The ability to reprogram adult somatic cells into induced pluripotent stem (iPS) cells could provide a valuable implement for in vitro disease modeling and drug discovery. More importantly, they may potentially serve as an unlimited source of cells for regenerative medicine. However, most of the iPS cells have been generated by retroviral vectors, and therefore they carry the risk of viral integration into the host genome. This problem prevents their use for clinical applications and regenerative medicine. mRNA-mediated delivery of reprogramming factors is an alternative approach for cellular reprogramming. mRNA-based reprogramming offers the advantage of being completely free of genomic integration and is therefore highly suitable for clinical translation. However, there are some limitations which must be overcome so that mRNA can be widely used for successful cellular reprogramming. In the current thesis, the attempt was to generate stable mRNA-iPS cells through overcoming those limitations. Several human donor cells were transfected with mRNA encoding reprogramming factors and the generation of two stable mRNA-iPS cell lines was shown. The resultant mRNA-iPS colonies were assessed for pluripotency markers. Their pluripotency features were evaluated by the viral-iPS cells produced by conventional retroviral vectors. It was noticed that the generation of mRNA-iPS cells was largely affected by the parental cells from which they were derived. However, characterization and evaluation of the generated mRNA-iPS cells proved their pluripotency states comparable to the viral-iPS cells. On the other hand, the aging hallmarks of the iPS cells were assessed in the second part of this thesis. The potential aging signatures of the iPS cells should be conducted before their use in clinical applications. Currently, there are controversial data regarding the ability of reprogramming to fully rejuvenate an aged somatic cell and reverse agerelated changes such as shortened telomeres, dysfunctional mitochondria and DNA damage. Moreover, mixed findings have been published regarding whether the iPS cells are fully rejuvenated or they might retain some of the aging hallmarks from the cells which they were derived. This thesis studied these controversies through the investigation of three hallmarks of aging including telomere length, mitochondrial alteration and DNA damage. Telomere elongation was indicated in the iPS cells. Furthermore, mitochondrial morphology and function were improved into more immature features in iPS cell lines than their corresponding fibroblasts. Moreover, the iPS cell lines were shown to have less amount of DNA damage compared to their parental fibroblasts. In summary, it can be concluded that generation of mRNA-iPS cells is largely affected by the primary donor cells from which they are derived. Furthermore, it seems that reprogramming enables reversion of aging signatures to a more youthful state.

There is an increasing trend of Internet of Things (IoT) solutions, and more products are getting connected to the internet. It is therefore important to create a protected link to prevent malicious attacks. This report includes Transport Layer Security (TLS) to create a secure link for the Message Queuing Telemetry Transport (MQTT) protocol. This study investigates how TLS affects the performance of internal system in terms of Energy consumption and time delay. For a use case in the form of a wireless emergency stop for conveyor belt. In summary, this resulted in the fact that despite large calculation models within TLS, the protocol had a minimal impact on the overall system. This is due to the MQTT protocol which accounted for the major impact of the system. There are attacks that TLS does not provide direct protection against, among these is Denial of Service (DoS) Attacks. Furthermore this study examines other protectionsolutions such as An Intrusion prevention System (IPS). That was configured and showed promising results against DoS attacks. Where the study examines other protection solutions and the application of an Intrusion Prevention System (IPS) is configured and tested to protect against Denial of Service attacks with successful results. / Det finns en ökande trend av Internet of Things (IoT), vilket innebär att fler produkter blir anslutna till internet. Det är därför viktigt att skapa en skyddadlänk för att förhindra skadliga attacker. Denna rapport inkluderar Transport Layer Security (TLS) för att skapa en säker länk för Message Queuing Telemetry Transport (MQTT) protokollet. Denna studie undersöker hur TLS påverkar det interna systemets prestanda när det gäller energiförbrukning och tidsfördröjning. För ett användningsfall i form av ett trådlöst nödstopp för transportband. Sammanfattningsvis resulterade detta i att trots stora beräkningsmodeller inom TLS hade protokollet en minimal inverkan på det övergripande systemet. Detta beror på MQTT protokollet som stod för systemets stora inverkan. Det finns attacker som TLS inte ger direkt skydd mot, bland dessa är Denial of Service (DoS) Attacker. Dessutom undersöker denna studie andra skyddslösningar, till exempel ett intrångsförhindrande system (IPS) som sedarmera konfigurerades för användsningsfallet och visade lovande resultat mot DoS attacker.

La détection précoce de foyers de scolytes est une étape déterminante des opérations phytosanitaires qui doivent permettre de réduire l’impact indirect des tempêtes sur les forêts de conifères, en particulier l’impact du typographe sur les pessières. Cette détection doit idéalement être efficace, précise et économique. La présente thèse portait sur le typographe, Ips typographus, en pessière dans le massif vosgien. Elle visait à étudier et à comparer les performances en termes de précision (détection, localisation et inventaire), de coût et de rapidité de mise en œuvre de différentes méthodes de détection: la surveillance au sol, la détection aéroportée par un observateur embarqué (hélicoptère et ULM), et la télédétection (photographies aérienne infrarouge et imagerie satellitaire à haute et très haute résolution). Dans le chapitre « techniques de détection au sol », nous avons évalué plusieurs méthodes de suivi (par transects, le long des routes carrossables et chemins forestiers, des courbes de niveau, à partir des foyers antérieurs, le long de parcours conditionnels liés aux foyers observés). Leurs performances ont été estimées via des simulations sous SIG (système d’information géographique) et les trajets qui ont présenté les meilleurs résultats ont ensuite fait l’objet d’une validation sur le terrain. Il en ressort que ce sont les trajets le long des routes carrossables et chemins forestiers ainsi que les trajets conditionnels qui présentent les meilleurs rapports efficacité/rendement dans la détection des foyers de scolytes. Le choix d’une de ces méthodes dépendra de la taille minimum des foyers que l’on veut observer. Nous avons ensuite évalué, dans le chapitre « détection aéroportée », les performances de techniques d’observations de foyers réalisées par un observateur embarqué à bord d’un hélicoptère et d’un ULM. Une première étape a consisté à optimaliser toute une série de paramètres de vol pour les deux types d’appareils afin de permettre à l’observateur embarqué d’être dans les meilleures conditions d’observation. Ensuite, nous avons évalué la précision de détection en fonction de divers types de trajets en ULM et hélicoptère. D’après nos résultats, les observations recueillies à l’aide des deux sortes appareils n’ont pas permis de détecter de manière satisfaisante les foyers de scolytes quelque soit le type de trajet utilisé. Ces résultats sont sans-doute dus, en partie, à la faible expérience des observateurs embarqués mais également aux caractéristiques spatiales des foyers d’infestation qui ne facilitent pas leur détection par ce genre de méthode. Enfin, dans le chapitre « télédétection », nous avons évalué les performances qu’offrent (1) des séries temporelles d’images SPOT, (2) la photographie aérienne infrarouge et (3) des images Quickbird dans la détection de foyers de scolytes. Pour tous ces types d’images, nous avons estimé la précision d’une classification automatique des foyers d’infestation, réalisée à partir de leurs caractéristiques spectrales, texturales et environnementales, par rapport aux autres éléments présents sur l’image. Ces analyses ont mis en évidence qu’il est possible d’atteindre une précision de classification relativement bonne (>80%) des foyers d’infestation sur des photographies aériennes et sur des images satellites à très haute résolution spatiale (Quickbird) grâce à des techniques de segmentation et de classification par arbre de décision. Par contre, il ne nous a pas été possible de déterminer de façon satisfaisante la précision de classification des images SPOT (haute résolution spatiale). Les résultats détaillés de chacune de ces méthodes de détections sont développés dans les différents chapitres de cette thèse. La discussion générale met ceux-ci en relation en abordant leurs avantages et inconvénients respectifs, et aborde les perspectives découlant de nos résultats.

Embryonic stem cells (ESCs) are pluripotent cells derived from the early embryo and are able to differentiate into cells belonging to the three germ layers. They are a valuable tool in research and for clinical use, but their applications are limited by ethical and technical issues. In 2006 a breakthrough report described the generation of induced pluripotent stem cells (iPSCs). IPSCs are ESC-like cells generated from somatic cells by forcing the ectopic expression of specific transcription factors. This circumvents the ethical issues about the use of embryos in research and provides multiple opportunities to understand the mechanisms behind pluripotency. The aim of this project was to generate sheep iPSCs and characterise them. In order to learn the technique I initially repeated the original iPSC methodology: the putative mouse iPSCs I have generated display a morphology typical of ESCs, characterised by a high nuclear to cytoplasmic ratio, and form colonies with neat edges and smooth domes. These cells are positive to Nanog, a marker of pluripotency, and can give rise to cells belonging to the mesodermal and the ectodermal lineages when differentiated in vitro. Since the main aim of the thesis was the derivation of sheep pluripotent cells, once established the protocol in mouse, I then moved to the generation of ovine iPSC colonies. The cells I have generated have a morphology similar to that of mouse ESCs, express markers of pluripotency such as alkaline phosphatase and Nanog and can differentiate in vitro and in vivo into cells belonging to the three germ layers. Additionally, these ovine iPSCs can contribute to live born chimeric lambs, although at low level.

Transthyretin (TTR)-associated amyloidoses are diseases wherein wild-type or mutant TTR forms amyloid fibrils that infiltrate multiple organs. Wild-type TTR amyloidosis, ATTRwt, is a sporadic disease characterized by deposits that occur mainly in the heart. Alternatively, >100 TTR mutants cause inherited forms, ATTRm, frequently featuring cardiac amyloid deposits. The goals of this research were to create a cell-based model of ATTR amyloidosis, to define the mechanism of cardiac TTR-associated amyloid at the cellular level, and to study several agents that could interrupt the amyloid process. We hypothesized that TTR oligomers were cardiotoxic and played a role in the mechanism of ATTR amyloidosis, and that cytotoxicity could be inhibited by diflunisal, doxycycline, and Kiacta®. Focusing on TTR proteins associated with cardiac amyloidosis (wild-type, L55P, V30A, and V122), we developed a thermal denaturation method for creating TTR oligomers that allowed us to study the direct effect of oligomers on cells. Congo red and thioflavin T analyses confirmed that the oligomers were on pathway to amyloid fibril formation. We tested the effect of TTR oligomers on rat and human cardiac cells by measuring cell viability and stress response (through live protease activity and qPCR). TTR-L55P oligomers elicited a cytotoxic effect; fluorescent microscopy indicated cellular uptake of the oligomers and continued intra-cellular aggregation. Cytotoxicity was blocked when TTR was heated in the presence of doxycycline; the drug appeared to dissociate TTR aggregates or stabilize the monomeric forms. We also investigated retinol-binding protein (RBP), a natural binding partner of TTR. By immuno-histochemistry, RBP was demonstrated in ATTRwt and ATTRm `non-amyloid' transplant heart tissues, localized to areas containing amyloid or in the case of the transplant tissue, regions that appeared to display ischemic damage. Serum RBP levels were significantly different in ATTR vs. age-matched controls (p = 0.03), and in ATTRwt vs. ATTRm (p <0.0001) by ELISA. These data provide evidence that TTR oligomers are cardiotoxic, possibly due to cellular internalization and progressive intracellular aggregation. Furthermore, our results support the use of doxycycline as a therapeutic in ATTR to target these amyloidogenic oligomers, and suggest that RBP may have potential as a disease biomarker.

Indoor Positioning System (IPS) focuses on locating objects inside Buildings. Till date, GPS has helped us obtain accurate locations outdoors. These locations have helped us in many ways like navigating to a destination point, tracking people etc. Indoor Positioning System aims at navigating and tracking objects inside buildings. [1] IndoorAtlas is a technology that works on the theory of Indoor Positioning System. Book-Hunt is an Android mobile application which majorly makes use of IndoorAtlas therefore making use of the technique of indoor tracking. This Android mobile application is designed for Libraries. It is designed specifically for John M. Pfau Library, CSUSB, to help the students locate a book in the Library. When a student selects a book, a marker is pointed towards the book and also on the student’s current location. This application aims at saving time for student searching a particular book in the Library. Book- Hunt makes use of three tools Android Studio, Google Maps and IndoorAtlas

<p>Denna studie är genomförd på en bultsvetsstation med fyra bultsvetsrobotar från ABB som används i den dagliga produktionen i karossfabriken på Saab Automobile i Trollhättan. I dagsläget används off-lineprogrammerade robotprogram från IGRIP i flera robotceller på karossfabriken. IGRIP har under flera år används utan att man har någon metod för att utvärdera för hur kapaciteten i robotcellerna utnyttjas. Begränsningarna hos IGRIP är att det inte automatiskt kan beräkna och generera kollisionsfria banor vilket är mycket tidskrävande. Programmeringen av via-punkterna sker via manuell inmatning i programmet vilket medför att de inte utnyttjar maximal kapacitet i robotcellen. Dessa problem har lett till att Saab ville undersöka potentialen för att frigöra kapacitet i en robotcell med hjälp av en programvara under utveckling, IPS 2.0. Den nyare programvaran utvecklas av FCC och besitter optimerings- och balanseringsfunktioner samt genererar kollisions fria rörelsebanor för robotarna i robotcellen. En optimerad bana och en referensbana har skapats för att kunna utvärdera en procentuell förändring av tiden. Det visade sig att det finns stor potential att frigöra kapacitet i den undersökta cellen med hjälp av IPS 2.0.</p> / <p>This study has been performed on a stud weld station consisting of four stud weld robots from ABB which are used in the daily production at the body plant of Saab Automobile in Trollhättan. Currently, off-line programmed robot programs from IGRIP are used in several robot cells in the body plant. IGRIP has been used for several years without having any evaluation method for how the capacity has been used in the robot cells. The limitations of IGRIP are that it cannot automatically generate collision free paths, which is very time consuming. The input of the via-points is done manually by the programmer which results in less than maximum capacity in the robot cell. These problems have triggered Saab to investigate the potential for making capacity available by using a software under development, IPS 2.0. The software is developed by FCC and has optimization and balancing functions. It can also generate collision free paths for the robots in a robot cell. One optimized path and one reference path have been created in order to evaluate the time reduction in percent. It was shown that there was potential to free up capacity in the robot cell by using IPS 2.0.Date:</p>

The U.S. Navy has developed in their ships, and is continually improving, electric propulsion, ship service power, and electric loads. The latest topology under design is the integrated power system (IPS). The IPS entails the all electric ship concept with electric propulsion, direct current (DC) distribution, and modular technology. In the all electric ship concept, ship propulsion and ship service loads are powered by alternating current (AC) generation. For the IPS, power electronics conversion is to be utilized to convert alternating current (AC) generation to direct current (DC) distribution. As state-of-the-art power electronics, the Navy plans to use power electronic building blocks (PEBB) technology in its IPS. A U.S. naval shipboard power system is required to be a highly reconfigurable system to enhance its survivability and reliability. Reconfiguration is a change in the shipboard power system state for various reasons such as new topology, changing missions and emergencies. It was decided to study the behavior of a PEBB-based integrated shipboard power system during reconfiguration. Since no real time operation data was available, the problem was studied through the simulation of reconfiguration scenarios on a scaled-down computer model of an IPS in MATLAB. Reconfiguration scenarios were determined and staged, and an AC/DC power system stability assessment methodology was applied by decoupling the IPS test system around an intrazonal bus. The coupled system of the test IPS, consisted of two dynamic 4160 VAC generators, two rectifiers, two DC-DC converters between the rectifiers' output looped bus and the downstream intrazonal 775V busses, inverters, buck converters, AC loads and DC loads. There was modeling of excitation perturbations which introduced errors in the assessment of the stability requiring an approximation analysis. The study found that the DC bus of interest was stable for all nine reconfiguration scenarios staged, but it found that other busses were not stable for two of the scenarios. The study further found that lower stability margins occurred at lower frequencies of about 1Hz for stable scenarios. It concluded that there were tangible benefits to advancing the shipboard power system architecture to the IPS topology because of the good stability results.

Denna studie är genomförd på en bultsvetsstation med fyra bultsvetsrobotar från ABB som används i den dagliga produktionen i karossfabriken på Saab Automobile i Trollhättan. I dagsläget används off-lineprogrammerade robotprogram från IGRIP i flera robotceller på karossfabriken. IGRIP har under flera år används utan att man har någon metod för att utvärdera för hur kapaciteten i robotcellerna utnyttjas. Begränsningarna hos IGRIP är att det inte automatiskt kan beräkna och generera kollisionsfria banor vilket är mycket tidskrävande. Programmeringen av via-punkterna sker via manuell inmatning i programmet vilket medför att de inte utnyttjar maximal kapacitet i robotcellen. Dessa problem har lett till att Saab ville undersöka potentialen för att frigöra kapacitet i en robotcell med hjälp av en programvara under utveckling, IPS 2.0. Den nyare programvaran utvecklas av FCC och besitter optimerings- och balanseringsfunktioner samt genererar kollisions fria rörelsebanor för robotarna i robotcellen. En optimerad bana och en referensbana har skapats för att kunna utvärdera en procentuell förändring av tiden. Det visade sig att det finns stor potential att frigöra kapacitet i den undersökta cellen med hjälp av IPS 2.0. / This study has been performed on a stud weld station consisting of four stud weld robots from ABB which are used in the daily production at the body plant of Saab Automobile in Trollhättan. Currently, off-line programmed robot programs from IGRIP are used in several robot cells in the body plant. IGRIP has been used for several years without having any evaluation method for how the capacity has been used in the robot cells. The limitations of IGRIP are that it cannot automatically generate collision free paths, which is very time consuming. The input of the via-points is done manually by the programmer which results in less than maximum capacity in the robot cell. These problems have triggered Saab to investigate the potential for making capacity available by using a software under development, IPS 2.0. The software is developed by FCC and has optimization and balancing functions. It can also generate collision free paths for the robots in a robot cell. One optimized path and one reference path have been created in order to evaluate the time reduction in percent. It was shown that there was potential to free up capacity in the robot cell by using IPS 2.0.Date:

This thesis comprises an investigation in order to find possibilities to implement the method used in the automotive industry to automatically generate a collision free measurement program within the aircraft components manufacturer. The purpose with the study was to compare and analyse the different methods used to generate measurement programs at GKN Aerospace Engine Systems in Trollhättan, National Electric Vehicle Sweden (NEVS) and Volvo Cars Corporations (VCC).The study was conducted through meetings, observations and questionnaires with staff from the geometry assurance engineering (GAE) departments and measurement departments in each company. By mapping the virtual GAE process started from concept development in CAD to the measurement phase in which components are measured in coordinated measuring machines (CMM), a chain of activities was analysed.NEVS and VCC are today using RD&amp;T and IPS to generate optimized CMM programs in which a time efficient measurement path can be generated. This method was compared with the current approach at GKN Aerospace where they use one supplier for offline CMM programming (OLP) software solutions and CMMs. They are thereby working in a closed system where the OLP communicates with the CMM by supplier specific methods. The automobile manufacturer NEVS and VCC, in contrast, uses a DMIS protocol which is an ISO and ANSI standard.The study shows that an implementation of the software used by the Swedish automobile manufacture NEVS and VCC at GKN Aerospace in Trollhättan, may not have any significant improvements regarding time savings and thereby no economic benefits. However, the approach for generating an optimized measurement program in RD&amp;T and IPS may have major improvements in other facilities within the aerospace industry which has also resulted in an instruction manual to be used for potential implementation.