Identification of in vitro HSC fate regulators by differential lipid raft clustering.

Most hematopoietic stem cells (HSC) in the bone marrow reside in a quiescent state and occasionally enter the cell cycle upon cytokine-induced activation. Although the mechanisms regulating HSC quiescence and activation remain poorly defined, recent studies have revealed a role of lipid raft clustering (LRC) in HSC activation. Here, we tested the hypothesis that changes in lipid raft distribution could serve as an indicator of the quiescent and activated state of HSCs in response to putative niche signals. A semi-automated image analysis tool was developed to map the presence or absence of lipid raft clusters in live HSCs cultured for just one hour in serum-free medium supplemented with stem cell factor (SCF). By screening the ability of 19 protein candidates to alter lipid raft dynamics, we identified six factors that induced either a marked decrease (Wnt5a, Wnt3a and Osteopontin) or increase (IL3, IL6 and VEGF) in LRC. Cell cycle kinetics of single HSCs exposed to these factors revealed a correlation of LRC dynamics and proliferation kinetics: factors that decreased LRC slowed down cell cycle kinetics, while factors that increased LRC led to faster and more synchronous cycling. The possibility of identifying, by LRC analysis at very early time points, whether a stem cell is activated and possibly committed upon exposure to a signaling cue of interest could open up new avenues for large-scale screening efforts.

Pinnan ominaisuuksien karakterisointi kiiltomittalaitteella ja kiiltomittalaitteen soveltuvuus tuotannon laadunvarmistuksessa

Alahuulten, kärkilistojen, turboputkien ja telapinnoitteiden pinnankarheutta mitataan Rautpohjan tehtaalla nykyään pääosin koskettavalla pinnankarheusprofilometrilla. Profilometrin käyttö on hankalaa ja epäluotettavaa tai käytössä on muita ongelmia. Paperin kuituorientaation mittaamiseen käytetään nykyisin mm. TSO-menetelmää tai repäisymenetelmää. Tämän diplomityön tarkoituksena oli kartoittaa diffraktiiviseen optiseen elementtiin perustuvan kiiltomittalaiteprototyypin mahdollisuuksia karakteroida pinnan ominaisuuksia ja tutkia kiiltomittalaitteen soveltuvuutta tuotannon laadunvarmistuksessa. Alahuuli-, kärkilista-, turboputki-, telapinnoite- ja paperinäytteistä valmistettiinnäytesarjoja, jotka mitattiin nykymenetelmin ja kiiltomittalaitteella. Tulostenkorreloituvuutta tutkittiin ja taloudellista merkitystä arvioitiin investointilaskelmin. Paperin kuituorientaation, paperin pinnan kuituorientaation ja telapinnoitteiden mittaaminen kiiltomittalaitteella osoittautui taloudellisesti erittäin merkittäväksi. Ennen mahdollista kiiltomittalaitteen käyttöönottoa prototyyppiä on kehitettävä, kiillon korreloituvuutta tulee tutkia edelleen ja aiheesta on tehtävä lisätutkimuksia.

Pienvesivoimalanmallinnus ja jakeluverkkovaikutusten tarkastelu

Tässä työssä simuloitiin Valkealassa sijaitsevaa Tirvan pienvesivoimalaitosta ja sen vaikutusta sähkönjakeluverkkoon. Pienvesivoimalaitos mallinnettiin PSCAD-ympäristöön verkko- ja voimalaitostietojen perusteella. Sähköverkko kuvattiin malliin koko 110 kV:n siirtävän verkon ja Tirvan pienjänniteverkon väliltä. Mallin avulla tehtiin sarja hajautettua sähköntuotantoa koskevia tarkasteluita. Tarkasteluissa huomattiin voimalaitoksen verkkoonliitynnän aiheuttavan standardien ylärajoilla olevan transienttisen muutoksen voimalaitoksen jännitteisiin. Työssä tehtiin yksityiskohtaisempi jännitehäviöiden mittaus voimalaitoksen pullonkaulana toimivalle pienitehoiselle jakelumuuntajalle. Tuotannon lisäämisen yhteydessä näkyvän yllättävän jännitteen laskun syyt paikannettiin muuntajalla tapahtuviin loistehon siirrosta johtuviin ylimääräisiin jännitehäviöihin. Voimalaitoksella ei ole merkittävää vaikutusta vikatilanteiden virtoihin.

Kestomagneettitahtikoneen lämpömallinnus

Sähkökoneenterminen suunnittelu on yhtä tärkeätä kuin koneen sähköisten piirien ja magneettipiirin mitoitus, koska koneen lämpenemä määrää koneesta saatavan tehon. Pääosasähkökoneista suunnitellaan edelleen ns. perimätiedon avulla, jossa tukeudutaanvalmiiksi koeteltuihin ratkaisuihin ja kokemusperäiseen tietoon tiettyjen rakenteiden toimivuudesta. Perinteisin menetelmin uusia konerakenteita suunniteltaessa ei pystytä saamaan luotettavaa tietoa uusien ratkaisuiden toimivuudesta. Etenkin hitaasti pyörivien ja suuren vääntötiheyden omaavien kestomagneettitahtikoneiden jäähdytyksen mitoitus on ongelmallista. Siten tarve kehittää analyyttisiä työkaluja lämpenemän mallinnukseen on perusteltua. Tässä työssäperehdytään suuren tehotiheyden omaavien kestomagneettikoneiden urakoon ja virrantiheyden valintaan termisen mitoituksen kannalta. Työn tavoitteena on laatia yksinkertainen analyyttinen työkalu urakoon ja virrantiheyden valintaan. Työkaluavoidaan hyödyntää jo koneensuunnittelun alkuvaiheessa.

Cenomanian-Turonian transition in a shallow water sequence of the Sinai, Egypt

Environmental and depositional changes across the Late Cenomanian oceanic anoxic event (OAE2) in the Sinai, Egypt, are examined based on biostratigraphy, mineralogy, delta(13)C values and phosphorus analyses. Comparison with the Pueblo, Colorado, stratotype section reveals the Whadi El Ghaib section as stratigraphically complete across the late Cenomanian-early Turonian. Foraminifera are dominated by high-stress planktic and benthic assemblages characterized by low diversity, low-oxygen and low-salinity tolerant species, which mark shallow-water oceanic dysoxic conditions during OAE2. Oyster biostromes suggest deposition occurred in less than 50 m depths in low-oxygen, brackish, and nutrient-rich waters. Their demise prior to the peak delta(13)C excursion is likely due to a rising sea-level. Characteristic OAE2 anoxic conditions reached this coastal region only at the end of the delta(13)C plateau in deeper waters near the end of the Cenomanian. Increased phosphorus accumulations before and after the delta(13)C excursion suggest higher oxic conditions and increased detrital input. Bulk-rock and clay mineralogy indicate humid climate conditions, increased continental runoff and a rising sea up to the first delta(13)C peak. Above this interval, a dryer and seasonally well-contrasted climate with intermittently dry conditions prevailed. These results reveal the globally synchronous delta(13)C shift, but delayed effects of OAE2 dependent on water depth.

The role of auditory cortices in the retrieval of single-trial auditory-visual object memories.

Single-trial encounters with multisensory stimuli affect both memory performance and early-latency brain responses to visual stimuli. Whether and how auditory cortices support memory processes based on single-trial multisensory learning is unknown and may differ qualitatively and quantitatively from comparable processes within visual cortices due to purported differences in memory capacities across the senses. We recorded event-related potentials (ERPs) as healthy adults (n = 18) performed a continuous recognition task in the auditory modality, discriminating initial (new) from repeated (old) sounds of environmental objects. Initial presentations were either unisensory or multisensory; the latter entailed synchronous presentation of a semantically congruent or a meaningless image. Repeated presentations were exclusively auditory, thus differing only according to the context in which the sound was initially encountered. Discrimination abilities (indexed by d') were increased for repeated sounds that were initially encountered with a semantically congruent image versus sounds initially encountered with either a meaningless or no image. Analyses of ERPs within an electrical neuroimaging framework revealed that early stages of auditory processing of repeated sounds were affected by prior single-trial multisensory contexts. These effects followed from significantly reduced activity within a distributed network, including the right superior temporal cortex, suggesting an inverse relationship between brain activity and behavioural outcome on this task. The present findings demonstrate how auditory cortices contribute to long-term effects of multisensory experiences on auditory object discrimination. We propose a new framework for the efficacy of multisensory processes to impact both current multisensory stimulus processing and unisensory discrimination abilities later in time.

On solving fair exchange and related distributed problems in Byzantine environments

Abstract The solvability of the problem of fair exchange in a synchronous system subject to Byzantine failures is investigated in this work. The fair exchange problem arises when a group of processes are required to exchange digital items in a fair manner, which means that either each process obtains the item it was expecting or no process obtains any information on, the inputs of others. After introducing a novel specification of fair exchange that clearly separates safety and liveness, we give an overview of the difficulty of solving such a problem in the context of a fully-connected topology. On one hand, we show that no solution to fair exchange exists in the absence of an identified process that every process can trust a priori; on the other, a well-known solution to fair exchange relying on a trusted third party is recalled. These two results lead us to complete our system model with a flexible representation of the notion of trust. We then show that fair exchange is solvable if and only if a connectivity condition, named the reachable majority condition, is satisfied. The necessity of the condition is proven by an impossibility result and its sufficiency by presenting a general solution to fair exchange relying on a set of trusted processes. The focus is then turned towards a specific network topology in order to provide a fully decentralized, yet realistic, solution to fair exchange. The general solution mentioned above is optimized by reducing the computational load assumed by trusted processes as far as possible. Accordingly, our fair exchange protocol relies on trusted tamperproof modules that have limited communication abilities and are only required in key steps of the algorithm. This modular solution is then implemented in the context of a pedagogical application developed for illustrating and apprehending the complexity of fair exchange. This application, which also includes the implementation of a wide range of Byzantine behaviors, allows executions of the algorithm to be set up and monitored through a graphical display. Surprisingly, some of our results on fair exchange seem contradictory with those found in the literature of secure multiparty computation, a problem from the field of modern cryptography, although the two problems have much in common. Both problems are closely related to the notion of trusted third party, but their approaches and descriptions differ greatly. By introducing a common specification framework, a comparison is proposed in order to clarify their differences and the possible origins of the confusion between them. This leads us to introduce the problem of generalized fair computation, a generalization of fair exchange. Finally, a solution to this new problem is given by generalizing our modular solution to fair exchange

Validation Studies of Thermal-hydraulic Code for Safety Analysis of Nuclear Power Plants

This thesis gives an overview of the validation process for thermal hydraulic system codes and it presents in more detail the assessment and validation of the French code CATHARE for VVER calculations. Three assessment cases are presented: loop seal clearing, core reflooding and flow in a horizontal steam generator. The experience gained during these assessment and validation calculations has been used to analyze the behavior of the horizontal steam generator and the natural circulation in the geometry of the Loviisa nuclear power plant. The cases presented are not exhaustive, but they give a good overview of the work performed by the personnel of Lappeenranta University of Technology (LUT). Large part of the work has been performed in co-operation with the CATHARE-team in Grenoble, France. The design of a Russian type pressurized water reactor, VVER, differs from that of a Western-type PWR. Most of thermal-hydraulic system codes are validated only for the Western-type PWRs. Thus, the codes should be assessed and validated also for VVER design in order to establish any weaknesses in the models. This information is needed before codes can be used for the safety analysis. Theresults of the assessment and validation calculations presented here show that the CATHARE code can be used also for the thermal-hydraulic safety studies for VVER type plants. However, some areas have been indicated which need to be reassessed after further experimental data become available. These areas are mostly connected to the horizontal stem generators, like condensation and phase separation in primary side tubes. The work presented in this thesis covers a large numberof the phenomena included in the CSNI code validation matrices for small and intermediate leaks and for transients. Also some of the phenomena included in the matrix for large break LOCAs are covered. The matrices for code validation for VVER applications should be used when future experimental programs are planned for code validation.

Effect of Noncondensable Gases on Circulation of Primary Coolant in Nuclear Power Plants in Abnormal Situations

The present study focuses on two effects of the presence of a noncondensable gas on the thermal-hydraulic behavior of thecoolant of the primary circuit of a nuclear reactor in the VVER-440 geometry inabnormal situations. First, steam condensation with the presence of air was studied in the horizontal tubes of the steam generator (SG) of the PACTEL test facility. The French thermal-hydraulic CATHARE code was used to study the heat transfer between the primary and secondary side in conditions derived from preliminary experiments performed by VTT using PACTEL. In natural circulation and single-phase vapor conditions, the injection of a volume of air, equivalent to the totalvolume of the primary side of the SG at the entrance of the hot collector, did not stop the heat transfer from the primary to the secondary side. The calculated results indicate that air is located in the second half-length (from the mid-length of the tubes to the cold collector) in all the tubes of the steam generator The hot collector remained full of steam during the transient. Secondly, the potential release of the nitrogen gas dissolved in the water of the accumulators of the emergency core coolant system of the Loviisa nuclear power plant (NPP) was investigated. The author implemented a model of the dissolution and release ofnitrogen gas in the CATHARE code; the model created by the CATHARE developers. In collaboration with VTT, an analytical experiment was performed with some components of PACTEL to determine, in particular, the value of the release time constant of the nitrogen gas in the depressurization conditions representative of the small and intermediate break transients postulated for the Loviisa NPP. Such transients, with simplified operating procedures, were calculated using the modified CATHARE code for various values of the release time constant used in the dissolution and release model. For the small breaks, nitrogen gas is trapped in thecollectors of the SGs in rather large proportions. There, the levels oscillate until the actuation of the low-pressure injection pumps (LPIS) that refill the primary circuit. In the case of the intermediate breaks, most of the nitrogen gas is expelled at the break and almost no nitrogen gas is trapped in the SGs. In comparison with the cases calculated without taking into account the release of nitrogen gas, the start of the LPIS is delayed by between 1 and 1.75 h. Applicability of the obtained results to the real safety conditions must take into accountthe real operating procedures used in the nuclear power plant.

Converter-flux-based current control of voltage source PWM rectifiers - analysis and implementation

Pulsewidth-modulated (PWM) rectifier technology is increasingly used in industrial applications like variable-speed motor drives, since it offers several desired features such as sinusoidal input currents, controllable power factor, bidirectional power flow and high quality DC output voltage. To achieve these features,however, an effective control system with fast and accurate current and DC voltage responses is required. From various control strategies proposed to meet these control objectives, in most cases the commonly known principle of the synchronous-frame current vector control along with some space-vector PWM scheme have been applied. Recently, however, new control approaches analogous to the well-established direct torque control (DTC) method for electrical machines have also emerged to implement a high-performance PWM rectifier. In this thesis the concepts of classical synchronous-frame current control and DTC-based PWM rectifier control are combined and a new converter-flux-based current control (CFCC) scheme is introduced. To achieve sufficient dynamic performance and to ensure a stable operation, the proposed control system is thoroughly analysed and simple rules for the controller design are suggested. Special attention is paid to the estimationof the converter flux, which is the key element of converter-flux-based control. Discrete-time implementation is also discussed. Line-voltage-sensorless reactive reactive power control methods for the L- and LCL-type line filters are presented. For the L-filter an open-loop control law for the d-axis current referenceis proposed. In the case of the LCL-filter the combined open-loop control and feedback control is proposed. The influence of the erroneous filter parameter estimates on the accuracy of the developed control schemes is also discussed. A newzero vector selection rule for suppressing the zero-sequence current in parallel-connected PWM rectifiers is proposed. With this method a truly standalone and independent control of the converter units is allowed and traditional transformer isolation and synchronised-control-based solutions are avoided. The implementation requires only one additional current sensor. The proposed schemes are evaluated by the simulations and laboratory experiments. A satisfactory performance and good agreement between the theory and practice are demonstrated.

On Modelling, System Identification and Control of Servo-Systems with a Flexible Load

The present study was done with two different servo-systems. In the first system, a servo-hydraulic system was identified and then controlled by a fuzzy gainscheduling controller. The second servo-system, an electro-magnetic linear motor in suppressing the mechanical vibration and position tracking of a reference model are studied by using a neural network and an adaptive backstepping controller respectively. Followings are some descriptions of research methods. Electro Hydraulic Servo Systems (EHSS) are commonly used in industry. These kinds of systems are nonlinearin nature and their dynamic equations have several unknown parameters.System identification is a prerequisite to analysis of a dynamic system. One of the most promising novel evolutionary algorithms is the Differential Evolution (DE) for solving global optimization problems. In the study, the DE algorithm is proposed for handling nonlinear constraint functionswith boundary limits of variables to find the best parameters of a servo-hydraulic system with flexible load. The DE guarantees fast speed convergence and accurate solutions regardless the initial conditions of parameters. The control of hydraulic servo-systems has been the focus ofintense research over the past decades. These kinds of systems are nonlinear in nature and generally difficult to control. Since changing system parameters using the same gains will cause overshoot or even loss of system stability. The highly non-linear behaviour of these devices makes them ideal subjects for applying different types of sophisticated controllers. The study is concerned with a second order model reference to positioning control of a flexible load servo-hydraulic system using fuzzy gainscheduling. In the present research, to compensate the lack of dampingin a hydraulic system, an acceleration feedback was used. To compare the results, a pcontroller with feed-forward acceleration and different gains in extension and retraction is used. The design procedure for the controller and experimental results are discussed. The results suggest that using the fuzzy gain-scheduling controller decrease the error of position reference tracking. The second part of research was done on a PermanentMagnet Linear Synchronous Motor (PMLSM). In this study, a recurrent neural network compensator for suppressing mechanical vibration in PMLSM with a flexible load is studied. The linear motor is controlled by a conventional PI velocity controller, and the vibration of the flexible mechanism is suppressed by using a hybrid recurrent neural network. The differential evolution strategy and Kalman filter method are used to avoid the local minimum problem, and estimate the states of system respectively. The proposed control method is firstly designed by using non-linear simulation model built in Matlab Simulink and then implemented in practical test rig. The proposed method works satisfactorily and suppresses the vibration successfully. In the last part of research, a nonlinear load control method is developed and implemented for a PMLSM with a flexible load. The purpose of the controller is to track a flexible load to the desired position reference as fast as possible and without awkward oscillation. The control method is based on an adaptive backstepping algorithm whose stability is ensured by the Lyapunov stability theorem. The states of the system needed in the controller are estimated by using the Kalman filter. The proposed controller is implemented and tested in a linear motor test drive and responses are presented.

Design of axial-flux permanent-magnet low-speed machines and performance comparison between radial-flux and axial-flux machines

This thesis presents an alternative approach to the analytical design of surface-mounted axialflux permanent-magnet machines. Emphasis has been placed on the design of axial-flux machines with a one-rotor-two-stators configuration. The design model developed in this study incorporates facilities to include both the electromagnetic design and thermal design of the machine as well as to take into consideration the complexity of the permanent-magnet shapes, which is a typical requirement for the design of high-performance permanent-magnet motors. A prototype machine with rated 5 kW output power at 300 min-1 rotation speed has been designed and constructed for the purposesof ascertaining the results obtained from the analytical design model. A comparative study of low-speed axial-flux and low-speed radial-flux permanent-magnet machines is presented. The comparative study concentrates on 55 kW machines with rotation speeds 150 min-1, 300 min-1 and 600 min-1 and is based on calculated designs. A novel comparison method is introduced. The method takes into account the mechanical constraints of the machine and enables comparison of the designed machines, with respect to the volume, efficiency and cost aspects of each machine. It is shown that an axial-flux permanent-magnet machine with one-rotor-two-stators configuration has generally a weaker efficiency than a radial-flux permanent-magnet machine if for all designs the same electric loading, air-gap flux density and current density have been applied. On the other hand, axial-flux machines are usually smaller in volume, especially when compared to radial-flux machines for which the length ratio (axial length of stator stack vs. air-gap diameter)is below 0.5. The comparison results show also that radial-flux machines with alow number of pole pairs, p < 4, outperform the corresponding axial-flux machines.

Analysis of torque and speed ripple producing non-idealities of frequency converters in electric drives

Electric motors driven by adjustable-frequency converters may produce periodic excitation forces that can cause torque and speed ripple. Interaction with the driven mechanical system may cause undesirable vibrations that affect the system performance and lifetime. Direct drives in sensitive applications, such as elevators or paper machines, emphasize the importance of smooth torque production. This thesis analyses the non-idealities of frequencyconverters that produce speed and torque ripple in electric drives. The origin of low order harmonics in speed and torque is examined. It is shown how different current measurement error types affect the torque. As the application environment, direct torque control (DTC) method is applied to permanent magnet synchronous machines (PMSM). A simulation model to analyse the effect of the frequency converter non-idealities on the performance of the electric drives is created. Themodel enables to identify potential problems causing torque vibrations and possibly damaging oscillations in electrically driven machine systems. The model is capable of coupling with separate simulation software of complex mechanical loads. Furthermore, the simulation model of the frequency converter's control algorithm can be applied to control a real frequency converter. A commercial frequencyconverter with standard software, a permanent magnet axial flux synchronous motor and a DC motor as the load are used to detect the effect of current measurement errors on load torque. A method to reduce the speed and torque ripple by compensating the current measurement errors is introduced. The method is based on analysing the amplitude of a selected harmonic component of speed as a function oftime and selecting a suitable compensation alternative for the current error. The speed can be either measured or estimated, so the compensation method is applicable also for speed sensorless drives. The proposed compensation method is tested with a laboratory drive, which consists of commercial frequency converter hardware with self-made software and a prototype PMSM. The speed and torque rippleof the test drive are reduced by applying the compensation method. In addition to the direct torque controlled PMSM drives, the compensation method can also beapplied to other motor types and control methods.

Transfer entropy reconstruction and labeling of neuronal connections from simulated calcium imaging

Neuronal dynamics are fundamentally constrained by the underlying structural network architecture, yet much of the details of this synaptic connectivity are still unknown even in neuronal cultures in vitro. Here we extend a previous approach based on information theory, the Generalized Transfer Entropy, to the reconstruction of connectivity of simulated neuronal networks of both excitatory and inhibitory neurons. We show that, due to the model-free nature of the developed measure, both kinds of connections can be reliably inferred if the average firing rate between synchronous burst events exceeds a small minimum frequency. Furthermore, we suggest, based on systematic simulations, that even lower spontaneous inter-burst rates could be raised to meet the requirements of our reconstruction algorithm by applying a weak spatially homogeneous stimulation to the entire network. By combining multiple recordings of the same in silico network before and after pharmacologically blocking inhibitory synaptic transmission, we show then how it becomes possible to infer with high confidence the excitatory or inhibitory nature of each individual neuron.

Malignant metastasizing solitary fibrous tumors of the liver: a report of three cases.

Solitary fibrous tumors are rare neoplasms of mesenchymal origin that have been reported in various other extrathoracic sites, including the liver. We present a case series of three malignant solitary fibrous tumors of the liver, occurring in two women 74 and 80 years old and one 65-year-old man. No clinical features were predictive of malignancy except the large sizes and synchronous presence of lung metastases in two of the three cases. Histological examinations revealed the presence of high pleomorphic cellularity with nuclear atypia, necrosis and high mitotic ratios. All patients died of disease progression.