Irradiation, cisplatin, and 5-azacytidine upregulate cytomegalovirus promoter in tumors and muscles: Implementation of non-invasive fluorescence imaging

Purpose: The cytomegalovirus (CMV) promoter is one of the most commonly used promoters for expression of transgenes in mammalian cells. The aim of our study was to evaluate the role of methylation and upregulation of the CMV promoter by irradiation and the chemotherapeutic agent cisplatin in vivo using non-invasive fluorescence in vivo imaging. Procedures: Murine fibrosarcoma LPB and mammary carcinoma TS/A cells were stably transfected with plasmids encoding CMV and p21 promoter-driven green fluorescent protein (GFP) gene. Solid TS/A tumors were induced by subcutaneous injection of fluorescent tumor cells, while leg muscles were transiently transfected with plasmid encoding GFP under the control of the CMV promoter. Cells, tumors, and legs were treated either by DNA methylation inhibitor 5-azacytidine, irradiation, or cisplatin. GFP expression was determined using a fluorescence microplate reader in vitro and by non-invasive fluorescence imaging in vivo. Results: Treatment of cells, tumors, and legs with 5-azacytidine (re)activated the CMV promoter. Furthermore, treatment with irradiation or cisplatin resulted in significant upregulation of GFP expression both in vitro and in vivo. Conclusions: Observed alterations in the activity of the CMV promoter limit the usefulness of this widely used promoter as a constitutive promoter. On the other hand, inducibility of CMV promoters can be beneficially used in gene therapy when combined with standard cancer treatment, such as radiotherapy and chemotherapy. © 2010 The Author(s).

Intervertebral staple grading system with micro-CT

Introduction Intervertebral stapling is a leading method of fusionless scoliosis treatment which attempts to control growth by applying pressure to the convex side of a scoliotic curve in accordance with the Hueter-Volkmann principle. In addition to that, staples have the potential to damage surrounding bone during insertion and subsequent loading. The aim of this study was to assess the extent of bony structural damage including epiphyseal injury as a result of intervertebral stapling using an in vitro bovine model. Materials and Methods Thoracic spines from 6-8 week old calves were dissected and divided into motion segments including levels T4-T11 (n=14). Each segment was potted in polymethylemethacrylate. An Instron Biaxial materials testing machine with a custom made jig was used for testing. The segments were tested in flexion/extension, lateral bending and axial rotation at 37⁰C and 100% humidity, using moment control to a maximum 1.75 Nm with a loading rate of 0.3 Nm per second for 10 cycles. The segments were initially tested uninstrumented with data collected from the tenth load cycle. Next an anterolateral 4-prong Shape Memory Alloy (SMA) staple (Medtronic Sofamor Danek, USA) was inserted into each segment. Biomechanical testing was repeated as before. The staples were cut in half with a diamond saw and carefully removed. Micro-CT scans were performed and sagittal, transverse and coronal reformatted images were produced using ImageJ (NIH, USA).The specimens were divided into 3 grades (0, 1 and 2) according to the number of epiphyses damaged by the staple prongs. Results: There were 9 (65%) segments with grade 1 staple insertions and 5 (35%) segments with grade 2 insertions. There were no grade 0 staples. Grade 2 spines had a higher stiffness level than grade 1 spines, in all axes of movement, by 28% (p=0.004). This was most noted in flexion/extension with an increase of 49% (p=0.042), followed by non-significant change in lateral bending 19% (p=0.129) and axial rotation 8% (p=0.456) stiffness. The cross sectional area of bone destruction from the prongs was only 0.4% larger in the grade 2 group compared to the grade 1 group (p=0.961). Conclusion Intervertebral staples cause epiphyseal damage. There is a difference in stiffness between grade 1 and grade 2 staple insertion segments in flexion/extension only. There is no difference in the cross section of bone destruction as a result of prong insertion and segment motion.

Contactless and replaceable modularized battery energy storage system for electric vehicles

A novel replaceable, modularized energy storage system with wireless interface is proposed for a battery operated electric vehicle (EV). The operation of the proposed system is explained and analyzed with an equivalent circuit and an averaged state-space model. A non-linear feedback linearization based controller is developed and implemented to regulate the DC link voltage by modulating the phase shift ratio. The working and control of the proposed system is verified through simulation and some preliminary results are presented.

Grid-side cascade inverter system as an interface for wind energy storage

Additional converters that are used to interface energy storage devices incur power losses as well as increased system cost and complexity. The need for additional converters can be eliminated if the grid side inverter can itself be effectively used as the interface for energy storage. This paper therefore proposes a technique whereby the grid side inverter can also be used as an interface to connect a supercapacitor energy storage for wind energy conversion systems. The proposed grid side inverter is formed by cascading a 3-level inverter and a 2-level inverter through a coupling transformer. The three-level inverter is the main inverter and it is powered by the rectified output of the wind turbine coupled AC generator while the 2-level auxiliary inverter is connected to the super capacitor bank that is used to compensate short term power fluctuations. Novel modulation and control techniques are proposed to address the problems associated with non-integer and dynamically-changing dc-link voltage ratio, which is caused by the random nature of wind. Simulation results are presented to verify the efficacy of the proposed system in suppressing short term wind power fluctuations.

The technical efficiency of the Japanese banks : non-radial directional performance measurement with undesirable output

The paper analyses technical efficiency of the Japanese banks from 2000 to 2007. The estimation technique is based on the Russell directional distance function that takes into consideration not only desirable outputs but also an undesirable output that is represented by non-performing loans (NPLs). The results indicate that NPLs remain a significant burden as for banks' performance. We show that banks' inputs have to be utilised more efficiently, particularly labour and premises. We also argue that a further restructuring process is needed in the segment of Regional Banks. We conclude that the Japanese banking system is still far away from being fully consolidated and restructured.

Enhancing interdisciplinary learning with a learning management system

Interdisciplinary learning is a form of knowledge production that is increasingly being embraced as an educational approach in higher education. A role of information and communication technologies (ICT) is to enhance interdisciplinary learning. Issues surrounding the mix of interdisciplinary pedagogic methodologies and emerging digital technologies are worthy of investigation. In this paper, the authors report the findings of a study that examined student perceptions of an interdisciplinary course on information technology (IT) and visual design that utilized a learning management system. Using questionnaire instrumentation, the authors sought the perceptions of first-year university students enrolled in a newly formed interdisciplinary IT course. Results indicate that ICT-based interdisciplinary learners prefer a self-directed and collaborative instructional modality, as well as teacher presence and interventions in the online environment. The types of student participation can significantly influence how students perceive ICT-based interdisciplinary learning design.

Dual inverter based battery energy storage system for grid connected photovoltaic systems

This paper explores a new breed of energy storage system interfacing for grid connected photovoltaic (PV) systems. The proposed system uses the popular dual inverter topology in which one inverter is supplied by a PV cell array and the other by a Battery Energy Storage System (BESS). The resulting conversion structure is controlled in a way that both demand matching and maximum power point tracking of the PV cell array are performed simultaneously. This dual inverter topology can produces 2, 3, 4 and 5 level inverter voltage waveforms at the dc-link voltage ratios of 0:1, 1:1, 2:1 and 3:2 respectively. Since the output voltage of the PV cell array and the battery are uncorrelated and dynamically change, the resulting dc-link voltage ratio can take non-integer values as well. These noninteger dc-link voltage ratios produce unevenly distributed space vectors. Therefore, the main issue with the proposed system is the generation of undistorted current even in the presence of unevenly distributed and dynamically changing space vectors. A modified space vector modulation method is proposed in this paper to address this issue and its efficacy is proved by simulation results. The ability of the proposed system to act as an active power source is also verified.

Visual function and the ageing visual system

The population is ageing. Globally, the number of older adults (aged 60 years or over) is expected to more than double, from 841 million people in 2013 to more than 2 billion in 2050.1 In light of the increasing size of the older adult population, there is a pressing need to better identify the nature of, and mechanisms underlying, age-related vision impairment and the functional impact it has on the performance of everyday activities in older adults. The content of this feature issue reflects the diversity of research currently being undertaken on the topic of the ageing visual system and the important visual challenges that this presents for our ageing patient population. The scope is broad and includes topics relating to three main related themes: 1) The treatment of age-related ocular disorders and diseases and their consequences, including presbyopia and AMD; 2) The impact of age-related visual changes on everyday activities in older people, including mobility, driving and falls, and; 3) The interaction of age-related visual impairments and other age-related impairments including hearing and cognitive changes.

Geochemistry-based coral palaeoclimate studies and the potential of ‘non-traditional’ (non-massive Porites) corals : recent developments and future progression

Understanding the natural variability of the Earth's climate system and accurately identifying potential anthropogenic influences requires long term, geographically distributed records of key climate indicators, such as temperature and precipitation that extend prior to the last 400. years of the Holocene. Reef corals provide an excellent source of high resolution climate records, and importantly represent the tropical marine environment where palaeoclimate data are urgently required. Recent decades have seen significant improvement in our understanding of coral biomineralisation, the associated uptake of geochemical proxies and methods of identifying and understanding the effects of both early and late, post depositional diagenetic alteration. These processes all have significant implications for interpreting geochemical proxies relevant to palaeoclimatic reconstructions. This paper reviews the current 'state of the art' in terms of coral based palaeoclimate reconstructions and highlights a key remaining problem. The majority of coral based palaeoclimate research has been derived from massive colonies of Porites. However, massive Porites are not globally abundant and may not provide material of a particular age of interest in those regions where they are present. Therefore, there is great potential for alternate coral genera to act as complimentary climate archives. While it remains critical to consider five key factors - vital effects, differential growth morphologies, geochemical heterogeneity in the skeletal ultrastructure, transfer equation selection and diagenetic screening of skeletal material - in order to allow the highest level of accuracy in coral palaeoclimate reconstructions, it is also important to develop alternate taxa for palaeoclimate studies in regions where Porites colonies are absent or rare. Currently as many as nine genera other than Porites have proven at least limited utility in palaeothermometry, most of which are found in the Atlantic/Caribbean region where massive Porites do not exist. Even branching taxa such as Acropora have significant potential to preserve environmental archives. Increasing this capability will greatly expand the number of potential geochemical archives available for longer term temporal records of palaeoclimate.

Non-destructive DNA extraction from Chironomidae, including of fragile pupal exuviae, extends analysable collections and enhances vouchering

It is well established that the traditional taxonomy and nomenclature of Chironomidae relies on adult males whose usually characteristic genitalia provide evidence of species distinction. In the early days some names were based on female adults of variable distinctiveness – but females are difficult to identify (Ekrem et al. 2010) and many of these names remain dubious. In Russia especially, a system based on larval morphology grew in parallel to the conventional adult-based system. The systems became reconciled with the studies that underlay the production of the Holarctic generic keys to Chironomidae, commencing notably with the larval volume (Wiederholm, 1983). Ever since Thienemann’s pioneering studies, it has been evident that the pupa, notably the cast skins (exuviae) provide a wealth of features that can aid in identification (e.g. Wiederholm, 1986). Furthermore, the pupae can be readily associated with name-bearing adults when a pharate (‘cloaked’) adult stage is visible within the pupa. Association of larvae with the name-bearing later stages has been much more difficult, time-consuming and fraught with risk of failure. Yet it is identification of the larval stage that is needed by most applied researchers due to the value of the immature stages of the family in aquatic monitoring for water quality, although the pupal stage also has advocates (reviewed by Sinclair & Gresens, 2008). Few use the adult stage for such purposes as their provenance and association with the water body can be verified only by emergence trapping, and sampling of adults lies outside regular aquatic monitoring protocols.

Locally weighted learning methods for non-rigid robot control

This thesis develops a novel approach to robot control that learns to account for a robot's dynamic complexities while executing various control tasks using inspiration from biological sensorimotor control and machine learning. A robot that can learn its own control system can account for complex situations and adapt to changes in control conditions to maximise its performance and reliability in the real world. This research has developed two novel learning methods, with the aim of solving issues with learning control of non-rigid robots that incorporate additional dynamic complexities. The new learning control system was evaluated on a real three degree-of-freedom elastic joint robot arm with a number of experiments: initially validating the learning method and testing its ability to generalise to new tasks, then evaluating the system during a learning control task requiring continuous online model adaptation.

Modelling busway operation with mixed stopping and non-stopping buses

This thesis investigated the complexity of busway operation with stopping and non-stopping buses using field data and microscopic simulation modelling. The proposed approach made significant recommendations to transit authorities to achieve the most practicable system capacity for existing and new busways. The empirical equations developed in this research and newly introduced analysis methods will be ideal tools for transit planners to achieve optimal reliability of busways.

Novel non-linear elastic structural analysis with generalised transverse element loads using a refined finite element

In the finite element modelling of structural frames, external loads such as wind loads, dead loads and imposed loads usually act along the elements rather than at the nodes only. Conventionally, when an element is subjected to these general transverse element loads, they are usually converted to nodal forces acting at the ends of the elements by either lumping or consistent load approaches. In addition, it is especially important for an element subjected to the first- and second-order elastic behaviour, to which the steel structure is critically prone to; in particular the thin-walled steel structures, when the stocky element section may be generally critical to the inelastic behaviour. In this sense, the accurate first- and second-order elastic displacement solutions of element load effect along an element is vitally crucial, but cannot be simulated using neither numerical nodal nor consistent load methods alone, as long as no equilibrium condition is enforced in the finite element formulation, which can inevitably impair the structural safety of the steel structure particularly. It can be therefore regarded as a unique element load method to account for the element load nonlinearly. If accurate displacement solution is targeted for simulating the first- and second-order elastic behaviour on an element on the basis of sophisticated non-linear element stiffness formulation, the numerous prescribed stiffness matrices must indispensably be used for the plethora of specific transverse element loading patterns encountered. In order to circumvent this shortcoming, the present paper proposes a numerical technique to include the transverse element loading in the non-linear stiffness formulation without numerous prescribed stiffness matrices, and which is able to predict structural responses involving the effect of first-order element loads as well as the second-order coupling effect between the transverse load and axial force in the element. This paper shows that the principle of superposition can be applied to derive the generalized stiffness formulation for element load effect, so that the form of the stiffness matrix remains unchanged with respect to the specific loading patterns, but with only the magnitude of the loading (element load coefficients) being needed to be adjusted in the stiffness formulation, and subsequently the non-linear effect on element loadings can be commensurate by updating the magnitude of element load coefficients through the non-linear solution procedures. In principle, the element loading distribution is converted into a single loading magnitude at mid-span in order to provide the initial perturbation for triggering the member bowing effect due to its transverse element loads. This approach in turn sacrifices the effect of element loading distribution except at mid-span. Therefore, it can be foreseen that the load-deflection behaviour may not be as accurate as those at mid-span, but its discrepancy is still trivial as proved. This novelty allows for a very useful generalised stiffness formulation for a single higher-order element with arbitrary transverse loading patterns to be formulated. Moreover, another significance of this paper is placed on shifting the nodal response (system analysis) to both nodal and element response (sophisticated element formulation). For the conventional finite element method, such as the cubic element, all accurate solutions can be only found at node. It means no accurate and reliable structural safety can be ensured within an element, and as a result, it hinders the engineering applications. The results of the paper are verified using analytical stability function studies, as well as with numerical results reported by independent researchers on several simple frames.

Numerical simulation of railway track supporting system using finite-infinite and thin layer elements under impulsive loads

The present study deals with two dimensional, numerical simulation of railway track supporting system subjected to dynamic excitation force. Under plane strain condition, the coupled finite-infinite elements to represent the near and far field stress distribution and thin layer interface element was employed to model the interfacial behavior between sleepers and ballast. To account for the relative debonding, slipping and crushing that could take place in the contact area between the sleepers and ballast, modified Mohr-Coulomb criterion was adopted. Furthermore an attempt has been made to consider the elasto-plastic material non-linearity of the railway track supporting media by employing different constitutive models to represent steel, concrete and supporting materials. Based on the proposed physical and constitutive modeling a code has been developed for dynamic loads. The applicability of the developed F.E code has been demonstrated by analyzing a real railway supporting structure.