Ultra-performance liquid chromatography mass spectrometry and sensitive bioassay methods for quantification of posaconazole plasma concentrations after oral dosing.

Posaconazole (POS) is a new antifungal agent for prevention and therapy of mycoses in immunocompromised patients. Variable POS pharmacokinetics after oral dosing may influence efficacy: a trough threshold of 0.5 ?g/ml has been recently proposed. Measurement of POS plasma concentrations by complex chromatographic techniques may thus contribute to optimize prevention and management of life-threatening infections. No microbiological analytical method is available. The objective of this study was to develop and validate a new simplified ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method and a sensitive bioassay for quantification of POS over the clinical plasma concentration range. The UPLC-MS/MS equipment consisted of a triple quadrupole mass spectrometer, an electrospray ionization (ESI) source, and a C(18) analytical column. The Candida albicans POS-hypersusceptible mutant (MIC of 0.002 ?g/ml) ?cdr1 ?cdr2 ?flu ?mdr1 ?can constructed by targeted deletion of multidrug efflux transporters and calcineurin genes was used for the bioassay. POS was extracted from plasma by protein precipitation with acetonitrile-methanol (75%/25%, vol/vol). Reproducible standard curves were obtained over the range 0.014 to 12 (UPLC-MS/MS) and 0.028 to 12 ?g/ml (bioassay). Intra- and interrun accuracy levels were 106% ± 2% and 103% ± 4% for UPLC-MS/MS and 102% ± 8% and 104% ± 1% for bioassay, respectively. The intra- and interrun coefficients of variation were 7% ± 4% and 7% ± 3% for UPLC-MS/MS and 5% ± 3% and 4% ± 2% for bioassay, respectively. An excellent correlation between POS plasma concentrations measured by UPLC-MS/MS and bioassay was found (concordance, 0.96). In 26 hemato-oncological patients receiving oral POS, 27/69 (39%) trough plasma concentrations were lower than 0.5 ?g/ml. The UPLC-MS/MS method and sensitive bioassay offer alternative tools for accurate and precise quantification of the plasma concentrations in patients receiving oral posaconazole.

Machine vision measurement system for paper printability assessments

This work had two primary objectives: 1) to produce a working prototype for automated printability assessment and 2) to perform a study of available machine vision and other necessary hardware solutions. The three printability testing methods, IGT Picking,He¬liotest, and mottling, considered in this work have several different requirements and the task was to produce a single automated testing system suitable for all methods. A system was designed and built and its performance was tested using the Heliotest. Working proto¬types are important tools for implementing theoretical methods into practical systems and testing and demonstrating the methodsin real life conditions. The system was found to be sufficient for the Heliotest method. Further testing and possible modifications related to other two test methods were left for future works. A short study of available systems and solutions concerning image acquisition of machine vision was performed. The theoretical part of this study includes lighting systems, optical systems and image acquisition tools, mainly cameras and the underlying physical aspects for each portion.

The Role and Measurement of Social Capital in New Technology-Based Start-up Context

Tämän Pro gradu-tutkielman tavoitteena olirakentaa esiymmärrys sosiaalisen pääoman roolista ja mittaamisesta uuden teknologian start-up yrityksissä. Pääasiallisena tarkoituksena tässä tutkimuksessa olilöytää sosiaalisen pääoman ja start-up yrityksen tuloksellisuuden välille yhdistävä tekijä. Tutkimuksen empiirinen aineisto kerättiin pääasiallisesti kuuden OKO Venture Capitalin sijoitusportfolioon sisältyvien case-yritysten kvalitatiivisten teemahaastatteluiden sekä kvantitatiivisten kyselylomakkeiden avulla. Kvalitatiivisten haastatteluiden tulosten perusteella sosiaalisen pääoman ja tuloksellisuuden välille löytyi yhdistävä tekijä, jota käytettiin myöhemmin hyväksi kvantitatiivisessa kyselylomakkeessa. Tämän tutkielman tulokset osoittivat, että startegisen päätöksenteon kautta sosiaalinen pääoma vaikuttaa osittain start-up yritysten tuloksellisuuteen. Manageriaalisesti tärkempi löydös tässä tutkimuksessa oli kuitenkin se, että sosiaalista pääomaa voidaan käyttää hyväksi ennustettaessa uuden teknologian start-up yritysten tulevaisuuden kassavirtoja.

A comparative performance study of four-pole induction motors and synchronous reluctance motors in variable speed drives

Design aspects of the Transversally Laminated Anisotropic (TLA) Synchronous Reluctance Motor (SynRM) are studied and the machine performance analysis compared to the Induction Motor (IM) is done. The SynRM rotor structure is designed and manufactured for a30 kW, four-pole, three-phase squirrel cage induction motor stator. Both the IMand SynRM were supplied by a sensorless Direct Torque Controlled (DTC) variablespeed drive. Attention is also paid to the estimation of the power range where the SynRM may compete successfully with a same size induction motor. A technicalloss reduction comparison between the IM and SynRM in variable speed drives is done. The Finite Element Method (FEM) is used to analyse the number, location and width of flux barriers used in a multiple segment rotor. It is sought for a high saliency ratio and a high torque of the motor. It is given a comparison between different FEM calculations to analyse SynRM performance. The possibility to take into account the effect of iron losses with FEM is studied. Comparison between the calculated and measured values shows that the design methods are reliable. A new application of the IEEE 112 measurement method is developed and used especially for determination of stray load losses in laboratory measurements. The study shows that, with some special measures, the efficiency of the TLA SynRM is equivalent to that of a high efficiency IM. The power factor of the SynRM at rated load is smaller than that of the IM. However, at lower partial load this difference decreases and this, probably, brings that the SynRM gets a better power factor in comparison with the IM. The big rotor inductance ratio of the SynRM allows a good estimating of the rotor position. This appears to be very advantageous for the designing of the rotor position sensor-less motor drive. In using the FEM designed multi-layer transversally laminated rotor with damper windings it is possible to design a directly network driven motor without degrading the motorefficiency or power factor compared to the performance of the IM.

Performance of an ultrasonic ranging sensor in apple tree canopies

Electronic canopy characterization is an important issue in tree crop management. Ultrasonic and optical sensors are the most used for this purpose. The objective of this work was to assess the performance of an ultrasonic sensor under laboratory and field conditions in order to provide reliable estimations of distance measurements to apple tree canopies. To this purpose, a methodology has been designed to analyze sensor performance in relation to foliage ranging and to interferences with adjacent sensors when working simultaneously. Results show that the average error in distance measurement using the ultrasonic sensor in laboratory conditions is ±0.53 cm. However, the increase of variability in field conditions reduces the accuracy of this kind of sensors when estimating distances to canopies. The average error in such situations is ±5.11 cm. When analyzing interferences of adjacent sensors 30 cm apart, the average error is ±17.46 cm. When sensors are separated 60 cm, the average error is ±9.29 cm. The ultrasonic sensor tested has been proven to be suitable to estimate distances to the canopy in field conditions when sensors are 60 cm apart or more and could, therefore, be used in a system to estimate structural canopy parameters in precision horticulture.

Aortic blood pressure measured via EIT: investigation of different measurement settings.

Electrical impedance tomography (EIT) allows the measurement of intra-thoracic impedance changes related to cardiovascular activity. As a safe and low-cost imaging modality, EIT is an appealing candidate for non-invasive and continuous haemodynamic monitoring. EIT has recently been shown to allow the assessment of aortic blood pressure via the estimation of the aortic pulse arrival time (PAT). However, finding the aortic signal within EIT image sequences is a challenging task: the signal has a small amplitude and is difficult to locate due to the small size of the aorta and the inherent low spatial resolution of EIT. In order to most reliably detect the aortic signal, our objective was to understand the effect of EIT measurement settings (electrode belt placement, reconstruction algorithm). This paper investigates the influence of three transversal belt placements and two commonly-used difference reconstruction algorithms (Gauss-Newton and GREIT) on the measurement of aortic signals in view of aortic blood pressure estimation via EIT. A magnetic resonance imaging based three-dimensional finite element model of the haemodynamic bio-impedance properties of the human thorax was created. Two simulation experiments were performed with the aim to (1) evaluate the timing error in aortic PAT estimation and (2) quantify the strength of the aortic signal in each pixel of the EIT image sequences. Both experiments reveal better performance for images reconstructed with Gauss-Newton (with a noise figure of 0.5 or above) and a belt placement at the height of the heart or higher. According to the noise-free scenarios simulated, the uncertainty in the analysis of the aortic EIT signal is expected to induce blood pressure errors of at least ± 1.4 mmHg.

Performance Evaluation of Imaging Systems

Imaging systems have developed latest years and developing is still continuing following years. Manufacturers of imaging systems give promises for the quality of the performance of imaging systems to advertise their products. Promises for the quality of the performance are often so good that they will not be tested in normal usage. The main target in this research is to evaluate the quality of the performance of two imaging systems: Scanner and CCD color camera. Optical measurement procedures were planned to evaluate the quality of imaging performances. Other target in this research is to evaluate calibration programs for the camera and the scanner. Measuring targets had to choose to evaluate the quality of imaging performances. Manufacturers have given definitions for targets. The third task in this research is to evaluate and consider how good measuring targets are.

Performance benchmarking and incentive regulation – considerations of directing signals for electricity distribution companies

After the restructuring process of the power supply industry, which for instance in Finland took place in the mid-1990s, free competition was introduced for the production and sale of electricity. Nevertheless, natural monopolies are found to be the most efficient form of production in the transmission and distribution of electricity, and therefore such companies remained franchised monopolies. To prevent the misuse of the monopoly position and to guarantee the rights of the customers, regulation of these monopoly companies is required. One of the main objectives of the restructuring process has been to increase the cost efficiency of the industry. Simultaneously, demands for the service quality are increasing. Therefore, many regulatory frameworks are being, or have been, reshaped so that companies are provided with stronger incentives for efficiency and quality improvements. Performance benchmarking has in many cases a central role in the practical implementation of such incentive schemes. Economic regulation with performance benchmarking attached to it provides companies with directing signals that tend to affect their investment and maintenance strategies. Since the asset lifetimes in the electricity distribution are typically many decades, investment decisions have far-reaching technical and economic effects. This doctoral thesis addresses the directing signals of incentive regulation and performance benchmarking in the field of electricity distribution. The theory of efficiency measurement and the most common regulation models are presented. The chief contributions of this work are (1) a new kind of analysis of the regulatory framework, so that the actual directing signals of the regulation and benchmarking for the electricity distribution companies are evaluated, (2) developing the methodology and a software tool for analysing the directing signals of the regulation and benchmarking in the electricity distribution sector, and (3) analysing the real-life regulatory frameworks by the developed methodology and further develop regulation model from the viewpoint of the directing signals. The results of this study have played a key role in the development of the Finnish regulatory model.

Merchandising Strategies and Retail Performance for Seasonal Fashion Products

This study presents mathematical methods for evaluation of retail performance with special regard to product sourcing strategies. Forecast accuracy, process lead time, offshore / local sourcing mix and up front / replenishment buying mix are defined as critical success factors in connection with sourcing seasonal products with a fashion content. As success measures, this research focuses on service level, lost sales, product substitute percentage, gross margin, gross margin return on inventory and mark down rate. The accuracy of demand forecast is found to be a fundamental success factor. Forecast accuracy depends on lead time. Lead times are traditionally long and buying decisions are made seven to eight months prior to the start of the selling season. Forecast errors cause stockouts and lost sales. Some of the products bought for the selling season will not be sold and have to be marked down and sold at clearance, causing loss of gross margin. Gross margin percentage is not the best tool for evaluating sourcing decisions and in the context of this study gross margin return on inventory, which combines profitability and assets management, is used. The findings of this research suggest that there are more profitable ways of sourcing products than buying them from low cost offshore sources. Mixing up front and inseason replenishment deliveries, especially when point of sale information is used for improving forecast accuracy, results in better retail performance. Quick Response and Vendor Managed Inventory strategies yield better results than traditional up front buying from offshore even if local purchase prices are higher. Increasing the number of selling seasons, slight over buying for the season in order to

IT architecture for category driven corporate procurement measurement

The purpose of this thesis was to investigate creating and improving category purchasing visibility for corporate procurement by utilizing financial information. This thesis was a part of the global category driven spend analysis project of Konecranes Plc. While creating general understanding for building category driven corporate spend visibility, the IT architecture and needed purchasing parameters for spend analysis were described. In the case part of the study three manufacturing plants of Konecranes Standard Lifting, Heavy Lifting and Services business areas were examined. This included investigating the operative IT system architecture and needed processes for building corporate spend visibility. The key findings of this study were the identification of the needed processes for gathering purchasing data elements while creating corporate spend visibility in fragmented source system environment. As an outcome of the study, roadmap presenting further development areas was introduced for Konecranes.

Performance Improvement of Centrifugal Compressor Stage with Pinched Geometry or Vaned Diffuser

Centrifugal compressors are widely used for example in refrigeration processes, the oil and gas industry, superchargers, and waste water treatment. In this work, five different vaneless diffusers and six different vaned diffusers are investigated numerically. The vaneless diffusers vary only by their diffuser width, so that four of the geometries have pinch implemented to them. Pinch means a decrease in the diffuser width. Four of the vaned diffusers have the same vane turning angle and a different number of vanes, and two have different vane turning angles. The flow solver used to solve the flow fields is Finflo, which is a Navier-Stokes solver. All the cases are modeled with the Chien's k – έ- turbulence model, and selected cases are modeled also with the k – ώ-SST turbulence model. All five vaneless diffusers and three vaned diffusers are investigated also experimentally. For each construction, the compressor operating map is measured according to relevant standards. In addition to this, the flow fields before and after the diffuser are measured with static and total pressure, flow angle and total temperature measurements. When comparing the computational results to the measured results, it is evident that the k – ώ-SST turbulence model predicts the flow fields better. The simulation results indicate that it is possible to improve the efficiency with the pinch, and according to the numerical results, the two best geometries are the ones with most pinch at the shroud. These geometries have approximately 4 percentage points higher efficiency than the unpinched vaneless diffusers. The hub pinch does not seem to have any major benefits. In general, the pinches make the flow fields before and after the diffuser more uniform. The pinch also seems to improve the impeller efficiency. This is down to two reasons. The major reason is that the pinch decreases the size of slow flow and possible backflow region located near the shroud after the impeller. Secondly, the pinches decrease the flow velocity in the tip clearance, leading to a smaller tip leakage flow and therefore slightly better impeller efficiency. Also some of the vaned diffusers improve the efficiency, the increment being 1...3 percentage points, when compared to the vaneless unpinched geometry. The measurement results confirm that the pinch is beneficial to the performance of the compressor. The flow fields are more uniform with the pinched cases, and the slow flow regions are smaller. The peak efficiency is approximately 2 percentage points and the design point efficiency approximately 4 percentage points higher with the pinched geometries than with the un- pinched geometry. According to the measurements, the two best geometries are the ones with the most pinch at the shroud, the case with the pinch only at the shroud being slightly better of the two. The vaned diffusers also have better efficiency than the vaneless unpinched geometries. However, the pinched cases have even better efficiencies. The vaned diffusers narrow the operating range considerably, whilst the pinch has no significant effect on the operating range.

Developing the Sourcing with the Purchasing Tool in the Chemical Company

The aim of this research was to investigate Tikkurila Oyj's Vantaa factories' current status in procurement and to develop the reporting of purchases and purchase warehouses, and to measure the activities during the implementation of the new purchasing tool. The implemented purchasing tool was based on ABC-analysis. Based on its reports the importance of performance measurements for the operations of the company, and the purpose of getting transparency to the company's supply chain on the part of purchasing were examined. A successful purchase- and material operation calls for accurate knowledge and professional skills. The research proved that with a separate purchasing tool, that analyses the existing information of the company's production management system, it is possible to get added value to whole supply chain's needs. The analyses and reports of the purchasing tool enable a more harmonized purchasing process at the operative level, and create a basis for internal targets and to their follow-up. At the same time the analyses clarify the current status and development trends of procurement fresh to the management. The increase of the possibilities of exploitation of information technology enables a perfect transparency to the case company's purchase department.

Performance of high power fibre laser cutting of thick-section steel and mediumsection aluminium

Cutting of thick section stainless steel and mild steel, and medium section aluminium using the high power ytterbium fibre laser has been experimentally investigated in this study. Theoretical models of the laser power requirement for cutting of a metal workpiece and the melt removal rate were also developed. The calculated laser power requirement was correlated to the laser power used for the cutting of 10 mm stainless steel workpiece and 15 mm mild steel workpiece using the ytterbium fibre laser and the CO2 laser. Nitrogen assist gas was used for cutting of stainless steel and oxygen was used for mild steel cutting. It was found that the incident laser power required for cutting at a given cutting speed was lower for fibre laser cutting than for CO2 laser cutting indicating a higher absorptivity of the fibre laser beam by the workpiece and higher melting efficiency for the fibre laser beam than for the CO2 laser beam. The difficulty in achieving an efficient melt removal during high speed cutting of the 15 mmmild steel workpiece with oxygen assist gas using the ytterbium fibre laser can be attributed to the high melting efficiency of the ytterbium fibre laser. The calculated melt flow velocity and melt film thickness correlated well with the location of the boundary layer separation point on the 10 mm stainless steel cut edges. An increase in the melt film thickness caused by deceleration of the melt particles in the boundary layer by the viscous shear forces results in the flow separation. The melt flow velocity increases with an increase in assist gas pressure and cut kerf width resulting in a reduction in the melt film thickness and the boundary layer separation point moves closer to the bottom cut edge. The cut edge quality was examined by visual inspection of the cut samples and measurement of the cut kerf width, boundary layer separation point, cut edge squareness (perpendicularity) deviation, and cut edge surface roughness as output quality factors. Different regions of cut edge quality in 10 mm stainless steel and 4 mm aluminium workpieces were defined for different combinations of cutting speed and laserpower.Optimization of processing parameters for a high cut edge quality in 10 mmstainless steel was demonstrated

Network effects: Scale development and implications for new product performance

More and more innovations currently being commercialized exhibit network effects, in other words, the value of using the product increases as more and more people use the same or compatible products. Although this phenomenon has been the subject of much theoretical debate in economics, marketing researchers have been slow to respond to the growing importance of network effects in new product success. Despite an increase in interest in recent years, there is no comprehensive view on the phenomenon and, therefore, there is currently incomplete understanding of the dimensions it incorporates. Furthermore, there is wide dispersion in operationalization, in other words, the measurement of network effects, and currently available approaches have various shortcomings that limit their applicability, especially in marketing research. Consequently, little is known today about how these products fare on the marketplace and how they should be introduced in order to maximize their chances of success. Hence, the motivation for this study was driven by the need to increase our knowledge and understanding of the nature of network effects as a phenomenon, and of their role in the commercial success of new products. This thesis consists of two parts. The first part comprises a theoretical overview of the relevant literature, and presents the conclusions of the entire study. The second part comprises five complementary, empirical research publications. Quantitative research methods and two sets of quantitative data are utilized. The results of the study suggest that there is a need to update both the conceptualization and the operationalization of the phenomenon of network effects. Furthermore, there is a need for an augmented view on customers’ perceived value in the context of network effects, given that the nature of value composition has major implications for the viability of such products in the marketplace. The role of network effects in new product performance is not as straightforward as suggested in the existing theoretical literature. The overwhelming result of this study is that network effects do not directly influence product success, but rather enhance or suppress the influence of product introduction strategies. The major contribution of this study is in conceptualizing the phenomenon of network effects more comprehensively than has been attempted thus far. The study gives an augmented view of the nature of customer value in network markets, which helps in explaining why some products thrive on these markets whereas others never catch on. Second, the study discusses shortcomings in prior literature in the way it has operationalized network effects, suggesting that these limitations can be overcome in the research design. Third, the study provides some much-needed empirical evidence on how network effects, product introduction strategies, and new product performance are associated. In general terms, this thesis adds to our knowledge of how firms can successfully leverage network effects in product commercialization in order to improve market performance.

Role of Capabilities in Purchasing and Supply Management Performance

The objective of this thesis was to study the role of capabilities in purchasing and supply management. For the pre-understanding of the research topic, purchasing and supply management development and the multidimensional, unstructured and complex nature of purchasing and supply management performance was studied in literature review. In addition, a capability-based purchasing and supply management performance framework were researched and structured for the empirical research. Due to the unstructured nature of the research topic, the empirical research is three-pronged in this study including three different research methods: the Delphi method, semi-structured interview, and case research. As a result, the purchasing and supply management capability assessment tool was structured to measure current level of capabilities and impact of capabilities on purchasing and supply management performance. The final results indicate that capabilities are enablers of purchasing and supply management performance, and therefore critical to purchasing and supply performance.