Photodynamic therapy: a new concept in medical treatment

A new concept in the therapy of both neoplastic and non-neoplastic diseases is discussed in this article. Photodynamic therapy (PDT) involves light activation, in the presence of molecular oxygen, of certain dyes that are taken up by the target tissue. These dyes are termed photosensitizers. The mechanism of interaction of the photosensitizers and light is discussed, along with the effects produced in the target tissue. The present status of clinical PDT is discussed along with the newer photosensitizers being used and their clinical roles. Despite the promising results from earlier clinical trials of PDT, considerable additional work is needed to bring this new modality of treatment into modern clinical practice. Improvements in the area of light source delivery, light dosimetry and the computation of models of treatment are necessary to standardize treatments and ensure proper treatment delivery. Finally, quality assurance issues in the treatment process should be introduced.

Immunophenotype of normal and leukemic bone marrow B-precursors in a Brazilian population. A comparative analysis by quantitative fluorescence cytometry

The distinction between normal and leukemic bone marrow (BM) B-precursors is essential for the diagnosis and treatment monitoring of acute lymphoblastic leukemia (ALL). In order to evaluate the potential use of quantitative fluorescence cytometry (QFC) for this distinction, we studied 21 normal individuals and 40 patients with CD10+ ALL. We characterized the age-related changes of the CD10, CD19, TdT, CD34 and CD79a densities in normal and leukemic BM. Compared to normal adults, the B-precursors from normal children expressed significantly lower values of CD34-specific antibody binding capacity (SABC) (median value of 86.6 vs 160.2 arbitrary units (a.u.) in children and adults, respectively). No significant age-related difference was observed in the expression of the other markers in the normal BM, or in any of the markers in the leukemic BM. Based on the literature, we set the cut-off value for the normal CD10 expression at 45 x 10³ a.u. for both age groups. For the remaining markers we established the cut-off values based on the minimum-maximum values in the normal BM in each age group. The expression of CD10 was higher than the cut-off in 30 ALL cases and in 18 of them there was a concomitant aberrant expression of other markers. In 9 of the 10 CD10+ ALL with normal CD10 SABC values, the expression of at least one other marker was aberrant. In conclusion, the distinction between normal and leukemic cells by QFC was possible in 38/40 CD10+ ALL cases.

Value of Information Logistics Integration in Digital Business Ecosystem

Digital business ecosystems (DBE) are becoming an increasingly popular concept for modelling and building distributed systems in heterogeneous, decentralized and open environments. Information- and communication technology (ICT) enabled business solutions have created an opportunity for automated business relations and transactions. The deployment of ICT in business-to-business (B2B) integration seeks to improve competitiveness by establishing real-time information and offering better information visibility to business ecosystem actors. The products, components and raw material flows in supply chains are traditionally studied in logistics research. In this study, we expand the research to cover the processes parallel to the service and information flows as information logistics integration. In this thesis, we show how better integration and automation of information flows enhance the speed of processes and, thus, provide cost savings and other benefits for organizations. Investments in DBE are intended to add value through business automation and are key decisions in building up information logistics integration. Business solutions that build on automation are important sources of value in networks that promote and support business relations and transactions. Value is created through improved productivity and effectiveness when new, more efficient collaboration methods are discovered and integrated into DBE. Organizations, business networks and collaborations, even with competitors, form DBE in which information logistics integration has a significant role as a value driver. However, traditional economic and computing theories do not focus on digital business ecosystems as a separate form of organization, and they do not provide conceptual frameworks that can be used to explore digital business ecosystems as value drivers—combined internal management and external coordination mechanisms for information logistics integration are not the current practice of a company’s strategic process. In this thesis, we have developed and tested a framework to explore the digital business ecosystems developed and a coordination model for digital business ecosystem integration; moreover, we have analysed the value of information logistics integration. The research is based on a case study and on mixed methods, in which we use the Delphi method and Internetbased tools for idea generation and development. We conducted many interviews with key experts, which we recoded, transcribed and coded to find success factors. Qualitative analyses were based on a Monte Carlo simulation, which sought cost savings, and Real Option Valuation, which sought an optimal investment program for the ecosystem level. This study provides valuable knowledge regarding information logistics integration by utilizing a suitable business process information model for collaboration. An information model is based on the business process scenarios and on detailed transactions for the mapping and automation of product, service and information flows. The research results illustrate the current cap of understanding information logistics integration in a digital business ecosystem. Based on success factors, we were able to illustrate how specific coordination mechanisms related to network management and orchestration could be designed. We also pointed out the potential of information logistics integration in value creation. With the help of global standardization experts, we utilized the design of the core information model for B2B integration. We built this quantitative analysis by using the Monte Carlo-based simulation model and the Real Option Value model. This research covers relevant new research disciplines, such as information logistics integration and digital business ecosystems, in which the current literature needs to be improved. This research was executed by high-level experts and managers responsible for global business network B2B integration. However, the research was dominated by one industry domain, and therefore a more comprehensive exploration should be undertaken to cover a larger population of business sectors. Based on this research, the new quantitative survey could provide new possibilities to examine information logistics integration in digital business ecosystems. The value activities indicate that further studies should continue, especially with regard to the collaboration issues on integration, focusing on a user-centric approach. We should better understand how real-time information supports customer value creation by imbedding the information into the lifetime value of products and services. The aim of this research was to build competitive advantage through B2B integration to support a real-time economy. For practitioners, this research created several tools and concepts to improve value activities, information logistics integration design and management and orchestration models. Based on the results, the companies were able to better understand the formulation of the digital business ecosystem and the importance of joint efforts in collaboration. However, the challenge of incorporating this new knowledge into strategic processes in a multi-stakeholder environment remains. This challenge has been noted, and new projects have been established in pursuit of a real-time economy.

Comparison of the quantitative competitive and semiquantitative RT-PCR methods for the determination of interferon-gamma mRNA levels in AIDS-free HIV-infected individuals

IFN-gamma mRNA expression was evaluated in nonstimulated peripheral blood mononuclear cells (PBMC) of HIV-infected and seronegative individuals using quantitative competitive and semiquantitative RT-PCR and the sensitivity of these methods was compared. A significant correlation was found between quantitative competitive and semiquantitative RT-PCR in samples of both HIV-seronegative (P = 0.004) and HIV-infected individuals (P = 0.0004). PBMC from HIV-infected individuals presented a remarkable increase of IFN-gamma mRNA expression, as determined by both types of RT-PCR methods. Semiquantitative RT-PCR even without an internal standard is also acceptable for measuring cytokine mRNA expression, but less reliable if small amounts are quantified. Moreover, we found that increased IFN-gammamRNA expression is independent of CD4+ cell count in AIDS-free HIV-infected patients.

Virtual Runtime Application Partitions for Resource Management in Massively Parallel Architectures

This thesis presents a novel design paradigm, called Virtual Runtime Application Partitions (VRAP), to judiciously utilize the on-chip resources. As the dark silicon era approaches, where the power considerations will allow only a fraction chip to be powered on, judicious resource management will become a key consideration in future designs. Most of the works on resource management treat only the physical components (i.e. computation, communication, and memory blocks) as resources and manipulate the component to application mapping to optimize various parameters (e.g. energy efficiency). To further enhance the optimization potential, in addition to the physical resources we propose to manipulate abstract resources (i.e. voltage/frequency operating point, the fault-tolerance strength, the degree of parallelism, and the configuration architecture). The proposed framework (i.e. VRAP) encapsulates methods, algorithms, and hardware blocks to provide each application with the abstract resources tailored to its needs. To test the efficacy of this concept, we have developed three distinct self adaptive environments: (i) Private Operating Environment (POE), (ii) Private Reliability Environment (PRE), and (iii) Private Configuration Environment (PCE) that collectively ensure that each application meets its deadlines using minimal platform resources. In this work several novel architectural enhancements, algorithms and policies are presented to realize the virtual runtime application partitions efficiently. Considering the future design trends, we have chosen Coarse Grained Reconfigurable Architectures (CGRAs) and Network on Chips (NoCs) to test the feasibility of our approach. Specifically, we have chosen Dynamically Reconfigurable Resource Array (DRRA) and McNoC as the representative CGRA and NoC platforms. The proposed techniques are compared and evaluated using a variety of quantitative experiments. Synthesis and simulation results demonstrate VRAP significantly enhances the energy and power efficiency compared to state of the art.

Forecasting financial weather - can we foresee market sentiment? Quantitative analysis of nodal prices in the New Zealand Electricity Spot Market

Time series of hourly electricity spot prices have peculiar properties. Electricity is by its nature difficult to store and has to be available on demand. There are many reasons for wanting to understand correlations in price movements, e.g. risk management purposes. The entire analysis carried out in this thesis has been applied to the New Zealand nodal electricity prices: offer prices (from 29 May 2002 to 31 March 2009) and final prices (from 1 January 1999 to 31 March 2009). In this paper, such natural factors as location of the node and generation type in the node that effects the correlation between nodal prices have been reviewed. It was noticed that the geographical factor affects the correlation between nodes more than others. Therefore, the visualisation of correlated nodes was done. However, for the offer prices the clear separation of correlated and not correlated nodes was not obtained. Finally, it was concluded that location factor most strongly affects correlation of electricity nodal prices; problems in visualisation probably associated with power losses when the power is transmitted over long distance.

Lightweight, liquid-cooled, direct-drive generator for highpower wind turbines: motivation, concept, and performance

Thesis: A liquid-cooled, direct-drive, permanent-magnet, synchronous generator with helical, double-layer, non-overlapping windings formed from a copper conductor with a coaxial internal coolant conduit offers an excellent combination of attributes to reliably provide economic wind power for the coming generation of wind turbines with power ratings between 5 and 20MW. A generator based on the liquid-cooled architecture proposed here will be reliable and cost effective. Its smaller size and mass will reduce build, transport, and installation costs. Summary: Converting wind energy into electricity and transmitting it to an electrical power grid to supply consumers is a relatively new and rapidly developing method of electricity generation. In the most recent decade, the increase in wind energy’s share of overall energy production has been remarkable. Thousands of land-based and offshore wind turbines have been commissioned around the globe, and thousands more are being planned. The technologies have evolved rapidly and are continuing to evolve, and wind turbine sizes and power ratings are continually increasing. Many of the newer wind turbine designs feature drivetrains based on Direct-Drive, Permanent-Magnet, Synchronous Generators (DD-PMSGs). Being low-speed high-torque machines, the diameters of air-cooled DD-PMSGs become very large to generate higher levels of power. The largest direct-drive wind turbine generator in operation today, rated just below 8MW, is 12m in diameter and approximately 220 tonne. To generate higher powers, traditional DD-PMSGs would need to become extraordinarily large. A 15MW air-cooled direct-drive generator would be of colossal size and tremendous mass and no longer economically viable. One alternative to increasing diameter is instead to increase torque density. In a permanent magnet machine, this is best done by increasing the linear current density of the stator windings. However, greater linear current density results in more Joule heating, and the additional heat cannot be removed practically using a traditional air-cooling approach. Direct liquid cooling is more effective, and when applied directly to the stator windings, higher linear current densities can be sustained leading to substantial increases in torque density. The higher torque density, in turn, makes possible significant reductions in DD-PMSG size. Over the past five years, a multidisciplinary team of researchers has applied a holistic approach to explore the application of liquid cooling to permanent-magnet wind turbine generator design. The approach has considered wind energy markets and the economics of wind power, system reliability, electromagnetic behaviors and design, thermal design and performance, mechanical architecture and behaviors, and the performance modeling of installed wind turbines. This dissertation is based on seven publications that chronicle the work. The primary outcomes are the proposal of a novel generator architecture, a multidisciplinary set of analyses to predict the behaviors, and experimentation to demonstrate some of the key principles and validate the analyses. The proposed generator concept is a direct-drive, surface-magnet, synchronous generator with fractional-slot, duplex-helical, double-layer, non-overlapping windings formed from a copper conductor with a coaxial internal coolant conduit to accommodate liquid coolant flow. The novel liquid-cooling architecture is referred to as LC DD-PMSG. The first of the seven publications summarized in this dissertation discusses the technological and economic benefits and limitations of DD-PMSGs as applied to wind energy. The second publication addresses the long-term reliability of the proposed LC DD-PMSG design. Publication 3 examines the machine’s electromagnetic design, and Publication 4 introduces an optimization tool developed to quickly define basic machine parameters. The static and harmonic behaviors of the stator and rotor wheel structures are the subject of Publication 5. And finally, Publications 6 and 7 examine steady-state and transient thermal behaviors. There have been a number of ancillary concrete outcomes associated with the work including the following. X Intellectual Property (IP) for direct liquid cooling of stator windings via an embedded coaxial coolant conduit, IP for a lightweight wheel structure for lowspeed, high-torque electrical machinery, and IP for numerous other details of the LC DD-PMSG design X Analytical demonstrations of the equivalent reliability of the LC DD-PMSG; validated electromagnetic, thermal, structural, and dynamic prediction models; and an analytical demonstration of the superior partial load efficiency and annual energy output of an LC DD-PMSG design X A set of LC DD-PMSG design guidelines and an analytical tool to establish optimal geometries quickly and early on X Proposed 8 MW LC DD-PMSG concepts for both inner and outer rotor configurations Furthermore, three technologies introduced could be relevant across a broader spectrum of applications. 1) The cost optimization methodology developed as part of this work could be further improved to produce a simple tool to establish base geometries for various electromagnetic machine types. 2) The layered sheet-steel element construction technology used for the LC DD-PMSG stator and rotor wheel structures has potential for a wide range of applications. And finally, 3) the direct liquid-cooling technology could be beneficial in higher speed electromotive applications such as vehicular electric drives.

The Concept of Betterness and Sport Competitions

It is common that people disagree on a question which athlete or team was the best in a particular sport competition. This thesis attempts to clarify these disputes by analysing the concept of betterness in the context of sport competitions. Betterness can be interpersonal, intrapersonal or a combination of the two. I focus on interpersonal betterness, that is, on superiority. For example, interpersonal betterness may be contested in a football match between the national teams of Germany and Argentina. My aim is to provide a philosophical account of interpersonal betterness. The account has two functions: descriptive and normative. It describes the shapes and forms in which superiority is instantiated in sport competitions. It also provides a consistent and accurate way to discuss superiority. The thesis consists of two parts. In the first part, I introduce, elaborate and illustrate my account, which in turn consists of three elements: (1) relations of superiority, (2) standards for the relations of superiority and (3) types of competition. I also discuss my account’s relevance to issues of sport ethics through the example of gender equity and women’s ski jumping. I conclude that this account will not end the disputes over which team or athlete was better in a particular competition. Instead, it provides tools for a more consistent discussion of the disputed issues. The second part of the thesis includes five reprinted original articles. The account presented in the first part is based on these publications.

Comparison of the homeostasis model assessment and quantitative insulin sensitivity check index with data from forearm metabolic studies for the in vivo assessment of insulin sensitivity

The present study was designed to compare the homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) with data from forearm metabolic studies of healthy individuals and of subjects in various pathological states. Fifty-five healthy individuals and 112 patients in various pathological states, including type 2 diabetes mellitus, essential hypertension and others, were studied after an overnight fast and for 3 h after ingestion of 75 g of glucose, by HOMA, QUICKI and the forearm technique to estimate muscle uptake of glucose combined with indirect calorimetry (oxidative and non-oxidative glucose metabolism). The patients showed increased HOMA (1.88 ± 0.14 vs 1.13 ± 0.10 pmol/l x mmol/l) and insulin/glucose (I/G) index (1.058.9 ± 340.9 vs 518.6 ± 70.7 pmol/l x (mg/100 ml forearm)-1), and decreased QUICKI (0.36 ± 0.004 vs 0.39 ± 0.006 (µU/ml + mg/dl)-1) compared with the healthy individuals. Analysis of the data for the group as a whole (patients and healthy individuals) showed that the estimate of insulin resistance by HOMA was correlated with data obtained in the forearm metabolic studies (glucose uptake: r = -0.16, P = 0.04; non-oxidative glucose metabolism: r = -0.20. P = 0.01, and I/G index: r = 0.17, P = 0.03). The comparison of QUICKI with data of the forearm metabolic studies showed significant correlation between QUICKI and non-oxidative glucose metabolism (r = 0.17, P = 0.03) or I/G index (r = -0.37, P < 0.0001). The HOMA and QUICKI are good estimates of insulin sensitivity as data derived from forearm metabolic studies involving direct measurements of insulin action on muscle glucose metabolism.

Quantitative evidence for neurofilament heavy subunit aggregation in motor neurons of spinal cords of patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of unknown etiology, affects motor neurons leading to atrophy of skeletal muscles, paralysis and death. There is evidence for the accumulation of neurofilaments (NF) in motor neurons of the spinal cord in ALS cases. NF are major structural elements of the neuronal cytoskeleton. They play an important role in cell architecture and differentiation and in the determination and maintenance of fiber caliber. They are composed of three different polypeptides: light (NF-L), medium (NF-M) and heavy (NF-H) subunits. In the present study, we performed a morphological and quantitative immunohistochemical analysis to evaluate the accumulation of NF and the presence of each subunit in control and ALS cases. Spinal cords from patients without neurological disease and from ALS patients were obtained at autopsy. In all ALS cases there was a marked loss of motor neurons, besides atrophic neurons and preserved neurons with cytoplasmic inclusions, and extensive gliosis. In control cases, the immunoreaction in the cytoplasm of neurons was weak for phosphorylated NF-H, strong for NF-M and weak for NF-L. In ALS cases, anterior horn neurons showed intense immunoreactivity in focal regions of neuronal perikarya for all subunits, although the difference in the integrated optical density was statistically significant only for NF-H. Furthermore, we also observed dilated axons (spheroids), which were immunopositive for NF-H but negative for NF-M and NF-L. In conclusion, we present qualitative and quantitative evidence of NF-H subunit accumulation in neuronal perikarya and spheroids, which suggests a possible role of this subunit in the pathogenesis of ALS.

Social class as a factor for the construction of a musician’s identity : The Musician’s social background and identity questionnaire (MSBIQ) – a cross-sectional comparative quantitative online survey research study of music students at two higher education institutions in Finland

There is currently little empirical knowledge regarding the construction of a musician’s identity and social class. With a theoretical framework based on Bourdieu’s (1984) distinction theory, Bronfenbrenner’s (1979) theory of ecological systems, and the identity theories of Erikson (1950; 1968) and Marcia (1966), a survey called the Musician’s Social Background and Identity Questionnaire (MSBIQ) is developed to test three research hypotheses related to the construction of a musician’s identity, social class and ecological systems of development. The MSBIQ is administered to the music students at Sibelius Academy of the University of Arts Helsinki and Helsinki Metropolia University of Applied Sciences, representing the ’highbrow’ and the ’middlebrow’ samples in the field of music education in Finland. Acquired responses (N = 253) are analyzed and compared with quantitative methods including Pearson’s chi-square test, factor analysis and an adjusted analysis of variance (ANOVA). The study revealed that (1) the music students at Sibelius Academy and Metropolia construct their subjective musician’s identity differently, but (2) social class does not affect this identity construction process significantly. In turn, (3) the ecological systems of development, especially the individual’s residential location, do significantly affect the construction of a musician’s identity, as well as the age at which one starts to play one’s first musical instrument. Furthermore, a novel finding related to the structure of a musician’s identity was the tripartite model of musical identity consisting of the three dimensions of a musician’s identity: (I) ’the subjective dimension of a musician’s identity’, (II) ’the occupational dimension of a musician’s identity’ and, (III) ’the conservative-liberal dimension of a musician’s identity’. According to this finding, a musician’s identity is not a uniform, coherent entity, but a structure consisting of different elements continuously working in parallel within different dimensions. The results and limitations related to the study are discussed, as well as the objectives related to future studies using the MSBIQ to research the identity construction and social backgrounds of a musician or other performing artists.

Behavioral and physiological methods for early quantitative assessment of spinal cord injury and prognosis in rats

Methods for reliable evaluation of spinal cord (SC) injury in rats at short periods (2 and 24 h) after lesion were tested to characterize the mechanisms implicated in primary SC damage. We measured the physiological changes occurring after several procedures for producing SC injury, with particular emphasis on sensorimotor functions. Segmental and suprasegmental reflexes were tested in 39 male Wistar rats weighing 250-300 g divided into three control groups that were subjected to a) anesthesia, b) dissection of soft prevertebral tissue, and c) laminectomy of the vertebral segments between T10 and L1. In the lesion group the SC was completely transected, hemisected or subjected to vertebral compression. All animals were evaluated 2 and 24 h after the experimental procedure by the hind limb motility index, Bohlman motor score, open-field, hot-plate, tail flick, and paw compression tests. The locomotion scale proved to be less sensitive than the sensorimotor tests. A reduction in exploratory movements was detected in the animals 24 h after the procedures. The hot-plate was the most sensitive test for detecting sensorimotor deficiencies following light, moderate or severe SC injury. The most sensitive and simplest test of reflex function was the hot-plate. The hemisection model promoted reproducible moderate SC injury which allowed us to quantify the resulting behavior and analyze the evolution of the lesion and its consequences during the first 24 h after injury. We conclude that hemisection permitted the quantitation of behavioral responses for evaluation of the development of deficits after lesions. Hind limb evaluation scores and spontaneous exploration events provided a sensitive index of immediate injury effects after SC lesion at 2 and 24 h. Taken together, locomotion scales, open-field, and hot-plate tests represent reproducible, quantitatively sensitive methods for detecting functional deficiencies within short periods of time, indicating their potential for the study of cellular mechanisms of primary injury and repair after traumatic SC injury.

Effect of the Knowledge Representation Form on the Efficiency of Knowledge Sharing

The goal of this thesis is to estimate the effect of the form of knowledge representation on the efficiency of knowledge sharing. The objectives include the design of an experimental framework which would allow to establish this effect, data collection, and statistical analysis of the collected data. The study follows the experimental quantitative design. The experimental questionnaire features three sample forms of knowledge: text, mind maps, concept maps. In the interview, these forms are presented to an interviewee, afterwards the knowledge sharing time and knowledge sharing quality are measured. According to the statistical analysis of 76 interviews, text performs worse in both knowledge sharing time and quality compared to visualized forms of knowledge representation. However, mind maps and concept maps do not differ in knowledge sharing time and quality, since this difference is not statistically significant. Since visualized structured forms of knowledge perform better than unstructured text in knowledge sharing, it is advised for companies to foster the usage of these forms in knowledge sharing processes inside the company. Aside of performance in knowledge sharing, the visualized structured forms are preferable due the possibility of their usage in the system of ontological knowledge management within an enterprise.