A recombinant bovine herpesvirus 5 defective in thymidine kinase and glycoprotein E is attenuated and immunogenic for calves

Bovine herpesvirus 5 (BoHV-5) is an important pathogen of cattle in South America and efforts have been made to produce safer and more effective vaccines. In addition to afford protection, herpesvirus vaccines should allow serological differentiation of vaccinated from naturally, latently infected animals. We previously reported the construction and characterization in vitro of a double mutant BoHV-5 (BoHV-5gE/TK Δ) lacking the genes encoding thymidine kinase (tk) for attenuation, and glycoprotein E (gE) as the antigenic marker, as a vaccine candidate strain (Brum et al. 2010a). The present article reports an investigation on the attenuation and immunogenicity of this recombinant in calves. In a first experiment, 80 to 90-day-old seronegative calves (n=6) inoculated intranasally with the recombinant (titer of 10(7.5)TCID50) shed virus in low to moderate titers in nasal secretions for up to 6 days, yet did not develop any respiratory, systemic or neurological signs of infection. At day 30 post-infection (pi) all calves had BoHV-5 specific neutralizing (VN) antibodies in titers of 4 to 8 and were negative for anti-gE antibodies in a commercial ELISA test. Administration of dexamethasone (0.1mg/kg/day during 5 days) to four of these calves at day 42 pi did not result in virus shedding or increase in VN titers, indicating lack of viral reactivation. Secondly, a group of 8-month-old calves (n=9) vaccinated intramuscularly (IM) with the recombinant virus (10(7.5)TCID50/animal) did not shed virus in nasal secretions, remained healthy and developed VN titers from 2 to 8 at day 42 post-vaccination (pv), remaining negative for gE antibodies. Lastly, 21 calves (around 10 months old) maintained under field conditions were vaccinated IM with the recombinant virus (titer of 10(7.3)TCID50). All vaccinated animals developed VN titers from 2 to 16 at day 30 pv. A boost vaccination performed at day 240 pv resulted in a rapid and strong anamnestic antibody response, with VN titers reaching from 16 to 256 at day 14 post-booster. Again, serum samples remained negative for gE antibodies. Selected serum samples from vaccinated animals showed a broad VN activity against nine BoHV-5 and eight BoHV-1 field isolates. These results show that the recombinant virus is attenuated, immunogenic for calves and induces an antibody response differentiable from that induced by natural infection. Thus, the recombinant BoHV-5gE/TKΔ is an adequate candidate strain for a modified live vaccine.

Seroprevalence and risk factors associated with Chlamydophila abortus infection in dairy goats in the Northeast of Brazil

Few data are available on the prevalence and risk factors of Chlamydophila abortus infection in goats in Brazil. A cross-sectional study was carried out to determine the flock-level prevalence of C. abortus infection in goats from the semiarid region of the Paraíba State, Northeast region of Brazil, as well as to identify risk factors associated with the infection. Flocks were randomly selected and a pre-established number of female goats > 12 mo old were sampled in each of these flocks. A total of 975 serum samples from 110 flocks were collected, and structured questionnaire focusing on risk factors for C. abortus infection was given to each farmer at the time of blood collection. For the serological diagnosis the complement fixation test (CFT) using C. abortus S26/3 strain as antigen was performed. The flock-level factors for C. abortus prevalence were tested using multivariate logistic regression model. Fifty-five flocks out of 110 presented at least one seropositive animal with an overall prevalence of 50.0% (95%; CI: 40.3%, 59.7%). Ninety-one out of 975 dairy goats examined were seropositive with titers >32, resulting in a frequency of 9.3%. Lend buck for breeding (odds ratio = 2.35; 95% CI: 1.04-5.33) and history of abortions (odds ratio = 3.06; 95% CI: 1.37-6.80) were associated with increased flock prevalence.

Kaksisuuntaisen DC/DC-hakkurin virtasäätö polttokennosovelluksessa

Ilmastonmuutos ja fossiilisten polttoaineiden ehtyminen ovat edesauttaneet uusiutuvien energialähteiden tutkimusta huomattavasti. Lisäksi alati kasvava sähköenergian tarve lisää hajautetun sähköntuotannon ja vaihtoehtoisten energialähteiden kiinnostavuutta. Yleisimpiä hajautetun sähköntuotannon energialähteitä ovat tuulivoima, aurinkovoima ja uutena tulokkaana polttokennot. Polttokennon kytkeminen sähköverkkoon vaatii tehoelektroniikkaa, ja yleensä yksinkertaisessa polttokennosovelluksessa polttokenno kytketään galvaanisesti erottavan yksisuuntaisen DC/DC-hakkurin ja vaihtosuuntaajan kanssa sarjaan. Polttokennon rinnalla voidaan käyttää akkua tasaamaan polttokennon syöttämää jännitettä, jolloin akun ja polttokennon väliin tarvitaan kaksisuuntainen DC/DC-hakkuri, joka pystyy siirtämään energiaa molempiin suuntiin. Tässä diplomityössä on esitetty kaksisuuntaisen DC/DC-hakkurin tilayhtälökeskiarvoistusmenetelmään perustuva malli sekä mallin perusteella toteutettu virtasäätö. Tutkittava hakkuritopologia on kokosilta-tyyppinen boost-hakkuri, ja säätömenetelmä keskiarvovirtasäätö. Työn tuloksena syntyi tilayhtälömalli kaksisuuntaiselle FB boost -hakkurille sekä sen tulokelan virran säätämiseen soveltuva säädin. Säädin toimii normaalitilanteissa hyvin, mutta erikoistilanteissa, kuten hakkurin tulojännitteen äkillisessä muutostilanteessa, vaadittaisiin tehokkaampi säädin, jolla saavutettaisiin nopeampi nousuaika ilman ylitystä ja oskillointia.

Nettobudjetoinnin implementointi kunnallisessa yksikössä - Case: Helsingin kaupungin liikuntavirasto

Julkisen sektorin organisaatioita on kritisoitu niiden tehottomuudesta palveluiden tuottajina ja kritiikki on lisännyt keskustelua julkisen ja yksityisen sektorin sopivasta suhteesta. Julkisen sektorin organisaatioissa tilanteeseen on herätty ja toiminnan tehostamiseen on alettu etsiä keinoja. New Public Management:in ja tulosjohtamisen ajatusmaailma ovat ottaneet jalansijaa julkisen sektorin johtamisessa ja samalla tuoneet mukanaan entistä tulospainotteisempaa ajattelutapaa. Helsingin kaupungin liikuntavirastolla siirryttiin bruttobudjetoinnista nettobudjetointiin vuoden 2013 alusta. Budjetointimenetelmän muutoksen taustalla vaikuttaa tavoite viraston toiminnan tehostamisesta. Tutkimus keskittyy selvittämään liikuntaviraston muutosprosessia ja uuden budjetointimenetelmän implementointia. Tutkimuksen tavoitteena on luoda työkalu helpottamaan nettobudjetoinnin implementointia. Tutkimuksen empiirinen aineisto kerättiin puolistrukturoitujen haastattelujen avulla, jotka suoritettiin joulukuun 2012 ja huhtikuun 2013 välillä. Empiiriseen aineistoon ja muutosjohtamisen teoriaan nojaten tutkimuksessa onnistuttiin luomaan liikuntavirastolle muutosprosessin vaihemalli, joka sisältää toimenpide-ehdotuksia muutoksen ja uuden budjetointimenetelmän implementoinnin helpottamiseksi.

Aktiivisen verkkosillan tuottaman yhteismuotoisen jännitteen vaimentaminen kaksitasoisessa, jännitevälipiirillisessä, taajuusmuuttajatopologiassa

Pulssinleveysmoduloidun vaihtosuuntaajan hyötysuhteen parantaminen ja kytkentätaajuuden suurentaminen ovat johtaneet lähtöjännitteen suuritaajuiseen taajuussisältöön kaksitasoisessa, jännitevälipiirillisessä taajuusmuuttajatopologiassa. Kasvava tarve siirtää tehoa myös verkkoon päin on lisännyt aktiivisen verkkosillan käyttöä. Kaksitasoisen aktiivisen verkkosillan vaikutuksesta DC-välipiirin keskipisteen ja kolmivaiheisen kuorman tähtipisteen välinen jännite on nollasta poikkeava aiheuttaen suurentuneen yhteismuotoisen jännitteen taajuusmuuttajan lähtöön ja verkon puolelle. Lisäksi yhteismuotoisten jännitteiden aiheuttamat kytkentätaajuiset häiriövirrat voivat aiheuttaa vikavirtasuojien tahatonta laukeamista, vaikeuttaa EMC-standardien vaatimusten täyttämistä, lisätä moottorin käämieristyksien rasitusta ja mahdollisuutta moottorin laakerivaurioille. Diplomityössä tutkitaan aktiivisen ja passiivisen verkkosillan tuottamaa yhteismuotoista jännitettä simuloinneilla. Esitellään aikaisempaa tutkimustietoa yhteismuotoisen jännitteen ja virran vaimennusratkaisuista aktiivista verkkosiltaa käytettäessä. Tutkimustiedon pohjalta suunnitellaan koelaitteistolle soveltuva suodin. Suotimen toiminta testataan simuloinnein sekä kokeellisin mittauksin. Tehdyt mittaukset osoittavat, että suunniteltu suodin vaimentaa yhteismuotoista jännitettä noin 20 dB verkkosillan kytkentätaajuudella ja tämän jälkeen yli 20 dB/dekadi taajuuteen 100 kHz asti. Lisäksi yhteismuotoisen virran suuruus syöttökaapelin kautta pieneni ehdotetun suotimen vaikutuksesta.

Modeling and Parameter Estimation of Double-Star Permanent Magnet Synchronous Machines

The power rating of wind turbines is constantly increasing; however, keeping the voltage rating at the low-voltage level results in high kilo-ampere currents. An alternative for increasing the power levels without raising the voltage level is provided by multiphase machines. Multiphase machines are used for instance in ship propulsion systems, aerospace applications, electric vehicles, and in other high-power applications including wind energy conversion systems. A machine model in an appropriate reference frame is required in order to design an efficient control for the electric drive. Modeling of multiphase machines poses a challenge because of the mutual couplings between the phases. Mutual couplings degrade the drive performance unless they are properly considered. In certain multiphase machines there is also a problem of high current harmonics, which are easily generated because of the small current path impedance of the harmonic components. However, multiphase machines provide special characteristics compared with the three-phase counterparts: Multiphase machines have a better fault tolerance, and are thus more robust. In addition, the controlled power can be divided among more inverter legs by increasing the number of phases. Moreover, the torque pulsation can be decreased and the harmonic frequency of the torque ripple increased by an appropriate multiphase configuration. By increasing the number of phases it is also possible to obtain more torque per RMS ampere for the same volume, and thus, increase the power density. In this doctoral thesis, a decoupled d–q model of double-star permanent-magnet (PM) synchronous machines is derived based on the inductance matrix diagonalization. The double-star machine is a special type of multiphase machines. Its armature consists of two three-phase winding sets, which are commonly displaced by 30 electrical degrees. In this study, the displacement angle between the sets is considered a parameter. The diagonalization of the inductance matrix results in a simplified model structure, in which the mutual couplings between the reference frames are eliminated. Moreover, the current harmonics are mapped into a reference frame, in which they can be easily controlled. The work also presents methods to determine the machine inductances by a finite-element analysis and by voltage-source inverters on-site. The derived model is validated by experimental results obtained with an example double-star interior PM (IPM) synchronous machine having the sets displaced by 30 electrical degrees. The derived transformation, and consequently, the decoupled d–q machine model, are shown to model the behavior of an actual machine with an acceptable accuracy. Thus, the proposed model is suitable to be used for the model-based control design of electric drives consisting of double-star IPM synchronous machines.

Jännitettä nostavan hakkurin käyttö akkukäyttöisessä audiolaitteessa

Audiovahvistimet pohjautuvat yhä useammin D-luokan vahvistimiin niiden korkean hyötysuhteen takia. Tämä mahdollistaa pidemmän käyttöajan tai vastaavasti tehon lisäämisen kannettavissa audiolaitteissa. Kuitenkin, jotta akkukäyttöisestä audiolaitteesta saataisiin suurempaa tehoa, se vaatii yleensä korkeamman jännitteen kuin yksittäisen akun lähtöjännite on. Korkeampi jännite voidaan saavuttaa lisäämällä akkuja tai käyttämällä jännitettä nostavaa hakkuria. Hakkureissa syntyy kuitenkin kytkennästä johtuvaa värettä, mille D-luokan vahvistimet ovat alttiita. Tässä työssä tutkitaan boost- ja Čuk-hakkurin soveltuvuutta jännitteen nostoon akkukäyttöisessä audiolaitteessa. Käytännön sovelluksena toimii Porsas, josta halutaan saada 500 W teho. Työssä tutkitaan audiolaitteen asettamia ehtoja jännitelähteelle sekä hakkurien mitoittamista ehtojen mukaisesti. Työn tutkimustapana on kirjallisuustutkimus ja simulointi. Audiolaitteen jännitelähteeltä vaatima teho vaihtelee suuresti. Tämä tulee ottaa huomioon hakkurin komponenttien mitoituksessa. Lisäksi hakkurin lähtöjännitteen väre pyritään minimoimaan, koska sillä on suuri vaikutus vahvistimen toimintaan. Tulovirran väreen minimoinnilla on pidentävä vaikutus akun purkusykliin. Hakkurien laskennalliset komponenttien arvot sekä simuloinnit osoittavat, että hakkurit olisivat myös mahdollista tehdä käytännössä. Simulointien perusteella boost-hakkurin komponenttien arvot ovat pienempiä kuin Čuk-hakkurin. Boost-hakkurille löytyy myös valmiita ohjainpiirejä enemmän. Toisaalta Čuk-hakkurilla on mahdollista tehdä myös energiansäästötila. Hakkurien ohjaus ja jäähdytys vaatisivat jatkotutkimusta.

Kestomagneettitahtikonekäyttöjen erot

Permanent magnet drives with nominal power over 10 kW were not a cost-sufficient system 25 years ago due to high material expenses. The improvements in motor drives, the rise in competition and the tightening of standards and regulations have caused that the PM-drives are more and more common in the over 10 kW nominal power range. The goal of this thesis is to research the performance in relation to nominal power of a PM-drive technique that is vastly increasing its popularity in fan related devices. The studied motor technique brushless direct current drive (BLDC) consists of a voltage source inverter, permanent motor and six-step-control. The reference drive is a brushless alternating current drive (BLAC) which consists of a VSI, PM and a hysteresis control. As a conclusion there are no major obstacles that would impede the BLDC-drive technique from expanding to larger power stages. The following factors must be taken into consideration when designing a BLDC-drive: motor’s current change rate, inverter switching frequency, motor’s nominal electric frequency, phase inductance and the current handling capability of the inverter. The fluctuating material costs create instability to the end prices of PM-motors that can in the worst case lead to diminished interest towards BLDC- and PM-drives in general.

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.

Interruption of recently induced immune responses by oral administration of antigen

Interest in oral tolerance has been renewed in the last few years as a possibility of intervention in human autoimmune diseases. An obstacle in this direction is that, although easily induced in animals virgin of contact with the antigen, oral tolerance becomes hard to induce in previously immunized animals. The present results show that there is an early period after primary immunization in which prolonged oral exposure to the antigen may arrest ongoing immune responses. Beyond this period, oral exposures to the antigen become ineffective and may actually boost immune responses. The end of the susceptible period coincides with the emergence of free specific antibodies in serum. However, the previous administration of purified anti-ovalbumin antibodies (40 µg) was unable to block the induction of oral tolerance to ovalbumin in normal mice

Minimizing Conducted RF-Emissions in Switch Mode Power Supplies Using Spread-Spectrum Techniques

Switching power supplies are usually implemented with a control circuitry that uses constant clock frequency turning the power semiconductor switches on and off. A drawback of this customary operating principle is that the switching frequency and harmonic frequencies are present in both the conducted and radiated EMI spectrum of the power converter. Various variable-frequency techniques have been introduced during the last decade to overcome the EMC problem. The main objective of this study was to compare the EMI and steady-state performance of a switch mode power supply with different spread-spectrum/variable-frequency methods. Another goal was to find out suitable tools for the variable-frequency EMI analysis. This thesis can be divided into three main parts: Firstly, some aspects of spectral estimation and measurement are presented. Secondly, selected spread spectrum generation techniques are presented with simulations and background information. Finally, simulations and prototype measurements from the EMC and the steady-state performance are carried out in the last part of this work. Combination of the autocorrelation function, the Welch spectrum estimate and the spectrogram were used as a substitute for ordinary Fourier methods in the EMC analysis. It was also shown that the switching function can be used in preliminary EMC analysis of a SMPS and the spectrum and autocorrelation sequence of a switching function correlates with the final EMI spectrum. This work is based on numerous simulations and measurements made with the prototype. All these simulations and measurements are made with the boost DC/DC converter. Four different variable-frequency modulation techniques in six different configurations were analyzed and the EMI performance was compared to the constant frequency operation. Output voltage and input current waveforms were also analyzed in time domain to see the effect of the spread spectrum operation on these quantities. According to the results presented in this work, spread spectrum modulation can be utilized in power converter for EMI mitigation. The results from steady-state voltage measurements show, that the variable-frequency operation of the SMPS has effect on the voltage ripple, but the ripple measured from the prototype is still acceptable in some applications. Both current and voltage ripple can be controlled with proper main circuit and controller design.

Minimizing Circulating Current in Parallel-Connected Photovoltaic Inverters

Parallel-connected photovoltaic inverters are required in large solar plants where it is not economically or technically reasonable to use a single inverter. Currently, parallel inverters require individual isolating transformers to cut the path for the circulating current. In this doctoral dissertation, the problem is approached by attempting to minimize the generated circulating current. The circulating current is a function of the generated common-mode voltages of the parallel inverters and can be minimized by synchronizing the inverters. The synchronization has previously been achieved by a communication link. However, in photovoltaic systems the inverters may be located far apart from each other. Thus, a control free of communication is desired. It is shown in this doctoral dissertation that the circulating current can also be obtained by a common-mode voltage measurement. A control method based on a short-time switching frequency transition is developed and tested with an actual photovoltaic environment of two parallel inverters connected to two 5 kW solar arrays. Controls based on the measurement of the circulating current and the common-mode voltage are generated and tested. A communication-free method of controlling the circulating current between parallelconnected inverters is developed and verified.

Recombinant viruses as vaccines against viral diseases

Vaccine approaches to infectious diseases are widely applied and appreciated. Amongst them, vectors based on recombinant viruses have shown great promise and play an important role in the development of new vaccines. Many viruses have been investigated for their ability to express proteins from foreign pathogens and induce specific immunological responses against these antigens in vivo. Generally, gene-based vaccines can stimulate potent humoral and cellular immune responses and viral vectors might be an effective strategy for both the delivery of antigen-encoding genes and the facilitation and enhancement of antigen presentation. In order to be utilized as a vaccine carrier, the ideal viral vector should be safe and enable efficient presentation of required pathogen-specific antigens to the immune system. It should also exhibit low intrinsic immunogenicity to allow for its re-administration in order to boost relevant specific immune responses. Furthermore, the vector system must meet criteria that enable its production on a large-scale basis. Several viral vaccine vectors have thus emerged to date, all of them having relative advantages and limits depending on the proposed application, and thus far none of them have proven to be ideal vaccine carriers. In this review we describe the potential, as well as some of the foreseeable obstacles associated with viral vaccine vectors and their use in preventive medicine.

N-terminal-pro-brain natriuretic peptide, but not brain natriuretic peptide, is increased in patients with severe obesity

Elevated body mass index (BMI) has been reported as a risk factor for heart failure. Prevention of heart failure through identification and management of risk factors and preclinical phases of the disease is a priority. Levels of natriuretic peptides as well as activity of their receptors have been found altered in obese persons with some conflicting results. We investigated cardiac involvement in severely obese patients by determining N-terminal-pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) and attempting to correlate the levels of these peptides in serum and plasma, respectively, with BMI, duration of obesity, waist circumference, and echocardiographic parameters. Thirty-three patients with severe obesity (mean BMI: 46.39 kg/m², mean age: 39 years) were studied. The control group contained 30 healthy age-matched individuals (BMI: <25 kg/m², mean age: 43 years). The t-test and Spearman correlation were used for statistical analysis. Log-NT-proBNP was significantly higher (P = 0.003) in obese patients (mean 1.67, 95% CI: 1.50-1.83 log pg/mL) compared to controls (mean: 1.32, 95% CI: 1.17-1.47 log pg/mL). The Log-NT-proBNP concentration correlated with duration of obesity (r = 0.339, P < 0.004). No difference was detected in the Log-BNP concentration (P = 0.63) of obese patients (mean: 0.73, 95% CI: 0.46-1.00 log pg/mL) compared to controls (mean: 0.66, 95% CI: 0.51-0.81 log pg/mL). NT-proBNP, but not BNP, is increased in severely obese patients and its concentration in serum is correlated with duration of obesity. NT-proBNP may be useful as an early diagnostic tool for the detection of cardiac burden due to severe obesity.

Modular Double-Cascade Converter

Medium-voltage motor drives extend the power rating of AC motor drives in industrial applications. Multilevel converters are gaining an ever-stronger foothold in this field. This doctoral dissertation introduces a new topology to the family of modular multilevel converters: the modular double-cascade converter. The modularity of the converter is enabled by the application of multiwinding mediumfrequency isolation transformers. Owing to the innovative transformer link, the converter presents many advantageous properties at a concept level: modularity, high input and output power quality, small footprint, and wide variety of applications, among others. Further, the research demonstrates that the transformer link also plays a key role in the disadvantages of the topology. An extensive simulation study on the new converter is performed. The focus of the simulation study is on the development of control algorithms and the feasibility of the topology. In particular, the circuit and control concepts used in the grid interface, the coupling configurations of the load inverter, and the transformer link operation are thoroughly investigated. Experimental results provide proof-of-concept results on the operation principle of the converter. This work concludes a research collaboration project on multilevel converters between LUT and Vacon Plc. The project was active from 2009 until 2014.