Phosphoinositide 3-kinase is a family of lipid kinases that function by phosphorylating the D3 position of phosphoinositide (PI) lipids generating PI(3)P, PI(3,4)P2 and PI(3,4,5)P3. These D3 phosphoinositides regulate various cellular processes through the recruitment of effector proteins containing lipid specific pleckstrin homology (PH) domains. PI phosphatases such as PTEN and SHIP function to restrain PI3K signaling by limiting the amount of D3 PI available for binding. Deletion of either PTEN or SHIP significantly alters B cell function and humoral immune responses. TAPP1 and TAPP2 are dual PH domain containing adaptors which selectively bind the phosphoinositide PI(3,4)P2 via their C-terminal PH domains. PI(3,4)P2 is a lipid messenger generated by PI3K and through the inositol phosphatase activity of SHIP. The function of PI(3,4)P2 remains incompletely understood. To identify the functional role of TAPP-PI(3,4)P2 interactions, we utilized a knock-in (KI) mouse bearing mutations within the PI-binding pocket of both TAPPs. Our study assessed the effect of PI3K dependent KI mutation on B lymphocyte development, activation and antibody production. Flow cytometry analyses of lymphoid tissues found that TAPP KI mice develop relatively normal frequencies of mature B cell populations with the exception of peritoneal B1 cells, which are increased by approximately 50%. Strikingly, TAPP KI mice developed substantially elevated serum antibody levels. TAPP KI mice were able to generate high affinity antigen-binding antibodies upon immunization with NP-OVA in alum adjuvant; however, total immunoglobulin production was markedly increased under this immunization condition. We further assessed the germinal centre (GC) response, which are known to require PI3K signaling and a hallmark of T cell dependent (TD) antibody responses. TAPP KI mice generated larger germinal centers (GC) upon immunization, which was associated with increased GC B cell survival. We further assessed whether uncoupling of TAPPs from PI(3,4)P2 alters B cell signaling and functional responses in vitro. B cells purified from TAPP KI mice were found to have altered functional responses in vitro, with significantly increased survival and cell division following antigen receptor cross-linking. Consistent with increased cell survival, TAPP KI B cells show increased Akt phosphorylation on Ser473 and Thr308 after antigen receptor cross-linking. However, reconstitution of B cell deficient mice with either WT or TAPP KI B cells was found to generate similar GC responses, suggesting that activation of other cells may contribute to the enhanced in vivo responses. Consistently, when we examined the CD4+ T follicular helper cells, a subset providing critical cues to GC responses, we found increased expression of ICOS activation marker. Our results indicate the interactions of TAPP adapters with PI(3,4)P2 serve to restrain lymphocyte activation and limit antibody production, providing the first in vivo evidence that this interaction is important for immune function.

In area of Smart-home control, there are requirements for miniaturisation, security and advanced control logic of individual member of system at present. One of the challenges is the way of data collecting from terminal nodes and data processing, including their distribution to the others nodes of Smart-home. The goal of this thesis is to design and to produce Smart-home control node, which will be a gateway between sensoric net and database and will be developed and produced on embedded system with speci c HW boards. Functionality of this gateway should include error states, e.g. should cache sensor messages when the connection between gateway and server interrupts, or take care about time synchronising. The thesis describes theoretical side of gateway design and also practical side of programming and producing SW for the gateway in Smart-home system.

Syfte: Syftet med det här examenarbete är att undersöka behovet av snabbkopplingsadaptrar för protesbrukare.   Bakgrund: Snabbkopplingsadapter är en förhållandevis ny produkt som både Otto Bock och Lindhe Xtend erbjuder, men ingen forskning på behovsområdet finns ännu gjord. Fördelen med produkten är enligt leverantörernas hemsidor bl a att man med den enkelt kan byta mellan olika proteskomponenter utan att behöva skruva på några protesinställningar eller byta hylsa.   Metod: För att undersöka behovet av snabbkopplingsadaptrar utfördes semistrukturella intervjuer av fenomenologisk karaktär. En serie med sju frågor sammanställdes som intervjuunderlag, vilka togs fram utifrån de tre behovsfokusområdena: Funktion, delaktighet och livskvalité. I undersökningen ingick n=6 deltagare, varav n=3 transtibialt amputerade och n=3 transfemoralt amputerade. Insamlade data analyserades vidare för framtagning av olika teman och resultat.   Resultat: Utifrån intervjuunderlaget togs följande teman fram: Byte av protesfötter/protesknäleder, På- och avtagning av byxor, Hylspassform, Transport samt Biomekanik. Varje tema utgjorde ett eget potentiellt användningsområde, där de största behoven visade sig ligga inom temana Byte av protesfötter/protesknäleder, Hylspassform samt Transport.   Slutsats: Behovet av snabbkopplingsadaptrar är högst subjektivt, och beror snarare på deltagarens liv än några allmänna faktorer. Däremot upptäcktes ett antal tänkbara användningsområden för den. / Aim: The aim of this thesis was to investigate the necessity of the quick change adapter for lower limb amputees.   Background: Quick Change Adapter is a relatively new product that both Otto Bock and Lindhe Xtend offers, but no research has been done on the area of its necessity yet.  According to the supplier´s websites the benefits of the product is that you with it easily can change prosthetic components without affecting the alignments or change socket.   Method: To investigate the necessity of the Quick Change Adapter, semi structural interviews of phenomenological characteristic were used.  A series of seven questions were compiled as a basis for the interview from the three focus areas: Function, participation and quality of Life. The thesis involved n=6 participants, of who n=3 was trantibial amputated and n=3 transfemoral amputated. Collected data was later analysed to find general themes and results.   Results: From the interviews these themes were exposed: Changing prosthetic feet/prosthetic knee joints, Donn and doff of pants, Socket fit, Transport and Biomechanics. Each theme presented a potential application area where the biggest needs seemed to be in Changing prosthetic feet/prosthetic knee joints, Socket fit and Transport.   Conclusions: The necessity of the Quick Change Adapter turned out to be very subjective, and depended more on the participant´s life then any general factors. Still there were some potential application areas detected for it.

Yes / A confocal microscope provides a sequence of images, at incremental depths, of the various corneal layers and structures. From these, medical practioners can extract clinical information on the state of health of the patient's cornea. In this work we are addressing problems associated with capturing and processing these images including blurring, non-uniform illumination and noise, as well as the displacement of images laterally and in the anterior posterior direction caused by subject movement. The latter may cause some of the captured images to be out of sequence in terms of depth. In this paper we introduce automated algorithms for classification, reordering, registration and segmentation to solve these problems. The successful implementation of these algorithms could open the door for another interesting development, which is the 3D modelling of these sequences.

Nowadays, static analysis is a helpful option for developers to ensure all the important properties of a developed application. But these analyses must be also developed and it is inevitable that sometimes they must be debugged to find and solve problems inside of the analyses themself. The debugging of static analyses might be more complicated because some popular analysis frameworks do not provide sufficient support for debugging. One of the widely used analysis frameworks is WALA. In this thesis, we thoroughly explored all the main features of WALA and determined possible points for better debugging support. For each of these points, we designed and implemented supporting infrastructure that should accelerate the process of debugging by avoiding the tedious manual effort needed for inspection and evaluation of the internal state of WALA. One kind of these points is the analysis configuration where we created an inspection system for class hierarchy and call graph that should detect common misconfiguration problems. The next point is the debugging of the data flow transfer functions, for which we created a visualizer of the running analysis over the subject program. This visualization is done within the Visual Studio Code editor. To connect the editor with the analysis we used Debug Adapter Protocol and...

Den här rapporten beskriver ett examensarbete i elektroteknik på Kungliga tekniska högskolan. Syftet var att skapa en unik systemlösning där ett CAN-adapterkort (Controller Area Network) skulle integreras med ett system för övervakning av däcktryck i tunga fordon. Målet var att presentera mätvärden från ventilsensorer på en persondator. Systemet för övervakning av lufttryck heter J1939 – TPMS och är en färdig produkt. J1939 – TPMS skickar CAN-ramar på en CAN-buss i J1939-format. Dessa ramar ska läsas in av adapterkortet och presenteras på ett terminalprogram på en persondator. Arbetet har bestått av att utreda hur systemet J1939 – TPMS fungerar i detalj. Rollen för protokollet J1939 och dess förhållande till CAN har förklarats. Hur J1939-ramar tolkas och hur mätdata rörande TPMS avkodas har beskrivits i detalj. Principer för hur en CAN-nod fungerar har klargjorts. Baserat på detta har ett CAN-adapterkort konstruerats. Konstruktionen har inneburit komponentval, design av elektronikschema, design av mönsterkort och utveckling av inbyggd programvara. Resultatet blev ett färdigt och fungerande CAN-adapterkort som har testats med J1939 – TPMS. Kraven för projektet uppfylldes. Dock så kommer mer arbete med kortet och systemet behövas för att det ska bli en färdig produkt. Arbetet genomfördes hos Motion Control i Västerås AB i samarbete med Transeco Däckservice. / This report describes a degree project at the Royal Institute of Technology. The purpose was to create a unique system solution in which a CAN adapter card (Controller Area Network) was to be integrated with an air pressure monitoring system for heavy duty vehicles. The goal was to present measurement values ​​from valve sensors on a personal computer. The air pressure monitoring system is called J1939 - TPMS and is a finished product. J1939 - TPMS sends CAN-frames to a CAN-bus in J1939 format. These frames are to be read by the adapter card and presented on a terminal program on a personal computer. The job has been to investigate how the J1939 - TPMS system works in detail. The role of the J1939 protocol and its relationship with CAN has been clarified. Also, a detailed description of how J1939 frames are interpreted and how the measuring data TPMS is decoded is done. Principles for how a CAN node works has been clarified. Based on this, a CAN adapter card has been designed. The design has included component selection, design of electronics schema, design of computer cards and development of embedded software. The result was a ready-to-use CAN adapter card tested with J1939-TPMS. Requirements for the project were met. However, more work with the card will be needed to make it a finished product. The work was carried out at Motion Control in Västerås AB in cooperation with Transeco Däckservice (Transeco Tire Service).

Wir betrachten offene Systeme; Systeme mit Schnittstelle und Verhalten in Form eines Protokolls. Offener Systeme interagieren durch den Austausch von Nachrichten. Die Interaktion ist korrekt, wenn die interagierende offenen Systeme terminieren können. Die korrekte Interaktion unabhängig entwickelter, offener Systeme ist nicht immer möglich. Obwohl ein offenes Systeme Funktionalität bereitstellt, die ein zweites offenes System benötigt, können Inkompatibilitäten in den Schnittstellen oder im Verhalten dazu führen, dass Nachrichten nicht korrekt ausgetauscht werden. Hier kommt die Idee eines Adapters zum Tragen, der solche Unterschiede ausgleicht. Wir führen eine Technik ein, die Inkompatibilitäten der Schnittstelle und des Verhaltens getrennt voneinander betrachtet. Mit Hilfe von Transformationsregeln geben wir an, wie Nachrichten zweier offener Systeme im Zusammenhang stehen. Wir modellieren so korrekten Datenfluss zwischen den Schnittstellen der offenen Systeme. Mit Hilfe existierender Techniken zur Controllersynthese erzeugen wir korrekten Kontrollfluss, sodass die Transformationsregeln so angewendet werden, dass Inkompatibilitäten im Verhalten überwunden werden. Wir erzeugen korrekten Kontrollfluss. Die Einheit aus Transformationsregeln und Controller bezeichnen wir als Adapter. Aufbauend auf dieser Technik betrachten wir in dieser Arbeit folgende Fragestellungen: - Welche Eigenschaften besitzt die vorgestellte Technik? Wann existiert ein Adapter? Wie lässt sich die Technik allgemein auf offene, kommunizierende Systeme anwenden? - Wie verteilen wir einen generierten Adapter auf verschiedene Komponenten? - Welche Informationen können wir bereitstellen, falls wir keinen Adapter finden? - Wie leiten wir ein formales Modell eines Adapters ab, wenn wir nur aufgezeichnetes Verhalten der offenen Systeme, aber keine formalen Modelle gegeben haben? / We consider open systems being described by an interface and behavior in form of an protocol. Interaction between open systems means exchange of messages. For the interaction to be correct, the interacting open systems must be able to terminate. The interaction of independently developed open systems is not guaranteed to be correct. Although one open system provides functionality a second open system requires, incompatiblities of the interfaces or the behavior may prevent the correct exchange of messages. The idea is to introduce an adapter to overcome the incompatiblities. We present a technique that considers incompatiblities of the interfaces and the behavior separately. With transformation rules we specify how messages of two open systems relate to each other. Using these rules we model the data flow between open systems and overcome incompatiblities of the interfaces. By using existing techniques for controller synthesis we overcome incompatiblities of the behavior. Thus we create correct control flow. We call the composition of transformation rules and controller an adapter. Based on the technique presented in this thesis, we want to answer the following reseach questions: - What are the properties of the proposed technique? When does an adapter exist? How can we apply the technique on open, communicating systems in general? - How do we distribute a generated adapter to different components? - Which information can we provide, if adapter synthesis fails? - How can we discover a formal model of an adapter, when we only have recorded behavior of open systems, but no formal models?

A cardiomiopatia chagásica crônica é a consequência mais grave da Doença de Chagas, quadro infeccioso humano causado pelo protozoário Trypanosoma cruzi. Uma vez que os cardiomiocitos podem ser invadidos pelo T. cruzi, é nosso interesse averiguar se esta população estrutural reconhece o parasita in vivo através dos TLRs (Toll Like receptors). Visto que a maioria dos TLRs sinaliza através da molécula adaptadora MyD88, no presente trabalho temos estudado a participação deste elemento transdutor. Para isto fomos examinar a infecção pelo T. cruzi em camundongos F2 (Mer / MyD88flox+/+), modelo animal no qual o tratamento com a droga Tamoxifeno deve eliminar a molécula MyD88 exclusivamente nos cardiomiócitos. Resultados: em um estudo prévio, constatamos que cardiomiócitos tumorais murinos HL-1, em repouso ou após infecção pelo T. cruzi, transcrevem a molécula MyD88. A seguir, validamos o modelo experimental in vivo, ao mostrar que o tratamento com tamoxifeno dos animais F2 resulta na diminuição de MyD88 no coração, mas não no baço. Ainda, constatamos que a transcrição de MyD88 é mais intensa na aurícula do que no ventrículo, sendo igualmente abolida dos animais F2 pelo tratamento com tamoxifeno. Por outro lado, verificamos que o tamoxifeno determina um aumento da parasitemia em ambos os animais F2 e controle (MerCreMer+/+), não se observando diferenças significativamente entre estes. Finalmente, estudos preliminares mostraram que a eliminação de MyD88 nos cardiomiócitos dos animais F2 não altera significativamente o quadro de patologia (parasitismo e infiltração leucocitária) aos 10 ou 28 dias de infecção pelo T. cruzi, quando comparado ao de animais controle (MerCreMer+/+) igualmente tratados com tamoxifeno e infectados. / Chronic Chagas cardiomyopathy is the most serious consequence of Chagas Disease, caused by Trypanosoma cruzi. Cardiomyocytes are invaded by T. cruzi, it is our interest to see if this structural population in vivo recognizes the parasite through TLRs. Since most TLRs signal through MyD88, we studied in vivo participation of Myd88 in cardiomyocyte response. Treatment with tamoxifen (Tam) eliminate the MyD88 molecule exclusively from cardiomyocytes in F2 mice, which we used to understand its role on T. cruzi infection. Results: HL-1 cells, a murine cardiomyocyte tumor line, in infection with T. cruzi, transcribe the MyD88 molecule. Transcription of MyD88 is more intense in the atria than in ventricle. Tam treatment of F2 mice eliminates the MyD88 at the heart completely, but not at spleen. Tam caused increased parasitaemia, no differences were observed in the parasitaemia curve of infected F2 and MerCreMer+/+ (control) mice. Finally, MyD88 elimination in cardiomyocytes of F2 mice does not alters the pathology frame at days 10 and 28 post infection.

<p>Media extenders or digital media receivers are network devices that are used to retrieve digital media files (such as music, pictures, or video) from a media server and play or show them on a TV or home theater system. A technology that is often associated with these devices is the Universal Plug and Play (UPnP) technology. This technology enables network devices to be used without requiring the user to do network configuration on it. This thesis demonstrates how a device that is normally used for receiving digital television broadcasts can be enhanced to support media extender functionality. The thesis describes the design and implementation of the technologies that are needed to accomplish this functionality. The main topics are centered around on how UPnP awareness and media rendering (decoding) are incorporated into the device.</p>

Manufacturing today has become a matter of the effective and efficient application of information technology and knowledge engineering. Manufacturing firms success depends to a great extent on information technology, which emphasizes the integration of the information systems used by a manufacturing enterprise. This integration is also called enterprise application integration (here the term application means information systems or software systems). The methodology for enterprise application integration, in particular enterprise application integration automation, has been studied for at least a decade; however, no satisfactory solution has been found. Enterprise application integration is becoming even more difficult due to the explosive growth of various information systems as a result of ever increasing competition in the software market. This thesis aims to provide a novel solution to enterprise application integration. The semantic data model concept that evolved in database technology is revisited and applied to enterprise application integration. This has led to two novel ideas developed in this thesis. First, an ontology of an enterprise with five levels (following the data abstraction: generalization/specialization) is proposed and represented using unified modeling language. Second, both the ontology for the enterprise functions and the ontology for the enterprise applications are modeled to allow automatic processing of information back and forth between these two domains. The approach with these novel ideas is called the enterprise semantic model approach. The thesis presents a detailed description of the enterprise semantic model approach, including the fundamental rationale behind the enterprise semantic model, the ontology of enterprises with levels, and a systematic way towards the construction of a particular enterprise semantic model for a company. A case study is provided to illustrate how the approach works and to show the high potential of solving the existing problems within enterprise application integration.