Targeting Adenoviral Gene Therapy Vectors to Head and Neck Squamous Cell Carcinoma and Heart

Gene therapy aims to treat diseases by introducing genetic material to the diseased tissue. For cancer treatment it is important to destroy cancerous cells; this can be achieved by introducing a gene, which induces cell death or by allowing viral vectors to replicate, which also results in destruction of cancerous cells. For cardiac diseases the approach is more like the former, except the gene produces beneficial effects, like angiogenesis. Adenoviruses have many beneficial qualities, which make the virus an interesting gene therapy vector; it can be produced relatively easily, its manipulation is quite easy and it has naturally broad tropism. By removing or replacing certain genes in the adenoviral genome, it can be made non-replicative. In this study, adenoviral receptor expression patterns were characterized in both head and neck squamous cell carcinoma and the human heart. Adenovirus serotype 5 receptor expression in head and neck cancer cell lines was found to be highly variable between cell lines and overall at lower levels, while Ad35 receptor expression was more uniform and at higher levels in all analyzed cell lines. It was also shown that a hybrid virus Ad5/35 is able to infect cells refractory to Ad5, which correlates with receptor expression in these cells. Furthermore, this difference in infection properties extends to cell killing efficiency in case of conditionally replicative viruses. Expression levels of adenoviral receptors CAR, CD46, CD86 and αv-integrins were found to be high both in normal and dilated cardiomyopathy heart tissue. The receptor levels also correlate with transduction efficiency after intracardiac injection. Ad5 showed superior transduction ability compared with Ad5/35, but evoked also a more profound immune reaction when administered this way. Adenoviral gene therapy vectors are the most used delivery vehicles in clinical trials to date. These vectors have proven to be well tolerated and positive results have been obtained when combined with traditional treatments, although poor transduction efficiency has often been reported due to low-level expression of viral receptors on target cells. In spite of this, the results are encouraging and merit for further research.

Pyörivien sähkökoneiden kotelointia koskevat standardit ja aksiaalivuokoneen jäähdytyksen kehittäminen

Tämä diplomityö on osa Lappeenrannan teknillisen yliopiston ja Visedo Oy:n yhteistyöprojektia. Työssä selvitetään pyörivien sähkökoneiden kotelointeja koskevia standardeja ja niiden vaikutukset koneiden suunnittelulle ja valmistukselle. Lisäksi työssä käsitellään aksiaalivuokoneen jäähdytykseen liittyviä ongelmia, kehitetään koneen nykyisiä jäähdytysratkaisuja ja ideoidaan käytettävissä olevia uusia jäähdytysmenetelmiä. Kehitysideoiden rajoitteena toimii koneelta vaadittu kotelointiluokka IP 64 – IP 68 sekä koneelle määritetty kestomagnetoitu aksiaalivuorakenne. Sähkökoneiden kotelointeja koskevien standardien asettamien vaatimusten määrittäminen tapahtui suurilta osin kirjallisuusselvityksenä. Standardien vaikutukset koneiden suunnittelulle ja valmistettavuudelle on selvitetty standardien kotelointien rakenteelle asettamien vaatimusten perusteella. Aksiaalivuokoneen jäähdytysongelmien selvittäminen, käytössä olevien jääh-dytysratkaisujen kehittäminen ja uusien menetelmien ideointi suoritettiin projektiluontoisesti yhdessä eri alojen asiantuntijoista koostuvan jäähdytystyöryhmän kanssa. Työn tuloksena laadittiin Visedo Oy:lle standardikäsikirja, jonka avulla Visedon sähkökoneiden tuoteperheeseen kuuluvien koneiden suunnitteluvaiheessa voidaan varmistaa koneiden standardienmukaisuus. Käsikirjassa on myös esitetty huomioita eri kotelointiluokkien asettamista vaatimuksista koneiden valmistukselle. Aksiaalivuokoneiden jäähdytykseen liittyen tavoitteena oli ratkaista aksiaalivuokoneisiin liittyviä jäähdytysongelmia. Työn tuloksena saa-tiin selville aksiaalivuokoneissa jäähdytyksen kehittämistä vaativat kohteet, laadittiin nykyisten jäähdytysratkaisujen parannusehdotuksia ja kehitettiin täysin uusia jäähdytysmenetelmiä.

Usability of laser–arc hybrid welding processes in industrial applications

Metal industries producing thick sections have shown increasing interest in the laser–arc hybrid welding process because of its clear advantages compared with the individual processes of autogenous laser welding and arc welding. One major benefit of laser–arc hybrid welding is that joints with larger gaps can be welded with acceptable quality compared to autogenous laser welding. The laser-arc hybrid welding process has good potential to extend the field of applications of laser technology, and provide significant improvements in weld quality and process efficiency in manufacturing applications. The objective of this research is to present a parameter set-up for laser–arc hybrid welding processes, introduce a methodical comparison of the chosen parameters, and discuss how this technology may be adopted in industrial applications. The research describes the principles, means and applications of different types of laser–arc hybrid welding processes. Conducted experiment processing variables are presented and compared using an analytical model which can also be used for predictive simulations. The main argument in this thesis is that profound understanding of the advanced technology of laser-arc hybrid welding will help improve the productivity of welding in industrial applications. Based on a review of the current knowledge base, important areas for further research are also identified. This thesis consists of two parts. The first part introduces the research topic and discusses laser–arc hybrid welding by characterizing its mechanism and most important variables. The second part comprises four research papers elaborating on the performance of laser– arc hybrid welding in the joining of metals. The study uses quantitative and qualitative research methods which include in-depth, interpretive analyses of results from a number of research groups. In the interpretive analysis, the emphasis is placed on the relevance and usefulness of the investigative results drawn from other research publications. The results of this study contribute to research on laser–arc hybrid welding by increasing understanding of how old and new perspectives on laser–arc hybrid welding are evidenced in industry. The research methodology applied permits continued exploration of how laser–arc hybrid welding and various process factors influence the overall quality of the weld. Thestudy provides a good foundation for future research, creates improved awareness of the laser–arc hybrid welding process, and assists the metal industry to maximize welding productivity.

Design of marine generators for alternative diesel-electric power systems

This study compares different electric propulsion systems. Results of the analysis of all the advantages and disadvantages of the different propulsion systems are given. This thesis estimates possibilities to apply different diesel-electric propulsion concepts for different vessel types. Small and medium size vessel’s power ranges are studied. The optimal delivery system is chosen. This choice is made on the base of detailed study of the concepts, electrical equipment market and comparison of mass, volume and efficiency parameters. In this thesis three marine generators are designed. They are: salient pole synchronous generator and two permanent magnet synchronous generators. Their electrical, dimensional, cost and efficiency parameters are compared. To understand all the benefits diagrams with these parameters are prepared. Possible benefits and money savings are estimated. As the result the advantages, disadvantages and boundary conditions for the permanent magnet synchronous generator application in marine electric-power systems are found out.

Electric-drive-based control and electric energy regeneration in a hydraulic system

Over the recent years, development in mobile working machines has concentrated on reducing emissions owing to the tightening rules and needs to improve energy utilization and reduce power losses. This study focuses on energy utilization and regeneration in an electro-hydraulic forklift, which is a lifting equipment application. The study starts from the modelling and simulation of a hydraulic forklift. The energy regeneration from the potential energy of the load was studied. Also a flow-based electric motor speed control was suggested in this thesis instead of the throttle control method or the variable displacement pump control. Topics related to further development in the future are discussed. Finally, a summary and conclusions are presented.

Lethal weapons : novel approaches for receptor-targeted cancer cell elimination

The currently used forms of cancer therapy are associated with drug resistance and toxicity to healthy tissues. Thus, more efficient methods are needed for cancer-specific induction of growth arrest and programmed cell death, also known as apoptosis. Therapeutic forms of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) are investigated in clinical trials due to the capability of TRAIL to trigger apoptosis specifically in cancer cells by activation of cell surface death receptors. Many tumors, however, have acquired resistance to TRAIL-induced apoptosis and sensitizing drugs for combinatorial treatments are, therefore, in high demand. This study demonstrates that lignans, natural polyphenols enriched in seeds and cereal, have a remarkable sensitizing effect on TRAIL-induced cell death at non-toxic lignan concentrations. In TRAIL-resistant and androgen-dependent prostate cancer cells we observe that lignans repress receptor tyrosine kinase (RTK) activity and downregulate cell survival signaling via the Akt pathway, which leads to increased TRAIL sensitivity. A structure-activity relationship analysis reveals that the γ-butyrolactone ring of the dibenzylbutyrolactone lignans is essential for the rapidly reversible TRAIL-sensitizing activity of these compounds. Furthermore, the lignan nortrachelogenin (NTG) is identified as the most efficient of the 27 tested lignans and norlignans in sensitization of androgen-deprived prostate cancer cells to TRAIL-induced apoptosis. While this combinatorial anticancer approach may leave normal cells unharmed, several efficient cancer drugs are too toxic, insoluble or unstable to be used in systemic therapy. To enable use of such drugs and to protect normal cells from cytotoxic effects, cancer-targeted drug delivery vehicles of nanometer scale have recently been generated. The newly developed nanoparticle system that we tested in vitro for cancer cell targeting combines the efficient drug-loading capacity of mesoporous silica to the versatile particle surface functionalization of hyperbranched poly(ethylene imine), PEI. The mesoporous hybrid silica nanoparticles (MSNs) were functionalized with folic acid to promote targeted internalization by folate receptor overexpressing cancer cells. The presented results demonstrate that the developed carrier system can be employed in vitro for cancer selective delivery of adsorbed or covalently conjugated molecules and furthermore, for selective induction of apoptotic cell death in folate receptor expressing cancer cells. The tested carrier system displays potential for simultaneous delivery of several anticancer agents specifically to cancer cells also in vivo.

Luistonestojärjestelmän ja elektronisen tasauspyörästön suunnittelu ja implementointi hybridityökoneympäristöön

Ympäristörasituksen vähentäminen, tiukkenevat päästörajat ja ehtyvät öljyvarat ovat ajaneet kulkuvälineteollisuuden hakemaan uusia vaihtoehtoja ajoneuvojen energiatehokkuuden kehittämiseksi. Hybriditeknologia tarjoaa ratkaisuja kustannustehokkuuden ja ympäristöystävällisyyden parantamiseksi. Hybriditeknologian yleistyessä myös työkoneympäristössä saadaan paitsi kehitettyä energiatehokkaampia ja pienemmillä käyttökustannuksilla olevia työkoneita, niin myös tuotua siviiliajoneuvoista tuttuja turvallisuusominaisuuksia työkoneympäristöön. Perinteisten diesel-moottorien korvaaminen nopeavasteisilla ja tarkasti säädettävillä sähkömoottoreilla tarjoaa mahdollisuuksia toteuttaa tarkempia ja monipuolisempia säätöjärjestelmiä kuin perinteisessä ympäristössä. Tässä diplomityössä suunnitellaan luistonestojärjestelmä ja elektroninen tasauspyörästö hybridityökoneympäristöön. Järjestelmä voi käyttökohteesta riippuen pienentää huomattavasti käyttökustannuksia ja mahdollistaa uusien sovellusten tuomista markkinoille, kuten esimerkiksi kääntymisen avustaminen differentiaalisella ohjauksella.

Sähkömoottoriprototyypin mekaniikkasuunnittelu järjestelmällisen tuotesuunnittelun avulla

Työn tavoitteena oli suunnitella sähkömoottoriprototyyppi, joka soveltuu hybridiajoneuvon ajomoottoriksi. Mekaniikkasuunnittelu toteutettiin samanaikaisesti sähkösuunnittelun kanssa ja siinä käytettiin yleisesti käytössä olevaa järjestelmällistä tuotesuunnittelua. Järjestelmällinen tuotesuunnittelu soveltuu laajoihin suunnitteluprojekteihin, sillä sen avulla suunnitteluprosessi on jaoteltu useampiin pieniin askeliin. Työssä esitetään sähkömoottorin yleistä toimintaperiaatetta sekä niitä sähköteknisiä erityispiirteitä, joita mekaniikkasuunnittelussa tulee ottaa huomioon. Työn tuloksissa käytiin yksityiskohtaisesti läpi roottorin suunnittelu. Muille komponenteille käytettiin samaa järjestelmällistä tuotesuunnittelua mutta niitä ei esitetä yksityiskohtaisesti tässä työssä. Kokonaisuudessaan sähkömoottorista saatiin suunniteltua ratkaisuehdotus, joka täyttää halutut vaatimukset. Lisäksi työssä kerättiin kattava lista standardeista, jotka tukevat sähkömoottorin suunnittelua. Järjestelmällisen tuotesuunnittelun todettiin soveltuvan sähkömoottorin suunnitteluun hyvin ja saatua ratkaisuehdotusta voidaan pitää toimivana. Moottori suunnitelmasta valmistetaan ensimmäinen prototyyppi keväällä 2012. Prototyyppiä voidaan kehittää suunnittelemalla siitä paremmin sarjatuotantoon soveltuva malli esimerkiksi vähentämällä koneistettavien osien määrää ja korvaamalla ne valukappaleilla.

Luistonestojärjestelmän ja elektronisen tasauspyörästön testaus ja implementointi hybridityökoneympäristöön

Työssä toteutettiin C-kielellä luistonestojärjestelmä ja elektroninen tasauspyörästö Simulinkmallien pohjalta hybridityökoneeseen. Hybridityökoneen sähkökäytöt mahdollistavat tarkan vääntömomentin säädön, joka mahdollistaa työssä kuvatun kaltaisen järjestelmän toteuttamisen. Toteutettua järjestelmää simuloitiin MeVEA Oy:n ajoneuvomallinnukseen kehitetyssä simulaattorissa. Lisäksi järjestelmästä kehitettiin Visedo Oy:n sähkökäyttösimulaattoriin sopiva versio, jota testattiin Visedon sähkökäyttöjä simuloivan ohjelman kanssa. Simulointituloksien mukaan luistonesto estää vetäviä pyöriä luistamasta liukkaalla alustalla eikä toisaalta vähennä aiheetta kuljettajan asettamaa vääntömomenttia. Myös sähköinen tasauspyörästö toimi kuten oli suunniteltu. Työssä kehitetty luistonesto tarvitsee toimiakseen tiedon ajoneuvon kokonaismassasta, joten työssä kehitettiin myös tapa ajoneuvon massan estimoimiseksi ajoneuvon kiihdyttäessä. Massan estimointia testattiin pitävällä ja liukkaalla alustalla. Massan estimointi toimi simulaattoriympäristössä hyvällä tarkkuudella.

Hybrid warfare – just a twist of compound warfare? : views on warfare from the United States Armed Forces perspective

The wars the Western armies are involved with today are different from those that were fought in the end of 20th century. To explain this change, the Western military thinkers have come up with various different types of definitions of warfare over the last 30 years, each describing the tendencies involved in the conflicts of the time. The changing nature of conflicts surfaced a new term – hybrid warfare. The term was to describe and explain the multi-modality and complexity of modern day conflict. This thesis seeks the answer for the question: what is the development of thought behind hybrid warfare? In this thesis the Vietnam War (1965-1975) is used as an example of compound warfare focusing on the American involvement in the war. The Second Lebanon War (2006) serves as an example of hybrid warfare. Both case studies include an irregular opposing force, namely National Liberation Front in Vietnam War and Hezbollah in the Second Lebanon War. These two case studies are compared with the term full spectrum operations introduced in the current U.S. Department of Army Field Manual No. 3-0 Operations to see the differences and similarities of each term. The perspective of this thesis is the American point of view. This thesis concludes that hybrid warfare, compound warfare and full spectrum operations are very similar. The first two terms are included in the last one. Although hybrid warfare is not officially defined, it will most likely remain to be used in the discussion in the future, since hybrid wars and hybrid threats are officially accepted terms.

Energy storage in electric drive system

In recent years the environmental issues and the energy saving have become increasingly import in modern society where industry is the major emission factor and energy consumer. Generally, most of the total energy consumption is caused by electrical drives used in industrial applications and thus improving the performance of electrical drives give an opportunity to improve the energy efficiency. In this Master Thesis improving the energy efficiency in different electrical drives is clarified with different cases: regenerative braking in the electric grid or recovery of the braking energy into an energy storage. In addition, as an example, the energy consumption of an elevator is analyzed by measurements. From these measurement results it can be estimated how much the share of the standby energy consumption is from the total energy consumption and how much regenerative energy is available. The latter part of the thesis concentrates on determination of the properties of lithium iron phosphate battery with measurements.

Marketing Plan of Electric Vehicle Charging Solutions to USA

The purpose of the Thesis was to evaluate the business environment of electrical vehicle charging equipment (EVSE) in USA, find the key issues of entering the US EVSE markets and to form a marketing plan for possible market entry. The external market research analyzed the environment, customers, competitors and demand of EVSEs. In the internal analysis the focus was on resources and capabilities, offering, performance, business relations and US related issues. The research about the business environment was done using already available information from market studies and seminars. In external analysis there were also two semi-structured interviews from market experts used. The internal analysis was done mostly by interviews, but also company’s internal data sources were used. The interviews were semi-constructed and included eight interviewees from each part of EVSE value chain. The research findings were analyzed using SWOT analysis, which was converted to a so called TOWS matrix for extracting strategies. As a result of the Thesis, valuable information about the US markets and their requirements for EVSEs was gained. By matching the strengths of the case company and market requirements, customer segmentation and targeting were done and a marketing plan was constructed for the case company to help their management to evaluate the feasibility of possible market entry and investments to USA.

Investment recovery period in electric motor of higher efficiency in pumping for irrigation

In this study, it was adjusted a mathematical model to measure the effect of electric motor efficiency on pumping system costs for irrigation on the tariff structure of conventional electricity and green horo-seasonal , and also to calculate the recovery period of the invested capital in higher efficiency equipment. Then, it was applied to a center pivot irrigation system in two options of electric motor efficiency, 92,6% (standard line) and 94,3% (high efficiency line), and the acquisition cost of the first corresponded to 70% the of the second. The power of the electric motor was 100hp. The results showed that the model allowed us to evaluate if a high efficiency motor was economically viable compared to the standard motor in each tariff structure. The high efficiency motor was not viable in the two tariff structures. In the green horo-seasonal tariff, would only be viable if its efficiency was 4.46% higher than the standard motor. In the conventional tariff, it would only be viable if the efficiency overcame 2.71%.

Quality of papaya hybrid grown under different irrigation depths

Irrigation is a practice widely used in fruit production in the Brazilian Northeast region, including in the papaya crop in order to increase their productivity. For the purpose of knowing the productive potential of papaya hybrid irrigated, an experiment was carried out in order to evaluate the performance of a papaya hybrid under different irrigations depths. Four irrigation depths (50, 75, 100 and 125% of ETo) were tested and the reference evapotranspiration was calculated by the Penman-Monteith model. The hybrid papaya used was UENF/Caliman 01, which was planted in single rows, spaced 4 x 2m from each other, and irrigated by dripping. The experimental design in randomized blocks was used with six replications and three plants per plot. The following variables were evaluated: transversal diameter, longitudinal diameter, pulp thickness, external and internal appearances, soluble solids, titratable acidity, pulp pH and soluble solids/titratable acidity relation. The higher transversal and longitudinal diameters of the fruit were obtained applying an irrigation depth of about 108% of evapotranspiration. The UENF/Caliman 01 hybrid can be cultivated in the semiarid region of the State of Paraiba, Brazil, with replacement rate of 100% ETo, without compromising the quality of the fruits.

Initial development of two eucalyptus hybrid submitted to irrigation

The eucalyptus offers several advantages compared to other forestry species and, by using the irrigation can increase productivity and decrease production time. The objective of the present study was to evaluate two hybrid eucalyptus (Grancam and Urograndis), no irrigation, dripping and micro sprinkler irrigated at 90, 120, 150 and 180 days after transplanting (DAT). The experiment was conducted at the experimental irrigation area in the State University of Mato Grosso do Sul, in the municipality of Aquidauna - State of MS, Brazil. The experimental design was randomized blocks, split plot with four blocks and two replications within each block, and the plots were composed by irrigation treatments (dripping, micro sprinkler irrigate and dry) and the subplots the hybrids (Grancam and Urograndis).The total area of the experiment had 3 hectares, where each plot consisted of 1 ha. It was evaluated plant height, stem diameter and canopy, stem basal area, the relationship between height and stem diameter, the relationship between height and canopy diameter and stem volume. Data were subjected to analysis of variance and compared by Tukey test at 5% probability. Irrigation systems and dripping sprinkle provide greater plant height, stem diameter, canopy diameter, stem basal area and stem volume.