Les cèl.lules "natural killer" (CNK) van ser descobertes a l'inici de la dècada de 1970 per la seva capacitat de lisar de forma espontània cèl.lules tumorals. Estudis realitzats posteriorment han posat de manifest que aquesta població cel.lular està continguda en els limfòcits grans granulats (LGG) de sang perifèrica (SP) i que poseeixen unes estructures de membrana característiques definides pel CD16 i CD56.La funció de les CNK dintre de l'organisme és molt àmplia. Controla el creixement i disseminació de cèl.lules tumorals i de cèl.lules infectades pel virus, regula el creixement de la "stem cell" hemopoètica, participa en el rebuig d'empelts i produeix diverses citoquines que controlen la funció dels limfòcits B i T. La leucèmia limfàtica crònica de línia B (LLC-B) és el procés limfoproliferatiu més freqüent en el nostre ambient. Dintre de l'espectre de signes i símptomes de la malaltia s'han descrit diverses alteracions immunes que afecten tant als limfòcits B com els limfócits T. En els últims anys diversos autors han suggerit que la CNK present en pacients amb LLC-B presenta alteracions. Els treballs realitzats sobre la CNK a la LLC-B són pocs i inclouen un nombre petit de malalts. El motiu que provoca el defecte funcional trobat en la població "natural killer" (NK) no es coneix. A més, cap d'aquests treballs analitza l'activitat "natural Killer" (ANK) en relació amb les característiques clínico-analítiques dels pacients. Per aquestes raons, els principals objectius de la recerca presentada en la present tesi són els següents:1. Mesurar l'ANK en pacients amb LLC-B2. Relacionar l'ANK amb les característiques dels pacients.3. Valorar l'efecte del tractament sobre l'ANK dels pacients amb especial atenció a l'efecte de l'interferó "in vivo". / Natural killer (NK) cells play a role in immune surveillance against tumoral and infected cells, and display immunoregulatory functions over B and T lymphocytes. In B cell chronic lymphocytic leukemia (B-CLL) there exist immune alterations affecting B and T lymphocytes. Recently NK disfunction was also noticed regarding activity (NKa) and surface phenotype. NKa was analyzed in 67 patients with B-CLL using the (51)Cr release assay and the lymphocytic phenotype by means of CD2, CD4, CD8, CD16, CD11b, CXD57, CND56 and CD19.

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This diploma thesis is focused on the LLC resonant power supply with power factor correction. The first part of the thesis is focused on a selection of a suitable controller for the control of this source. Here the emphasis is mainly on efficiency and EMC. The thesis also deals with the design of the scheme and the selection of suitable components. The thesis contains the design of the LLC power supply itself and also the power factor correction circuit - PFC.

The aim of this diploma thesis is to study the resonant converters operation. This paper is concretely specialized to design and implementation the LLC resonant converter with output power about 350 watts. LLC resonant converter is prospective solution for similar applications. The general advantages are that the power MOSFETs are working on zero voltage switching condition, which reduce the switching loss and improve EMI performance. The detailed design for the LLC resonant tank characteristics presented in this paper, which fully guarantees the ZVS condition. This study is based on replacing the rectifier and load by an equivalent resistance applies the first harmonics approximation and the assumption that the current trough the diodes of the output rectifier has a sinusoidal waveform.

The project deals with the design of a switch-mode power supply (SMPS) with a medium and high power output. The power supply uses multiphase control switching. Electric energy is converted through a series parallel LLC resonant circuit to reach the maximum efficiency with a small size and cost efficiency of the designed power supply. The semiconductor switches use ZVS (Zero Voltage Switching) on the primary side and ZCS (Zero Current Switching) on the secondary side of the converter. The design of the converter is based on the knowledge of the high power output converters (types of switching, art topologies) and resonant topologies (series resonant circuit – SRC, parallel resonant circuit – PRC and series parallel circuit –SPRC). The design of the converter was done theoreticaly and tested by using simulation program. The simulation and partial tests served to build prototype the Interleaves Converter (ILLC). The function of the converter was tested in laboratory. The laboratory results have been compared with the theoretical and the simulation results.

La leucémie lymphoïde chronique (LLC) est une hémopathie maligne caractérisée par l’accumulation, dans le sang et les organes lymphoïdes secondaires, de lymphocytes B matures résistants à l’apoptose. Le microenvironnement tumoral de la LLC au sein des organes lymphoïdes secondaires, et notamment les « Nurse-Like Cells » (NLCs), joue un rôle majeur dans la promotion de la survie et de la prolifération des cellules leucémiques. Au cours de cette étude, la surexpression du récepteur de la neurotensine NTSR2, un récepteur couplé aux protéines G, a été caractérisée. Il est activé de façon constitutive dans les cellules leucémiques circulantes, et son activation dépend de son interaction avec le récepteur à activité tyrosine kinase TrkB suite à la liaison de son ligand, le BDNF, tous deux également surexprimés. L’activation de NTSR2-TrkB par le BDNF entraine une signalisation de survie par les voies Src et Akt, aboutissant à la surexpression des protéines anti-apoptotiques Bcl-2 et Bcl-XL. L’inhibition du récepteur NTSR2 dans ces cellules fait diminuer leur viabilité. En présence des NLCs, les expressions de NTSR2, TrkB, BDNF, et de la sortiline, protéine de transport des neurotrophines et des récepteurs Trk, est accentuée. Les NLCs produisent elle-même du BDNF, activent la voie de signalisation Src, et leur rôle protecteur des cellules leucémiques est BDNF-dépendant. L’ensemble de ces travaux met en évidence un rôle capital de NTSR2-TrkB-BDNF dans la signalisation de survie des cellules leucémiques circulantes et au sein du microenvironnement tumoral de la LLC, et pourrait ainsi constituer une nouvelle cible thérapeutique potentielle. / Chronic lymphocytic leukemia (CLL) is a malignant hemopathy characterized by the accumulation of apoptosis resistant mature B lymphocytes in peripheral blood and secondary lymphoid organs. In these secondary lymphoid organs, the tumor microenvironment, notably Nurse-like Cells (NLCs), plays a major role in leukemic cells survival and proliferation promotion. In this study, an overexpression of neurotensin receptor NTSR2, a G-protein coupled receptor, was identified. NTSR2 is constitutively activated in circulating leukemic cells and its activation depends on its interaction with tyrosine kinase activity receptor TrkB upon binding of its ligand, BDNF. Activation of NTSR2-TrkB by BDNF induces survival signaling by Src and Akt pathways, and in term anti-apoptotic proteins Bcl-2 and Bcl-XL overexpression. Inhibition of NTSR2 in those cells impacts their viability. In the presence of NLCs, expressions of NTSR2, TrkB, BDNF, and sortilin, a neurotrophin and Trk receptor transport regulator, are enhanced. NLCs produce BDNF, stimulate Src activation, and their protective role on leukemic cells is BDNF-dependent. Taken together, this study highlights a key role of NTSR2-TrkB-BDNF in leukemic cells survival signaling, both in the circulation or in the tumor microenvironment, and might thus constitute a potential new therapeutic target.

No description available.

In today's industrial power converters, converter reliability is essential, and converter topologies are well-established. Without a doubt, the power electronic industry continues to seek efficient power delivery and high power density. Resonant converters, especially LLC converters, have been intensively studied and applied in DC-DC converters. One of the most demanding applications for LLC converters is data centers. To date, LLC Resonant converters, are deployed in many applications for improved efficiency, density, and reliability. With the introduction of WBG devices coupled with the soft switching feature, the switching frequency can be extended beyond Mega-Hertz. With the significant increase in operating frequency, complicated magnetic components can be broken down into a cellular structure, each with a few number of turns. They can be easily implemented using 4-6 layers of PCB windings. Moreover, integrating the cellular cores using flux cancellation can further improve the power density. The proposed integrated magnetics can be automated in the manufacturing process. The magnetic size is reduced at this frequency, and planar magnetics using PCB winding become more relevant. PCB magnetics feature multiple advantages over Litz wire. The benefits are summarized as follows: The labor-intensive manufacturing process can be automated, thus reduction of cost. There is much reduced CM noise by using the shield layer. They have parasitics with much-improved reproducibility in large quantities. PCB windings feature less leakage between transformer windings because of the flexibility of the winding interleaving and the reduced number of turns. There is better thermal management due to the increased surface-to-body ratio. The design has a low profile and high-power density. However, it is not without its own limitations. There are challenges for high frequency PCB-magnetic magnetic design for the LLC converter. Firstly, With the recently developed high frequency core material, a phenomenon referred to as the dimensional resonant is observed. The effects of dimensional resonance were discussed in the literature when using an unusually large core structure; however, it can be observed more frequently under high excitation frequency, particularly with integrated magnetics. This dissertation discusses the dimensional effects of core loss on a PCB-based magnetics structure. A case study is presented on a 3-kW 400-to-48-V LLC prototype running at 1 MHz. The converter utilizes a low-profile matrix of two integrated transformers with a rectangular and thin cross-section area for reduced core loss. Specific solutions are presented. % Secondly, The matrix transformer is suitable for an LLC converter with high output current. However, the matrix transformer also increases the core size and core losses. The core loss degrades the LLC converter's light load and peak efficiency. In this dissertation, We discuss the design process and implementation of the DC-DC stage of the power supply unit for narrow range 48 V data center bus architecture. The optimization takes into account the number of elemental transformers, number of transformer turns, switching frequency, and transformer dimensions, namely winding width and core cross-section area. The optimization process results in a nearly 99% efficient 400-to-48-V LLC with a very high-power density and low profile fully integrated on PCB. A matrix of four transformers is used to reduce the termination loss of the secondary synchronous rectifier and achieve better thermal management. The number of secondary turns is optimized to achieve the best trade-off between winding loss, core loss, and power density. Another challenge arises for magnetic integration when multiple magnetic components with different characteristics come together. For instance, in the case of a transformer and an inductor on the same PCB. The PCB transformer is designed with perfectly interleaved primary and secondary layers to utilize the full PCB layer thickness. As a rule of thumb, the transformer winding layer is designed within 1 to 2 times the skin depth. On the other hand, the inductor's winding lacks interleaving and suffers from high MMF stress on layers. This makes the inductor prone to high eddy currents and eddy loss. Furthermore, this dissertation addresses the challenges associated with the high winding and core loss in the Integrated Transformer-Inductor (ITL). To overcome these challenges, we propose an improved winding design of the ITL by utilizing idle shielding layers for inductor integration within the matrix transformer. This method offers full printed circuit board (PCB) utilization, where all layers are consumed as winding, resulting in a significant reduction in the winding loss of the ITL. Moreover, we propose an improved core structure of the ITL that offers better flux distribution of the leakage flux within the magnetic core. This method reduces the core loss by more than 50% compared to the conventional core structure. We demonstrate the effectiveness of our proposed concepts by presenting the design of the ITL used in a high-efficiency, high-power-density 3-kW 400-to-48-V LLC module. The proposed converter achieves a peak efficiency of 98.7% and a power density of 1500 W/in3. This dissertation presents the concept of matrix inductors to solve such problems. A matrix of four resonant inductors is also designed to reduce the proximity effect between inductor windings and reduce inductor PCB winding loss. The matrix inductor provides a solution for high thermal stress in PCB-based inductors and reduces the inter-winding capacitance between inductor layers. This dissertation solves the challenges in magnetic design in high-frequency DC-DC converters in offline power supplies and data centers. This includes the transformer and inductor of the LLC converter. With the academic contribution in this dissertation, Wide-bandgap devices WBG can be successfully utilized in high-frequency DC-DC converters with Mega-Hertz switching frequency to achieve high efficiency, high power density, and automated manufacturing. The cost will be reduced, and the performance will be improved significantly. / Doctor of Philosophy / Industrial power converters need to be reliable and efficient to meet the power industry's demand for efficient power delivery and high power density. Research should focus on improving existing converter designs to improve fabrication, efficiency, and reliability. Resonant converters have been found to be effective in power conversion, especially in data centers where energy consumption is high. Three-element Resonant converters (LLC) are already used to improve efficiency, density, and reliability. By using Wide Bandgap devices and soft switching, the switching frequency can be extended beyond MHz, simplifying magnetic components and improving power density. The proposed integrated magnetics can be automated during the manufacturing process, further improving power density. At higher frequencies, planar magnetic components made with PCB winding are more effective than Litz wire. They are cheaper to make because of automation, have less common-mode noise, and are more reproducible in large quantities. PCB winding also has a low profile, high-power density, and better thermal management. However, it is not without its own limitations. There are challenges for high frequency PCB-magnetic magnetic design for the LLC converter. Firstly, With the recently developed high frequency core material, a phenomenon referred to as the dimensional resonant is observed. The effects of dimensional resonance were discussed in the literature when using an unusually large core structure; however, it can be observed more frequently under high excitation frequency, particularly with integrated magnetics. This dissertation discusses the effects of core loss on a PCB-based magnetics structure and presents solutions, including a case study on a 3-kW 400-to-48 V LLC prototype running at 1 MHz. Another challenge arises for magnetic integration when multiple magnetic components with different characteristics come together. For instance, in the case of a transformer and an inductor on the same PCB. The PCB transformer is designed with perfectly interleaved winding and low Ohmic loss. On the other hand, the inductor's winding lacks interleaving and suffers from a high proximity field. This makes the inductor prone to high eddy currents and eddy loss. This dissertation presents the concept of matrix inductors to solve such problems. A matrix of four resonant inductors is also designed to reduce the proximity effect between inductor windings and reduce inductor PCB winding loss. The matrix inductor provides a solution for high thermal stress in PCB-based inductors and reduces the inter-winding capacitance between inductor layers. Furthermore, this dissertation addresses the challenges associated with the high winding and core loss in the Integrated Transformer-Inductor (ITL). To overcome these challenges, we propose an improved winding design of the ITL by utilizing idle shielding layers for inductor integration within the matrix transformer. This method offers full printed circuit board (PCB) utilization, where all layers are consumed as winding, resulting in a significant reduction in the winding loss of the ITL. Moreover, we propose an improved core structure of the ITL that reduces the core loss by more than 50% compared to the conventional core structure. We demonstrate the effectiveness of our proposed concepts on a high-efficiency, high-power-density 3-kW 400-to-48-V LLC module. The proposed converter achieves a peak efficiency of 98.7% and a power density of 1500 W/in3. This dissertation solves the challenges in magnetic design in high-frequency DC-DC converters in offline power supplies and data centers. This includes the transformer and inductor of the LLC converter. With the academic contribution in this dissertation, Wide-bandgap devices WBG can be successfully utilized in high-frequency DC-DC converters with Mega-Hertz switching frequency to achieve high efficiency, high power density, and automated manufacturing. The cost will be reduced, and the performance will be improved significantly.

No description available.

Isolated inverters feature the freedom in voltage step-up/down, electrical safety, and modularity. Among them, pseudo-dc-link inverters have the advantage of high efficiency due to their single-stage structure. Traditionally, pseudo-dc-link inverters are based on pulse-width-modulated converters, which suffer from hard switching, the need for auxiliary components, and/or high current stresses. Meanwhile, the series resonant converter has been prevalent in past decades due to its simplicity and high efficiency. Therefore, it is intriguing to design a single-stage inverter based on a series resonant converter. However, there are limited papers regarding such an inverter topology. To figure out the reason, basic modulation methods proposed or implied in the literature are summarized and evaluated through circuit simulation software. It turns out each basic modulation method has at least one critical drawback in modulation range, hard switching, and/or high current stresses. Given the deficiencies in the basic modulation methods, a hybrid modulation method is proposed here. The proposed method combines variable-frequency modulation in the high-output region and short pulse-density modulation in the low-output region. In this way, all the aforementioned critical drawbacks can be greatly alleviated. The hybrid modulation method is compared to the basic modulation methods based on three design metrics: the rms value of the resonant current, the magnetic flux of the transformer, and the turn-off current. By these design metrics that directly related to power losses, the benefit of the proposed method in terms of efficiency can be explained. Moreover, a power loss model is also established to provide more insights into the inverter's efficiency performance. It helps demonstrate how the selection of resonant tank and other factors affects the power loss distribution. Also, an inverter design procedure is introduced and a prototype is built to verify the proposed modulation method. The results show that the switching losses, especially the turn-on loss, can be well suppressed, and the losses in other passive components are well restrained. This implies the proposed method is suitable for high-frequency applications. Other than efficiency, output waveform quality is also important for an inverter. However, the changing plant model makes the controller design difficult. Therefore, a third-order model established by other researchers has been adopted to identify the pole locations. In addition, a gain-varying method is proposed for the compensator to reduce the gain variance caused by different operating conditions. The experimental results show that without the gain-varying method, the inverter may have issues in slow tracking and/or instability. Finally, in some scenarios, the inverter based on a series resonant converter can be regarded as a module. A multi-modular inverter can be formed by connecting the modules in an input-parallel-output-series configuration. In this case, a technique termed sequential waveform synthesis can be applied. The proposed technique can extend the region of variable-frequency modulation and shorten the region of short pulse-density modulation. This is beneficial to efficiency based on an analysis. With more than a certain amount of modules connected, the short pulse-density modulation can even be waived, which means the multi-modular inverter can be free from turn-on loss. In summary, this dissertation focuses on developing modulation methods for inverters based on the series resonant converter. Soft-switching feature and high efficiency are the two top priorities. The analytic and experimental results are provided based on standalone applications. / Doctor of Philosophy / Inverters are an important part of a modern electric power system, as they convert dc electric power into ac electric power. In some applications, inverters with electrical insulation (isolated inverters) are preferred due to the need for engineering freedom, safety, and other reasons. However, each conventional isolated inverter has some of the following drawbacks: hard-switching in semiconductor devices, high circulating current, poor transformer utilization, and high complexity. These drawbacks limit the efficiency and compactness of an inverter system, making the system less attractive to practical applications. An inverter based on a series resonant converter seems to be a solution because the series resonant converter is known for being simple and highly-efficient. However, there has yet to be a proper modulation method for it. Therefore, the main contribution of this dissertation is to propose a hybrid modulation method. With the proposed method, the inverter can operate with high efficiency. Furthermore, the hard-switching can be well suppressed, which means a high-frequency, compact design is possible. Besides the theory of the proposed method, this dissertation also includes a power loss model, a hardware design procedure, and analytic comparisons with other methods. In addition, a digital approach to control the inverter is proposed. Without it, the output voltage waveform may be highly distorted. Finally, another sequential control strategy is proposed in this dissertation for an integrated system. The integrated system is composed of multiple inverters based on a series resonant converter. With the sequential control strategy, the overall output waveform quality of the integrated system can be improved.