Expression of the inducible NO synthase in human monocytic U937 cells allows high output nitric oxide production.

Nitric oxide (NO) produced by inducible NO synthase (iNOS, NOS-2) is an important component of the macrophage-mediated immune defense toward numerous pathogens. Murine macrophages produce NO after cytokine activation, whereas, under similar conditions, human macrophages produce low levels or no NO at all. Although human macrophages can express iNOS mRNA and protein on activation, whether they possess the complete machinery necessary for NO synthesis remains controversial. To define the conditions necessary for human monocytes/macrophages to synthesize NO when expressing a functional iNOS, the human monocytic U937 cell line was engineered to synthesize this enzyme, following infection with a retroviral expression vector containing human hepatic iNOS (DFGiNOS). Northern blot and Western blot analysis confirmed the expression of iNOS in transfected U937 cells both at the RNA and protein levels. NOS enzymatic activity was demonstrated in cell lysates by the conversion of L-[3H]arginine into L-[3H]citrulline and the production of NO by intact cells was measured by nitrite and nitrate accumulation in culture supernatants. When expressing functional iNOS, U937 cells were capable of releasing high levels of NO. NO production was strictly dependent on supplementation of the culture medium with tetrahydrobiopterin (BH4) and was not modified by stimulation of the cells with different cytokines. These observations suggest that (1) human monocytic U937 cells contain all the cofactors necessary for NO synthesis, except BH4 and (2) the failure to detect NO in cytokine-stimulated untransfected U937 cells is not due to the presence of a NO-scavenging molecule within these cells nor to the destabilization of iNOS protein. DFGiNOS U937 cells represent a valuable human model to study the role of NO in immunity toward tumors and pathogens.

Lifetime enhancement of scroll rings by spatiotemporal fluctuations

The dynamics of three-dimensional scroll rings with spatiotemporal random excitability is investigated numerically using the FitzHugh-Nagumo model. Depending on the correlation time and length scales of the fluctuations, the lifetime of the ring filament is enlarged and a resonance effect between the time scale of the scroll ring and the time correlation of the noise is observed. Numerical results are interpreted in terms of a simplified stochastic model derived from the kinematical equations for three-dimensional excitable waves.

Lifetime enhancement of scroll rings by spatiotemporal fluctuations

The dynamics of three-dimensional scroll rings with spatiotemporal random excitability is investigated numerically using the FitzHugh-Nagumo model. Depending on the correlation time and length scales of the fluctuations, the lifetime of the ring filament is enlarged and a resonance effect between the time scale of the scroll ring and the time correlation of the noise is observed. Numerical results are interpreted in terms of a simplified stochastic model derived from the kinematical equations for three-dimensional excitable waves.

Identifying strategies for mitigating the global warming impact of the EU-25 economy using a multi-objective input-output approach

Global warming mitigation has recently become a priority worldwide. A large body of literature dealing with energy related problems has focused on reducing greenhouse gases emissions at an engineering scale. In contrast, the minimization of climate change at a wider macroeconomic level has so far received much less attention. We investigate here the issue of how to mitigate global warming by performing changes in an economy. To this end, we make use of a systematic tool that combines three methods: linear programming, environmentally extended input output models, and life cycle assessment principles. The problem of identifying key economic sectors that contribute significantly to global warming is posed in mathematical terms as a bi criteria linear program that seeks to optimize simultaneously the total economic output and the total life cycle CO2 emissions. We have applied this approach to the European Union economy, finding that significant reductions in global warming potential can be attained by regulating specific economic sectors. Our tool is intended to aid policymakers in the design of more effective public policies for achieving the environmental and economic targets sought.

Towards input/output-free modelling of linear infinite-dimensional systems in continuous time

This dissertation describes a networking approach to infinite-dimensional systems theory, where there is a minimal distinction between inputs and outputs. We introduce and study two closely related classes of systems, namely the state/signal systems and the port-Hamiltonian systems, and describe how they relate to each other. Some basic theory for these two classes of systems and the interconnections of such systems is provided. The main emphasis lies on passive and conservative systems, and the theoretical concepts are illustrated using the example of a lossless transfer line. Much remains to be done in this field and we point to some directions for future studies as well.

Solving Leontief Input-Output Model with Trapezoidal Fuzzy Numbers and Gauss-Seidel Algorithm

In this work a fuzzy linear system is used to solve Leontief input-output model with fuzzy entries. For solving this model, we assume that the consumption matrix from di erent sectors of the economy and demand are known. These assumptions heavily depend on the information obtained from the industries. Hence uncertainties are involved in this information. The aim of this work is to model these uncertainties and to address them by fuzzy entries such as fuzzy numbers and LR-type fuzzy numbers (triangular and trapezoidal). Fuzzy linear system has been developed using fuzzy data and it is solved using Gauss-Seidel algorithm. Numerical examples show the e ciency of this algorithm. The famous example from Prof. Leontief, where he solved the production levels for U.S. economy in 1958, is also further analyzed.

Stochastic variability of output levels in a pulp mill

Quite often, in the construction of a pulp mill involves establishing the size of tanks which will accommodate the material from the various processes in which case estimating the right tank size a priori would be vital. Hence, simulation of the whole production process would be worthwhile. Therefore, there is need to develop mathematical models that would mimic the behavior of the output from the various production units of the pulp mill to work as simulators. Markov chain models, Autoregressive moving average (ARMA) model, Mean reversion models with ensemble interaction together with Markov regime switching models are proposed for that purpose.

Active inverter output filtering methods

Frequency converters are widely used in the industry to enable better controllability and efficiency of variable speed AC motor drives. Despite these advantages, certain challenges concerning the inverter and motor interfacing have been present for decades. As insulated gate bipolar transistors entered the market, the inverter output voltage transition rate significantly increased compared with their predecessors. Inverters operate based on pulse width modulation of the output voltage, and the steep voltage edge fed by the inverter produces a motor terminal overvoltage. The overvoltage causes extra stress to the motor insulation, which may lead to a prematuremotor failure. The overvoltage is not generated by the inverter alone, but also by the sum effect of the motor cable length and the impedance mismatch between the cable and the motor. Many solutions have been shown to limit the overvoltage, and the mainstream products focus on passive filters. This doctoral thesis studies an alternative methodology for motor overvoltage reduction. The focus is on minimization of the passive filter dimensions, physical and electrical, or better yet, on operation without any filter. This is achieved by additional inverter control and modulation. The studied methods are implemented on different inverter topologies, varying in nominal voltage and current.For two-level inverters, the studied method is termed active du/dt. It consists of a small output LC filter, which is controlled by an independent modulator. The overvoltage is limited by a reduced voltage transition rate. For multilevel inverters, an overvoltage mitigation method operating without a passive filter, called edge modulation, is implemented. The method uses the capability of the inverter to produce two switching operations in the same direction to cancel the oscillating voltages of opposite phases. For parallel inverters, two methods are studied. They are both intended for two-level inverters, but the first uses individual motor cables from each inverter while the other topology applies output inductors. The overvoltage is reduced by interleaving the switching operations to produce a similar oscillation accumulation as with the edge modulation. The implementation of these methods is discussed in detail, and the necessary modifications to the control system of the inverter are presented. Each method is experimentally verified by operating industrial frequency converters with the modified control. All the methods are found feasible, and they provide sufficient overvoltage protection. The limitations and challenges brought about by the methods are discussed.

Practical Framework for Monitoring the Performance of Agile IT Projects in an Output-Based Outsourcing Context

Over the past decade, organizations worldwide have begun to widely adopt agile software development practices, which offer greater flexibility to frequently changing business requirements, better cost effectiveness due to minimization of waste, faster time-to-market, and closer collaboration between business and IT. At the same time, IT services are continuing to be increasingly outsourced to third parties providing the organizations with the ability to focus on their core capabilities as well as to take advantage of better demand scalability, access to specialized skills, and cost benefits. An output-based pricing model, where the customers pay directly for the functionality that was delivered rather than the effort spent, is quickly becoming a new trend in IT outsourcing allowing to transfer the risk away from the customer while at the same time offering much better incentives for the supplier to optimize processes and improve efficiency, and consequently producing a true win-win outcome. Despite the widespread adoption of both agile practices and output-based outsourcing, there is little formal research available on how the two can be effectively combined in practice. Moreover, little practical guidance exists on how companies can measure the performance of their agile projects, which are being delivered in an output-based outsourced environment. This research attempted to shed light on this issue by developing a practical project monitoring framework which may be readily applied by organizations to monitor the performance of agile projects in an output-based outsourcing context, thus taking advantage of the combined benefits of such an arrangement Modified from action research approach, this research was divided into two cycles, each consisting of the Identification, Analysis, Verification, and Conclusion phases. During Cycle 1, a list of six Key Performance Indicators (KPIs) was proposed and accepted by the professionals in the studied multinational organization, which formed the core of the proposed framework and answered the first research sub-question of what needs to be measured. In Cycle 2, a more in-depth analysis was provided for each of the suggested Key Performance Indicators including the techniques for capturing, calculating, and evaluating the information provided by each KPI. In the course of Cycle 2, the second research sub-question was answered, clarifying how the data for each KPI needed to be measured, interpreted, and acted upon. Consequently, after two incremental research cycles, the primary research question was answered describing the practical framework that may be used for monitoring the performance of agile IT projects delivered in an output-based outsourcing context. This framework was evaluated by the professionals within the context of the studied organization and received positive feedback across all four evaluation criteria set forth in this research, including the low overhead of data collection, high value of provided information, ease of understandability of the metric dashboard, and high generalizability of the proposed framework.

Power semiconductor nonlinearities in active du/dt output filtering

This doctoral thesis introduces an improved control principle for active du/dt output filtering in variable-speed AC drives, together with performance comparisons with previous filtering methods. The effects of power semiconductor nonlinearities on the output filtering performance are investigated. The nonlinearities include the timing deviation and the voltage pulse waveform distortion in the variable-speed AC drive output bridge. Active du/dt output filtering (ADUDT) is a method to mitigate motor overvoltages in variable-speed AC drives with long motor cables. It is a quite recent addition to the du/dt reduction methods available. This thesis improves on the existing control method for the filter, and concentrates on the lowvoltage (below 1 kV AC) two-level voltage-source inverter implementation of the method. The ADUDT uses narrow voltage pulses having a duration in the order of a microsecond from an IGBT (insulated gate bipolar transistor) inverter to control the output voltage of a tuned LC filter circuit. The filter output voltage has thus increased slope transition times at the rising and falling edges, with an opportunity of no overshoot. The effect of the longer slope transition times is a reduction in the du/dt of the voltage fed to the motor cable. Lower du/dt values result in a reduction in the overvoltage effects on the motor terminals. Compared with traditional output filtering methods to accomplish this task, the active du/dt filtering provides lower inductance values and a smaller physical size of the filter itself. The filter circuit weight can also be reduced. However, the power semiconductor nonlinearities skew the filter control pulse pattern, resulting in control deviation. This deviation introduces unwanted overshoot and resonance in the filter. The controlmethod proposed in this thesis is able to directly compensate for the dead time-induced zero-current clamping (ZCC) effect in the pulse pattern. It gives more flexibility to the pattern structure, which could help in the timing deviation compensation design. Previous studies have shown that when a motor load current flows in the filter circuit and the inverter, the phase leg blanking times distort the voltage pulse sequence fed to the filter input. These blanking times are caused by excessively large dead time values between the IGBT control pulses. Moreover, the various switching timing distortions, present in realworld electronics when operating with a microsecond timescale, bring additional skew to the control. Left uncompensated, this results in distortion of the filter input voltage and a filter self-induced overvoltage in the form of an overshoot. This overshoot adds to the voltage appearing at the motor terminals, thus increasing the transient voltage amplitude at the motor. This doctoral thesis investigates the magnitude of such timing deviation effects. If the motor load current is left uncompensated in the control, the filter output voltage can overshoot up to double the input voltage amplitude. IGBT nonlinearities were observed to cause a smaller overshoot, in the order of 30%. This thesis introduces an improved ADUDT control method that is able to compensate for phase leg blanking times, giving flexibility to the pulse pattern structure and dead times. The control method is still sensitive to timing deviations, and their effect is investigated. A simple approach of using a fixed delay compensation value was tried in the test setup measurements. The ADUDT method with the new control algorithm was found to work in an actual motor drive application. Judging by the simulation results, with the delay compensation, the method should ultimately enable an output voltage performance and a du/dt reduction that are free from residual overshoot effects. The proposed control algorithm is not strictly required for successful ADUDT operation: It is possible to precalculate the pulse patterns by iteration and then for instance store them into a look-up table inside the control electronics. Rather, the newly developed control method is a mathematical tool for solving the ADUDT control pulses. It does not contain the timing deviation compensation (from the logic-level command to the phase leg output voltage), and as such is not able to remove the timing deviation effects that cause error and overshoot in the filter. When the timing deviation compensation has to be tuned-in in the control pattern, the precalculated iteration method could prove simpler and equally good (or even better) compared with the mathematical solution with a separate timing compensation module. One of the key findings in this thesis is the conclusion that the correctness of the pulse pattern structure, in the sense of ZCC and predicted pulse timings, cannot be separated from the timing deviations. The usefulness of the correctly calculated pattern is reduced by the voltage edge timing errors. The doctoral thesis provides an introductory background chapter on variable-speed AC drives and the problem of motor overvoltages and takes a look at traditional solutions for overvoltage mitigation. Previous results related to the active du/dt filtering are discussed. The basic operation principle and design of the filter have been studied previously. The effect of load current in the filter and the basic idea of compensation have been presented in the past. However, there was no direct way of including the dead time in the control (except for solving the pulse pattern manually by iteration), and the magnitude of nonlinearity effects had not been investigated. The enhanced control principle with the dead time handling capability and a case study of the test setup timing deviations are the main contributions of this doctoral thesis. The simulation and experimental setup results show that the proposed control method can be used in an actual drive. Loss measurements and a comparison of active du/dt output filtering with traditional output filtering methods are also presented in the work. Two different ADUDT filter designs are included, with ferrite core and air core inductors. Other filters included in the tests were a passive du/dtfilter and a passive sine filter. The loss measurements incorporated a silicon carbide diode-equipped IGBT module, and the results show lower losses with these new device technologies. The new control principle was measured in a 43 A load current motor drive system and was able to bring the filter output peak voltage from 980 V (the previous control principle) down to 680 V in a 540 V average DC link voltage variable-speed drive. A 200 m motor cable was used, and the filter losses for the active du/dt methods were 111W–126 W versus 184 W for the passive du/dt. In terms of inverter and filter losses, the active du/dt filtering method had a 1.82-fold increase in losses compared with an all-passive traditional du/dt output filter. The filter mass with the active du/dt method was 17% (2.4 kg, air-core inductors) compared with 14 kg of the passive du/dt method filter. Silicon carbide freewheeling diodes were found to reduce the inverter losses in the active du/dt filtering by 18% compared with the same IGBT module with silicon diodes. For a 200 m cable length, the average peak voltage at the motor terminals was 1050 V with no filter, 960 V for the all-passive du/dt filter, and 700 V for the active du/dt filtering applying the new control principle.

An optically coupled power stimulus isolation unit with high voltage and fast rise time output

Recent technological developments have created new devices that could improve and simplify the construction of stimulus isolators. HEXFET transistors can switch large currents and hundreds of volts in nanoseconds. The newer opto-isolators can give a pulse rise time of a few nanoseconds, with output compatible with MOSFET devices, in which delays are reduced to nanoseconds. Integrated DC/DC converters are now available. Using these new resources we developed a new electrical stimulus isolator circuit with selectable constant-current and constant-voltage modes, which are precise and easy to construct. The circuit works like a regulated power supply in both modes with output switched to zero or to free mode through an opto-isolator device. The isolator analyses showed good practical performance. The output to ground resistance was 1011 ohms and capacitance 35 picofarads. The rise time and fall time were identical (5 µs) and constant. The selectable voltage or current output mode made it very convenient to use. The current mode, with higher output resistance values in low current ranges, permits intracellular stimulation even with tip resistances close to 100 megaohms. The high compliance of 200 V guarantees the value of the current stimulus. The very low output resistance in the voltage mode made the device highly suitable for extracellular stimulation with low impedance electrodes. Most importantly, these characteristics were achieved with a circuit that was easy to build and modify and assembled with components available in Brazil.

Behavioral correlates of the activity of serotonergic and non-serotonergic neurons in caudal raphe nuclei

We investigated the behavioral correlates of the activity of serotonergic and non-serotonergic neurons in the nucleus raphe pallidus (NRP) and nucleus raphe obscurus (NRO) of unanesthetized and unrestrained cats. The animals were implanted with electrodes for recording single unit activity, parietal oscillographic activity, and splenius, digastric and masseter electromyographic activities. They were tested along the waking-sleep cycle, during sensory stimulation and during drinking behavior. The discharge of the serotonergic neurons decreased progressively from quiet waking to slow wave sleep and to fast wave sleep. Ten different patterns of relative discharge across the three states were observed for the non-serotonergic neurons. Several non-serotonergic neurons showed cyclic discharge fluctuations related to respiration during one, two or all three states. While serotonergic neurons were usually unresponsive to the sensory stimuli used, many non-serotonergic neurons responded to these stimuli. Several non-serotonergic neurons showed a phasic relationship with splenius muscle activity during auditory stimulation. One serotonergic neuron showed a tonic relationship with digastric muscle activity during drinking behavior. A few non-serotonergic neurons exhibited a tonic relationship with digastric and/or masseter muscle activity during this behavior. Many non-serotonergic neurons exhibited a phasic relationship with these muscle activities, also during this behavior. These results suggest that the serotonergic neurons in the NRP and NRO constitute a relatively homogeneous population from a functional point of view, while the non-serotonergic neurons form groups with considerable functional specificity. The data support the idea that the NRP and NRO are implicated in the control of somatic motor output.

Energy and raw material consumption analysis of powder bed fusion: case study: CNC machining and laser additive manufacturing

Laser additive manufacturing (LAM), known also as 3D printing, is a powder bed fusion (PBF) type of additive manufacturing (AM) technology used to manufacture metal parts layer by layer by assist of laser beam. The development of the technology from building just prototype parts to functional parts is due to design flexibility. And also possibility to manufacture tailored and optimised components in terms of performance and strength to weight ratio of final parts. The study of energy and raw material consumption in LAM is essential as it might facilitate the adoption and usage of the technique in manufacturing industries. The objective this thesis was find the impact of LAM on environmental and economic aspects and to conduct life cycle inventory of CNC machining and LAM in terms of energy and raw material consumption at production phases. Literature overview in this thesis include sustainability issues in manufacturing industries with focus on environmental and economic aspects. Also life cycle assessment and its applicability in manufacturing industry were studied. UPLCI-CO2PE! Initiative was identified as mostly applied exiting methodology to conduct LCI analysis in discrete manufacturing process like LAM. Many of the reviewed literature had focused to PBF of polymeric material and only few had considered metallic materials. The studies that had included metallic materials had only measured input and output energy or materials of the process and compared to different AM systems without comparing to any competitive process. Neither did any include effect of process variation when building metallic parts with LAM. Experimental testing were carried out to make dissimilar samples with CNC machining and LAM in this thesis. Test samples were designed to include part complexity and weight reductions. PUMA 2500Y lathe machine was used in the CNC machining whereas a modified research machine representing EOSINT M-series was used for the LAM. The raw material used for making the test pieces were stainless steel 316L bar (CNC machined parts) and stainless steel 316L powder (LAM built parts). An analysis of power, time, and the energy consumed in each of the manufacturing processes on production phase showed that LAM utilises more energy than CNC machining. The high energy consumption was as result of duration of production. Energy consumption profiles in CNC machining showed fluctuations with high and low power ranges. LAM energy usage within specific mode (standby, heating, process, sawing) remained relatively constant through the production. CNC machining was limited in terms of manufacturing freedom as it was not possible to manufacture all the designed sample by machining. And the one which was possible was aided with large amount of material removed as waste. Planning phase in LAM was shorter than in CNC machining as the latter required many preparation steps. Specific energy consumption (SEC) were estimated in LAM based on the practical results and assumed platform utilisation. The estimated platform utilisation showed SEC could reduce when more parts were placed in one build than it was in with the empirical results in this thesis (six parts).

The decreased oxygen uptake during progressive exercise in ischemia-induced heart failure is due to reduced cardiac output rate

We tested the hypothesis that the inability to increase cardiac output during exercise would explain the decreased rate of oxygen uptake (VO2) in recent onset, ischemia-induced heart failure rats. Nine normal control rats and 6 rats with ischemic heart failure were studied. Myocardial infarction was induced by coronary ligation. VO2 was measured during a ramp protocol test on a treadmill using a metabolic mask. Cardiac output was measured with a flow probe placed around the ascending aorta. Left ventricular end-diastolic pressure was higher in ischemic heart failure rats compared with normal control rats (17 ± 0.4 vs 8 ± 0.8 mmHg, P = 0.0001). Resting cardiac index (CI) tended to be lower in ischemic heart failure rats (P = 0.07). Resting heart rate (HR) and stroke volume index (SVI) did not differ significantly between ischemic heart failure rats and normal control rats. Peak VO2 was lower in ischemic heart failure rats (73.72 ± 7.37 vs 109.02 ± 27.87 mL min-1 kg-1, P = 0.005). The VO2 and CI responses during exercise were significantly lower in ischemic heart failure rats than in normal control rats. The temporal response of SVI, but not of HR, was significantly lower in ischemic heart failure rats than in normal control rats. Peak CI, HR, and SVI were lower in ischemic heart failure rats. The reduction in VO2 response during incremental exercise in an ischemic model of heart failure is due to the decreased cardiac output response, largely caused by depressed stroke volume kinetics.