launch and disengage on orbit. We will define required characteristics of these systems and show how they can substantially reduce the mirror mass

Minimal breast milk transfer of rituximab, a monoclonal antibody used in neurological conditions.

ObjectiveTo determine the transfer of rituximab, an anti-CD20 monoclonal antibody widely used for neurologic conditions, into mature breast milk.MethodsBreast milk samples were collected from 9 women with MS who received rituximab 500 or 1,000 mg intravenous once or twice while breastfeeding from November 2017 to April 2019. Serial breast milk samples were collected before infusion and at 8 hours, 24 hours, 7 days, and 18-21 days after rituximab infusion in 4 patients. Five additional patients provided 1-2 samples at various times after rituximab infusion.ResultsThe median average rituximab concentration in mature breast milk was low at 0.063 μg/mL (range 0.046-0.097) in the 4 patients with serial breast milk collection, with an estimated median absolute infant dose of 0.0094 mg/kg/d and a relative infant dose (RID) of 0.08% (range 0.06%-0.10%). Most patients had a maximum concentration at 1-7 days after infusion. The maximum concentration occurred in a woman with a single breast milk sample and was 0.29 μg/mL at 11 days postinfusion, which corresponds with an estimated RID of 0.33%. Rituximab concentration in milk was virtually undetectable by 90 days postinfusion.ConclusionsWe determined minimal transfer of rituximab into mature breast milk. The RID for rituximab was less than 0.4% and well below theoretically acceptable levels of less than 10%. Low oral bioavailability would probably also limit the absorption of rituximab by the newborn. In women with serious autoimmune neurologic conditions, monoclonal antibody therapy may afford an acceptable benefit to risk ratio, supporting both maternal treatment and breastfeeding

Evaluation of the Status of the Kemp\u27s Ridley Sea Turtle After the 2010 Deepwater Horizon Oil Spill

Coincident with the 2010 Deepwater Horizon oil spill, unprecedented numbers of Kemp’s ridley sea turtles (Lepidochelys kempii) stranded on northern Gulf of Mexico beaches and the number of nests recorded on the primary nesting beaches plummeted far below expected levels. High levels of strandings have continued since 2010 and the number of nests recovered to approximately 2009 levels in 2011, and improved slightly in 2012. A stock assessment conducted in 2012 indicated that a mortality event occurred in 2010, and that the number of nests should once more exhibit an increasing trend from 2013 and beyond. This has not happened; rather, the number of nests declined sharply in 2013. We conducted a new stock assessment to evaluate additional scenarios, including 1) three stock-recruitment options; 2) the potential that a new source of ongoing mortality is present; and 3) the potential that the number of nests-per-adult-female is dependent on the size of the age-2+ benthic population. The latter model provided the best fit to the data. Further, the preliminary estimate of actual nesting in 2014 is consistent with model projections. The reduction in reproductive output could be due to the combination of a large population and reduced prey levels. Together these may have increased the remigration interval or reduced the number of nests per female. However, research is needed to evaluate this and other plausible hypotheses. Nesting may be highly variable in the future depending on feeding conditions on the foraging grounds

Integration of Mirror Design with Suspension System Using NASA's New Mirror Modeling Software

No abstract availabl

Integration of Mirror Design with Suspension System using NASA's New Mirror Modeling Software

Advances in mirror fabrication are making very large space based telescopes possible. In many applications, only monolithic mirrors can meet the performance requirements. The existing and near-term planned heavy launch vehicles place a premium on lowest possible mass, and then available payload shroud sizes limit near term designs to 4 meter class mirrors. Practical 8 meter class and beyond designs could encourage planners to include larger shrouds, if it can be proven that such mirrors can be manufactured. These two factors, lower mass and larger mirrors, present the classic optimization problem. There is a practical upper limit to how large of a mirror can be supported by a purely kinematic mount system handling both operational and launch loads. This paper shows how the suspension system and mirror blank need to be designed simultaneously. We will also explore the concepts of auxiliary support systems which act only during launch and disengage on orbit. We will define required characteristics of these systems and show how they can substantially reduce the mirror mass