The Central Palace Sanctuary at Knossos

This study concerns the central portion of the West wing at Knossos -Evans' Central Palace Sanctuary Area. The aim is to present a full account of the finds, and by their consideration, along with an appreciation of the architecture and stratigraphy, to assess the character and function of the area, in its several phases. The initial chapter largely sets the scene, outlining the course of events of the early excavations, and detailing the primary sources drawn upon here. In each of the following chapters, a separate group of material is presented - a chronological order is maintained in this. In the case of the final phase, the extant architecture is discussed separately from the finds - purely for ease of presentation. A full Catalogue of the Vat Room, Temple Repositories and Final phase finds is then presented; followed by some appendices. The plans, line drawings and plates are in the second volume. The earliest group (late First Palace - MM II essentially) is the Vat Room Deposit: vases and largely fragmentary objects of faience, shell and metals. Recovered from a pit below the gypsum floor, the nature of the finds can reasonably be associated with some cult/ritual activity, but of uncertain nature and position. The abundant material yielded by the Temple Repositories (MM Illb - ?LM 1a) was stowed away deliberately after some destruction: it includes vases, many faience items, bone and ivory, stone, metal and natural objects. Individually and taken together, their character is incontrovertibly to do with a shrine - the location again being uncertain. Much of the finer details of the architecture is ambiguous, though the overall succession of phases is established. The finds associated with the last are mundane - vases; but there is still some hint of ritual interest there. Thus, a thread of continuity may be observed - though the nature of the overall pattern remains debateable. More excavation will be required to proceed further

An investigation of the feasibility of a spacecraft multifunctional structure using commercial electrochemical cells

Multifunctional structures offer the potential for large savings in the mass and cost of spacecraft missions. By combining the functions of one or more subsystems with the primary structure, mass is reduced and internal volume freed up for additional payload, or removed to reduce structural mass. Lithium batteries, increasingly preferred to other power storage solutions, can be employed to produce such structures by incorporating prismatic batteries into structural sandwich panels. Such “powerstructures” can reduce the mass and volume of the power storage subsystem.After reviewing the current work in the field of multifunctional structures, this thesis describes the objective of the research, to examine the usefulness and feasibility of a multifunctional structure based on commercial lithium cells and sandwich structures. The next section presents a study that quantifies the benefits of this technology, showing maximum savings of up to 2% of total mass, and 0.5-1% for common spacecraft designs.The next section describes experimental investigations into the mechanical suitability of commercial PLI cells for use in the multifunctional structure. Firstly, the effect of launch vibration was considered: 15 and 25 grms tests showed no measurable loss in electrical performance. Then, the structural attributes of the cells were measured using a dynamic shear test. The shear modulus of the cells was found to be rather lower than that of an aluminium honeycomb core material.Consideration is then given to the practical implications of a multifunctional structure. The feasibility of manufacturing is assessed through the construction of a trial panel, showing that the cells lose some capacity and suffer an increase in internal resistance in a high-temperature adhesive cure and that a cold-bonding process may thus be preferable. The resultant panel was then vibrated on an electrodynamic shaker to both assess the resilience of the cells and test the reliability of finite element models. These finite element models are then used for a simple optimisation, showing that a welldesigned powerstructure can have structural performance comparable to a conventional design.The final section weighs the benefits of using a multifunctional structure against the potential disadvantages in terms of cost, design time and flexibility, as well as assessing the validity of assumptions made in the work. The conclusion is that a multifunctional structure of this type, whilst not worthwhile for all mission types, could potentially increase the feasibility of short-term spacecraft missions using small satellites (of the order of 100 kg) with large energy storage requirements

Development of a patient-specific finite element model of the transcatheter aortic valve implantation (TAVI) procedure

Transcatheter Aortic Valve Implantation (TAVI) is a procedure developed for replacing the defective aortic valve of a patient as an alternative to open heart Surgical Aortic Valve Replacement (SAVR). In the TAVI procedure a prosthetic valve, which is assembled on to a stent, is crimped and delivered to the patient's aortic root site through several available percutaneous means. The percutaneous nature of TAVI, which is its core advantage in comparison to other SAVR procedures, can however also be its main disadvantage. This is due to lack of direct access to the calcified leaflets, and hence reliance on the host tissue for the proper positioning and anchorage of the deployed prosthetic valve. Therefore, it is desired to have a preoperative quantitative understanding of patient-specific biomechanical interaction of the stent and the native valve to be able to maximise the chance of success of the procedure. The aim of this study was to develop a patient-specific Finite Element (FE) model of the Transcatheter Aortic Valve Implantation (TAVI) procedure for two patients, using a model of the 23 mm percutaneous prosthetic aortic valve developed by Strait Access Technologies (SAT), for the purpose of its post-operative performance. In this regard, the image processing software ScanIP was used to extract the 3D models of the patient-specific aortic roots and leaflets from the provided Multi-Slice Computer Tomography (MSCT) images of the patients. An anisotropic hyperelastic material model was implemented for the roots and leaflets, using two and one families of collagen fibres for their tissues respectively. The stent is made of a cobalt-chromium alloy and its mechanical response was modelled as an isotropic elastoplastic material, with a linear elastic initial response, followed by plastic behaviour with isotropic hardening. The prosthetic leaflets are made of polymer and were modelled as an isotropic hyperelastic material, using the provided experimental test data. The results for the first patient showed that the stent maintained its structural integrity after deployment, and successfully pushed the native leaflets back to keep the aortic root clear of all impediments. No obstruction of the coronary ostia was observed, and prosthetic leaflets were seen to function normally. The stent radial recoil was calculated to be between 2 to 4.28 % after deployments. Its foreshortening was calculated to be approximately 20%. The stent was observed to move back and forth by approximately 3 mm in the last simulation step in which cardiac cycle pressure were applied to the aortic root and prosthetic leaflets. Also, two openings were observed between the stent and aortic root wall during this simulation step, which indicates the possibility of paravalvular leakage. From the second patient simulation, it was observed that the 23 mm stent was not a good choice for this patient, and will cause severe damage or tissue tearing. The maximum principal stress in the aortic root and valve tissues were observed to follow approximately the defined collagen fibre directions

Prova 2

Issue 2 of PROVA: the annual RCA Humanities Research Forum Journal. The words ‘trial’, ‘attempt’ and ‘rehearsal’ are all definitions of the Italian word prova. In the language of bespoke shoemaking, the prova is the primary model around which leather and heel are moulded to make the shoe. Prova is a first, it was the first, and now it is also the second. If the first issue of the Prova Journal was a giro di prova (a test or trial run), and in prova (on probation), this second issue represents another attempt, fino a prova contraria (until [it is] proven otherwise)

Understanding key parameters affecting needle-free skin penetration by a parenteral drug delivery system

This thesis seeks to resolve difficulties in the development of a parenteral needle-free drug delivery system. Analysis of the penetration performance of Glide Pharma’s Solid Dose Injector in two clinical trials on man has shown that skin, and likely its inherent variation, was the cause of incomplete deliveries. As indicated by the literature and issues with previous needle-free technologies, a more complete understanding of skin penetration is required before such systems are capable of ensuring delivery across a patient population. Exploratory skin experiments led to the justification, design and build of a novel skin penetration test rig capable of simulating the delivery of a solid dose implant. This test rig, the Penetrometer, required significant software development to both stabilise and validate its performance before use on the in vivo porcine model, an established non-clinical model for drug delivery through human skin. Two non-clinical studies have been performed using the Penetrometer to capture force displacement profiles, using a metal probe equivalent to an implant, for penetration events on multiple test sites on multiple models. Significant levels of variation in key parameters were shown to be present intra- and inter-test site, as well as intra- and inter-model. It is likely that this variation, as detected in the porcine model, was the cause of problematic system performance during human clinical trials. Penetration experiments have also been performed to establish the validity of using in vitro skin or silicone rubber as an alternative test bed to in vivo models. The key parameters measured are the peak force during penetration, the displacement of the skin at penetration and the work required to penetrate the skin, with variations observed of the order of 30%, 100% and 140%, respectively. The results indicate how challenging it will be to reliably administer drugs using needle-free injection. This information should be used to better specify the device design and implant formulation to ensure delivery success. Prior to this thesis there was no quantitative data available, either published or within the collaborator, describing the magnitude and variation of the key parameters affecting needle-free skin penetration. This thesis has used the porcine model, further work must determine the parameters for the breadth of a human patient population

The Neolithic of Central and Northwestern Anatolia, Thrace and its relations with Southeastern Europe

Ankara : The Department of Archaeology and History of Art, and Institute of Economics and Social Sciences of Bilkent Univ., 2000.Thesis (Master's) -- Bilkent University, 2000.Includes bibliographical references leaves 94-115.In this thesis, I intend to focus on the Neolithic of North-West Anatolia. Thanks to recent research activities by M.Özdoğan (1997; 1998c& d; 1999b), T. Efe (1995, 2000) and J. J. Roodenberg (1995a& b; 2000a& b) it is now possible to define a North-West Anatolian Neolithic. With such a definition, it will be possible to decide whether this néolithisation can be understood as an autonomous development or as a consequence of diffusion from another place most probably from the Near East. It is also aimed to present a clearer chronology, which is most needed at this stage of researches. As a base for the discussion, a thorough synthesis of the development in architecture and pottery will be presented.^ Other groups of material culture will be used in a selective way, in order to emphasise relationships, since a full discussion is beyond the limits of M.A. thesis. The area covered comprises Central Anatolia (Can Hasan III, Suberde Musular, Erbaba, Köşk Höyük), the Lake District (Hacılar, Bademağacı, Höyücek and Kuruçay), Marmara (Ihpınar, Fikirtepe and Pendik) and Turkish Thrace (Hoca Çeşme, Aşağı Pınar and Yarımburgaz). It will allow a general description of the cultural and chronological development of the North-West Anatolian Neolithic, its long distance contacts and its cultural connections. A comparison between the North-West Anatolian Neolithic and the Neolithic cultures of neighbouring regions, especially the Balkans and Central Anatolia will help to understand mutual relationships between these areas. In the conclusion, the néolithisation process in the Marmara and Turkish Thrace and its relations with the neighbouring regions will be evaluated.Arıkan, BülentM.S

Optogenetics in striated muscle: defibrillation of the heart and direct stimulation of skeletal muscles with light

Optogenetic depolarization of cells using the non-selective cation channel Channelrhodopsin-2 (ChR2) enables precise control over the membrane potential of cells within a specific area of intact organs. Furthermore, the selective overexpression of light-gated proteins allows cell type-specific and pain-free stimulation which could be of great benefit for future scientific and therapeutic approaches. In my thesis, I explored two potential applications of optogenetic methods in striated muscle: optogenetic defibrillation to terminate ventricular arrhythmia in intact mouse hearts and direct optogenetic stimulation of skeletal muscles. These new approaches could lead in the future to the development of optogenetic defibrillators and laryngeal pacemakers. Most experiments were performed with explanted hearts, isolated skeletal fibers and muscles or larynges from transgenic ChR2 expressing mice. To add translational perspectives, we also explored optogenetic defibrillation and intralaryngeal muscles stimulation after ChR2 gene transfer to wild type mice using adeno-associated virus (AAV). Optogenetic defibrillation by epicardial illumination was highly efficient in terminating ventricular arrhythmia in transgenic hearts and the success rate of optogenetic defibrillation was depending on the pulse duration, the size of illumination and the light intensity. Importantly, we were also able to terminate ventricular arrhythmia in non-transgenic hearts even one year after AAV mediated gene transfer. The potential applicability of optogenetic defibrillation in the human heart was assessed in experimentally-calibrated computer simulations of a patient’s heart with infarct-related ventricular tachycardia. Because optogenetic stimulation would be in principle pain-free in patients, the proof for its feasibility could lay the foundation for the development of a new treatment option for patients at high risk for ventricular arrhythmia. Direct optogenetic stimulation of skeletal muscle was first proven in isolated Flexor digitorum brevis fibers and in intact soleus muscles, which could both be stimulated using brief light pulses. The force of light-induced single twitches could be precisely controlled by varying the pulse duration and light intensity. Optogenetic stimulation was most efficient with 10 ms long pulses at a repetition rate of 40 Hz reaching ~84% of the maximum force generated by electrical stimulation with 100 Hz. Recurrent nerve paralysis is a severe complication of neck surgery, malignant processes or central neurological diseases and results in a fixed paramedian position of the vocal cords as well as life-threatening dyspnea in the case of bilateral paralysis. Current treatment options consist only of destructive surgery. Unfortunately the use of local electrical stimulation to restore laryngeal function faces severe technical limitations. Therefore I sought to explore direct optogenetic stimulation of intralaryngeal muscles in explanted larynges from ChR2 transgenic mice. Specific illumination of the individual intralaryngeal muscle groups led to an opening or closing of the vocal cords depending on the site of illumination. This proves the sufficient spatial resolution of light for selective stimulation of the intralaryngeal muscles groups. In addition, we were able to induce opening of the vocal cords in wild type mice after AAV-based gene transfer of ChR2 with light. Thus optogenetic stimulation could become a new treatment option for patients suffering from bilateral laryngeal paralysis. In conclusion, optogenetic stimulation can overcome the severe limitations of electrical stimulation of the heart and skeletal muscles. The new technologies, I have developed and characterized in this thesis, allow for the design of completely new stimulation patterns to address open questions in muscle physiology. Furthermore, optogenetic stimulation of striated muscles could become a new treatment option for patients enabling selective and pain-free stimulation with few side effects

A comprehensive approach towards the phylogeny and evolution of cervidae

Cervidae (deer) belong to Ruminantia together with Tragulidae (chevrotains), Antilocapridae (pronghorns), Moschidae (musk deer), Giraffidae (giraffes), and Bovidae (cattle, sheep, antelopes). After bovids, cervids are the second most diverse group of ruminants and large herbivores in general. Cervids are natively distributed in the Americas, Europe and Asia inhabiting a broad variety of habitats. Antlers, deciduous, osseous branched outgrowths of the frontal bone, are synapomorphic for all living member of Cervidae except for the Chinese water deer, Hydropotes inermis, in which they have presumably been lost. They are unique cranial appendages, which are shed and rebuilt at intervals. The antlerogenic process is controlled by a complex interaction of fluctuating levels of several hormones, most importantly testosterone. The oldest antler remains are recorded from the early Miocene. These have often been interpreted as non-deciduous appendages in the past, because of supposed permanent skin coverage and the lack of a burr. Extensive comparative morphological analyses of external features of the antler and of the abscission area showed that antlers of all extant and of eight Miocene cervid genera, including those of most of the earliest cervids Procervulus, Ligeromeryx, and Lagomeryx were deciduous. This insight is particularly important for the systematic classification of early Miocene species as Cervidae, because the absence of antler shedding and rebuilding would exclude them from the total group Cervidae. Cervid systematics has been puzzling researchers for over 150 years. The initial, gross (sub)classifications based on morphology and comparative anatomy are mostly supported by molecular data. In recent decades, molecular systematics has provided new input, but consensus could only be partially reached. Cervids are traditionally subdivided into two subfamilies, Cervinae, consisting of Muntiacini and Cervini, and Capreolinae, consisting of Alceini, Capreolini, Odocoileini, and Rangiferini. While the systematic relationships within Muntiacini and Cervini are, with very few exceptions, resolved, systematic relationships within Capreolinae are much more controversial. The position of Capreolini and Alceini is uncertain and there are many polyphylies within Odocoileini. The latter is the youngest clade of cervids with a quick diversification rate, which makes resolving the systematic relationships more difficult. Also, the rich fossil record of cervids has never been extensively phylogenetically tested concerning potential systematic relationships of fossil representatives to extant cervid taxa. The aim of this work was to investigate the systematic relationships of extant and fossil cervids using molecular and morphological characters and make implications about their evolutionary history based on the phylogenetic reconstructions. To achieve these objectives, molecular data were compiled primarily from public data bases such as GenBank. Some cervid species still lack molecular data because they are difficult to access in the wild. In order to complement the existing data, partial mitochondrial cytochrome b gene sequences from museum specimens of five previously unrecorded species were extracted. The resulting data set was so far the most extensive concerning the taxon sampling for cervids. All molecular data were combined to a data set including 17709 base pairs across five nuclear markers and the complete mitochondrial genome of 50 extant and one fossil cervid species. Several analyses using different data partitions, taxon sampling, partitioning schemes, and optimality criteria were undertaken. Divergence time estimates were undertaken on the molecular data sets using molecular clock node dating. Additionally, the most extensive morphological character matrix for such a broad cervid taxon sampling was compiled. In total 168 cranial and dental characters of 41 extant and 29 fossil cervid species were scored. Due to the highly conservative morphological features of cervids, solving systematic relationships was challenging for both extant and fossil species. However, it was possible to determine several characters useful to diagnose cervid subclades. The morphological and molecular data were combined for a total evidence approach and other phylogenetic testing. A tip dating analyses was also undertaken on the total evidence data set. Molecular topologies were partially in conflict with morphological topologies. Nuclear topologies suggested different systematic relationships for some taxa than the mitochondrial topologies. The combined molecular analyses provided robust topologies. The total evidence analyses were less robust and still contained large areas of unresolved taxa. Alternative approaches to combine both data sets and fossil and extant taxa were more useful. The two different divergence time estimate approaches provided differing but feasible results for each approach. The results showed that most of the Miocene cervids were considered to be more closely related to each other than to any other cervid. They were positioned either between the outgroup and all other cervids or as the sister taxon to Muntiacini. Two Miocene cervids were frequently placed within Muntiacini. Plio- and Pleistocene cervids could often be affiliated to Cervini, Odocoileini or Capreolini. Their morphology is more similar to extant cervids than the morphology of most Miocene cervids. The phylogenetic analyses of this work provide new insights into the evolutionary history of cervids. New systematic relationships were observed, some uncertainties persist and resolving phylogenetic relationships within certain taxa remain challenging. The analyses on the extensive data sets presented here concretised systematic problems and uncertainties, which can now better be targeted with phylogenetic approaches. Several fossil cervids could be successfully related to living representatives, confirming previously assumed affiliations based on qualitative comparisons and introducing new hypotheses. Cervid systematics remains an interesting and fascinating area of research with exciting new results to be expected in the future