Thesis (Ph. D.)--University of Missouri--Columbia, 2004. / "December 2004." Typescript. Vita. Includes bibliographical references (leaves 180-210). Also issued on the Internet.

Thesis (Ph.D.)--University of Florida, 2005. / Typescript. Title from title page of source document. Document formatted into pages; contains 171 pages. Includes Vita. Includes bibliographical references.

Yes / After the Battle Dunbar between English and Scottish forces in 1650, captured Scottish soldiers were imprisoned in Durham and many hundreds died there within a few weeks. The partial skeletal remains of 28 of these men were discovered in 2013. Building on previous osteological work, here we report wide-ranging scientific studies of the remains to address the following questions: Did they have comparable diet, health and disease throughout their lives? Did they have common histories of movement (or lack of movement) during their childhoods? Can we create a collective biography of these men? Strontium and oxygen isotope analysis of tooth enamel investigated childhood movement. Carbon and nitrogen isotope analysis of incrementally sampled dentine addressed childhood diet and nutrition. Metaproteomic analysis of dental calculus investigated oral microbiomes and food residues; this was complemented by microscopic analysis of debris in calculus from ingested materials. Selected individuals were examined for dental microwear. The extent of hydroxylation of proline in collagen was examined as a potential biomarker for scurvy. An osteobiography for each man was created using the full range of data generated about him, and these were synthesised using an approach based on the historical method for a collective biography or prosopography. The childhood residences of the men were primarily within the Midland Valley of Scotland, though some spent parts of their childhood outside the British Isles. This is concordant with the known recruitment areas of the Scottish army in 1650. Their diets included oats, brassicas and milk but little seafood, as expected for lowland rather than highland diets of the period. Childhood periods of starvation or illness were almost ubiquitous, but not simultaneous, suggesting regionally variable food shortages in the 1620s and 1630s. It is likely there was widespread low-level scurvy, ameliorating in later years of life, which suggests historically unrecorded shortages of fruit and vegetables in the early 1640s. Almost all men were exposed to burnt plant matter, probably as inhaled soot, and this may relate to the high proportion of them with of sinusitis. Interpersonal violence causing skeletal trauma was rare. Based on commonalities in their osteobiographies, we argue that these men were drawn from the same stratum of society. This study is perhaps the most extensive to date of individuals from 17th century Scotland. Combined with a precise historical context it allows the lives of these men to be investigated and compared to the historical record with unprecedented precision. It illustrates the power of archaeological science methods to confirm, challenge and complement historical evidence. / The excavation and post-excavation programme was primarily funded by Durham University, with the palaeoproteomic analysis funded through the Wellcome Trust www. wellcome.ac.uk (108375/Z/15/Z to CFS).

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The objective of the work carried out in this thesis was to develop analytical and computational tools to model and investigate musculoskeletal human joints. It was recognised that the FEA was used by many researchers in modelling human musculoskeletal motion, loading and stresses. However the continuum mechanics played only a minor role in determining the articular joint motion, and its value was questionable. This is firstly due to the computational cost and secondly due to its impracticality for this application. On the other hand, there isn’t any suitable software for precise articular joint motion analysis to deal with the local joint stresses or non standard joints. The main requirement in orthopaedics field is to develop a modeller software (and its associated theories) to model anatomic joint as it is, without any simplification with respect to joint surface morphology and material properties of surrounding tissues. So that the proposed modeller can be used for evaluating and diagnosing different joint abnormalities but furthermore form the basis for performing implant insertion and analysis of the artificial joints. The work which is presented in this thesis is a new frame work and has been developed for human anatomic joint analysis which describes the joint in terms of its surface geometry and surrounding musculoskeletal tissues. In achieving such a framework several contributions were made to the 6DOF linear and nonlinear joint modelling, the mathematical definition of joint stiffness, tissue path finding and wrapping and the contact with collision analysis. In 6DOF linear joint modelling, the contribution is the development of joint stiffness and damping matrices. This modelling approach is suitable for the linear range of tissue stiffness and damping properties. This is the first of its kind and it gives a firm analytical basis for investigating joints with surrounding tissue and the cartilage. The 6DOF nonlinear joint modelling is a new scheme which is described for modelling the motion of multi bodies joined by non-linear stiffness and contact elements. The proposed method requires no matrix assembly for the stiffness and damping elements or mass elements. The novelty in the nonlinear modelling, relates to the overall algorithmic approach and handling local non-linearity by procedural means. The mathematical definition of joint stiffness is also a new proposal which is based on the mathematical definition of stiffness between two bodies. Based on the joint stiffness matrix properties, number of joint stiffness invariants was obtained analytically such as the centre of stiffness, the principal translational stiffnesses, and the principal rotational stiffnesses. In corresponding to these principal stiffnesses, their principal axes have been also obtained. Altogether, a joint is assessed by six principal axes and six principal stiffnesses and its centre of stiffness. These formulations are new and show that a joint can be described in terms of inherent stiffness properties. It is expected that these will be better in characterising a joint in comparison to laxity based characterisation. The development of tissue path finding and wrapping algorithms are also introduced as new approaches. The musculoskeletal tissue wrapping involves calculating the shortest distance between two points on a meshed surface. A new heuristic algorithm was proposed. The heuristic is based on minimising the accumulative divergence from the straight line between two points on the surface and the direction of travel on the surface (i.e. bone). In contact and collision based development, the novel algorithm has been proposed that detects possible colliding points on the motion trajectory by redefining the distance as a two dimensional measure along the velocity approach vector and perpendicular to this vector. The perpendicular distance determines if there are potentially colliding points, and the distance along the velocity determines how close they are. The closest pair among the potentially colliding points gives the “time to collision”. The algorithm can eliminate the “fly pass” situation where very close points may not collide because of the direction of their relative velocity. All these developed algorithms and modelling theories, have been encompassed in the developed prototype software in order to simulate the anatomic joint articulations through modelling formulations developed. The software platform provides a capability for analysing joints as 6DOF joints based on anatomic joint surfaces. The software is highly interactive and driven by well structured database, designed to be highly flexible for the future developments. Particularly, two case studies are carried out in this thesis in order to generate results relating to all the proposed elements of the study. The results obtained from the case studies show good agreement with previously published results or model based results obtained from Lifemod software, whenever comparison was possible. In some cases the comparison was not possible because there were no equivalent results; the results were supported by other indicators. The modelling based results were also supported by experiments performed in the Brunel Orthopaedic Research and Learning Centre.

Ryanodine receptors (RyRs) are intracellular homotetrameric Ca2+-release channels constituting a family of three different isoforms, named RyRl, RyR2 and RyR3. RyRl and RyR2 are highly expressed in skeletal and cardiac muscles respectively, where they localize in the terminal cisternae of the sarcoplasmic reticulum (SR). Although RyRl and RyR2 have been found to be expressed in several other tissues at much lower level than in striated muscles, their major functional role is related to Ca2+-release from the SR following electrical depolarization of the plasma membrane, a process referred to as excitation-contraction (e-c) coupling and known to regulate striated muscle contraction. The third isoform, RyR3, is characterized by a wide pattern of expression, without any specific association to a tissue or a cell-type. The finding that RyR3 is also expressed in mammalian skeletal muscles parallels the presence of two distinct isoforms, o- and P-RyR, in non-mammalian vertebrate skeletal muscles, and suggests that two functionally distinct RyRs may be involved in the regulation of skeletal muscle contraction. The expression of RyR3 was analyzed in murine skeletal muscle from late foetal stages to adult, throughout neonatal phases of development. RyR3 was expressed widely during skeletal muscle post-natal development, disappearing in all muscles analyzed except diaphragm and soleus. RyR3 knockout mice were generated, and contractile properties of skeletal muscles were analyzed. Skeletal muscle contraction in RyR3-/- mice was impaired during the neonatal phase of development. In skeletal muscles isolated from RyR3-1- mice, the twitch elicited by electrical stimulation was strongly depressed. A significant reduction of the contractile activity was also elicited after stimulation with caffeine, an activator of Ca2+-release through RyRs. In the adults, no differences were detected between wild-type and mutant mice. These results are the first demonstrations of a physiological role of RyR3 in excitation-contraction coupling mechanisms of skeletal muscle, and support the model of a two-channel system regulating skeletal muscle contraction. In order to further characterize the RyR3-1- mouse, [3H]ryanodine binding experiments were performed on diaphragm and total hindlimb skeletal muscles from RyR3+/+ and RyR3-1- mice. Preliminary results will be presented and discussed.