Transplantation is the best therapeutic solution for patients with chronic renal failure. Due to the great advances in immunosuppressive therapy in the last decades, graft and patient survival have improved significantly. On the other hand, immunosuppressive therapy has serious side effects - too strong immunosuppression may lead to infection or malignancies, conversely insufficient immunosuppression may lead to graft rejection. Due to the grave consequences of acute rejection, the main goal of cooperation of clinicians and transplant immunologists is to stratify patients into groups with low, moderate and high risk of rejection based on the evaluation of various immunologic risk factors. There are reports in the literature that the numbers (frequencies) of interferon gamma (IFNγ) producing cells before transplantation may be helpful to identify patients with high risk of acute cellular rejection and to predict long-term survival of the graft. In this retrospective study we determined the pre-transplant frequencies of activated donor specific T lymphocytes producing IFNγ after short stimulation (24 hrs) by ELISpot (Enzyme-linked immunosorbent spot assay). The results were correlated with the incidence of acute cellular (ACR) and antibody-mediated (AMR) rejection and with other risk factors. In our...

Current immunogenetic tests before organ transplantation include HLA typing and detection of HLA-specific antibodies. However, these tests do not provide information about the B cells participating in the humoral response against the transplanted organ. BAFF (B activating factor) plays an important role in the proliferation, maturation and differentiation of B cells. A soluble form of the cytokine arises after splicing the membrane form of BAFF. The soluble cytokine binds to three types of receptors - TACI, BCMA and BCMA. Some recent studies suggest that BAFF could serve as a marker or predictor of antibody-mediated (humoral) rejection in kidney transplant recipients. Our study consists of two parts. The first part is focused on the detection of soluble BAFF levels in patients after renal transplantation. The aim of our study was therefore to correlate levels of soluble BAFF cytokine in patients before and after transplantation with the clinical course and incidence of rejection after transplantation. The study included 92 kidney recipients. Humoral rejection was diagnosed on the basis of a positive finding of C4d deposits in peritubular capillaries (imunoflorescenční detection), and the presence of donor- specific antibodies. BAFF levels were determined using Xmap methodology by the Luminex method...

What factors predict whether we perceive rejection from our heritage culture? Few studies have examined the antecedents and outcomes of intragroup marginalisation – perceived rejection due to not conforming to the expectations of one’s heritage culture – in spite of its implications for the psychological functioning of bicultural individuals. The broad aims of this thesis are twofold: to provide a holistic insight into the predictors of intragroup marginalisation and, in turn, to investigate its impact on psychological adjustment and functioning. The General Introduction reviews existing acculturation and marginalisation research and situates intragroup marginalisation within the Social Identity Theory framework. It is noted that previous research on the marginalised experiences of bicultural individuals has centred on either their choice of dis-identifying with their heritage culture, or being prevented from identifying with the heritage culture by the mainstream culture. The role of the heritage culture in-group in rejecting non-conforming members has largely been neglected. The predictors of this perceived rejection from one’s heritage culture were chosen because of their importance in shaping interpersonal interactions and goals: attachment orientations, selfconstrual, and conservation values. In addition, perceived cultural distance between the heritage and mainstream cultures was included as a factor which may heighten the tension between one’s cultural identities. To provide broad insight into the detrimental impact of intragroup marginalisation, outcome variables were chosen that represent general psychological functioning: psychological adjustment (conceptualised as acculturative stress, subjective well-being, and flourishing), an integrated bicultural identity, and extreme progroup behaviour. Study 1 found that anxious and avoidant attachment orientations were associated with greater intragroup marginalisation and, in turn, with lower psychological adjustment. Study 2 experimentally primed attachment representations; results further supported the link between chronic attachment orientations and decreased intragroup marginalisation. Study 3 further supported the link between attachment avoidance and anxiety and increased intragroup marginalisation. Furthermore, support was found for the indirect effects of avoidant attachment through intragroup marginalisation on greater endorsement of extreme pro-group behaviours. Study 4 increased the cognitive accessibility of independent and interdependent self-construals through a priming manipulation. Primed interdependent self-construal exerted a protective effect against the link between intragroup marginalisation and poor psychological adjustment and a conflicted bicultural identity, whilst primed independent self-construal was linked with increased intragroup marginalisation, and, in turn, decreased psychological adjustment. Study 5 indicated that valuing security and perceiving cultural distance decreased intragroup marginalisation, whilst valuing tradition marginally increased perceptions of intragroup marginalisation. Study 6 examined intragroup marginalisation experiences longitudinally. Results indicated that an increase in intragroup marginalisation from Time 1 to Time 2 was associated with an increase in acculturative stress. The General Discussion reviews the general findings, discusses implications for bicultural individuals, and sets further directions for research.

Bien que le rejet humoral en transplantation rénale soit de mieux en mieux caractérisé, des difficultés diagnostiques persistent et son pronostic reste sombre. Objectifs : dans un tel contexte, nous avons privilégié 2 objectifs : (1) préciser les mécanismes physiopathologiques en cause lorsque des signes d’inflammation microvasculaire tels qu’une glomérulite sont observés isolément sur biopsie systématique ; (2) évaluer le rôle de l’autoimmunité au cours de la transplantation dans le but d’identifier d’éventuels marqueurs prédictifs d’une évolution particulière au cours de la greffe. Méthodes : dans un premier temps, nous avons effectué une analyse clinico-pathologique d’une cohorte de 20 patients avec glomérulite isolée sur biopsie systématique à 3 mois de la greffe, couplée à un phénotypage par analyse transcriptomique. Après cette première étape, les distorsions du répertoire B induites par la greffe ont été évaluées de manière séquentielle par technique d’immuno-empreinte chez 43 patients transplantés rénaux dans l’optique de la caractérisation éventuelle de nouveaux biomarqueurs à valeur diagnostique et pronostique. Résultats et conclusion : il n’y avait pas de différence significative à 3 ans de la transplantation entre le groupe de patients avec glomérulite isolée et le groupe témoin.Cependant, la cohorte de patients étudiée est hétérogène puisqu’une évolution péjorative a été observée chez une minorité de patients, pour lesquels des anticorps anti-HLA (non spécifiques du donneur) étaient plus souvent présents et le grade lésionnel plus élevé. L’étude du répertoire B illustre l’importante hétérogénéité interindividuelle des profils de réactivitévis à vis du tissu rénal. Après transplantation, l’apparition de bandes de réactivité additionnelles était notée chez 19/43 patients, et ce dans toutes les catégories anatomocliniques représentées. L’identification des cibles antigéniques est un complément indispensable de cette approche. / X

Renal transplantation is the optimum treatment for end-stage renal failure. B cells have been identified in chronic allograft damage (CAD) and are associated with the development of tertiary lymphoid tissue within the human renal allograft. To investigate this pathology we utilized a mouse model of renal transplantation. A mouse model of kidney transplantation was first described in 1973. Although the mouse model is technically difficult it is attractive for several reasons: the mouse genome has been characterized and in many aspects is similar to man and there is a greater diversity of experimental reagents and techniques available for mouse studies than other experimental models. We reviewed the literature on all studies of mouse kidney transplantation to report the donor and recipient strain combinations that have been investigated and the resultant survival and histological outcomes. Some models of kidney transplantation have used the transplanted kidney as a life-supporting organ, however in many studies the recipient mouse’s native kidney has been left in situ. Several different combinations of inbred mouse strains have been reported, with varying degrees of injury, survival, or tolerance due to haplotype differences. Both cellular and humoral rejection processes have been observed. This model has been exceptionally useful as an investigational tool to understand multiple aspects of transplantation including acute rejection, cellular and humoral rejection mechanisms and their treatment. Furthermore this model has been used to investigate disease mechanisms beyond transplant rejection including intrinsic renal disease and infection-associated pathology. We performed renal transplantation in mice to model CAD and identified B cells forming tertiary lymphoid tissue with germinal centres. Intra-allograft B220+ B cells comprised of IgMhigh CD23- marginal zone, IgMlo CD23+ follicular zone and IgMlo CD23- transitional-type B cells similar to spleen, and these compartments had elevated expression of CD86. Depletion of B cells with anti-CD20 was associated with an improvement in CAD but only when administered after transplantation and not before. Isolated intra-allograft B cells were cultured and shown to synthesise multiple cytokines, the most abundant of these being GRO-α (CXCL1), RANTES (CCL5), IL-6 and MCP-1 (CCL2). Tubular loss was associated with T cell mediated injury and interstitial fibrosis, whilst type III collagen deposition driven by F4/80+ macrophages and PDGFR-β+ and transgelin+ fibroblasts, all of which were reduced by B cell depletion. In this report we show that intra-allograft B cells are key mediators of chronic damage to the transplant allograft kidney by cytokine orchestration of T cell, macrophage infiltration and fibroblast activation.

Biopotential signals are important to physicians for diagnosing medical conditions in patients. Traditionally, biopotentials are acquired using contact electrodes together with instrumentation amplifiers (INAs). The biopotentials are generally weak and in the presence of stronger common mode signals. The INA thus needs to have very good Common Mode Rejection Ratio (CMRR) to amplify the weak biopotential while rejecting the stronger common mode interferers. Opamp based INAs with a resistor-capacitor feedback are suitable for acquiring biopotentials with low power and low noise performance. However, CMRR of such INA topologies is typically very poor. In the presented research, a technique is proposed for improving the CMRR of opamp based INAs in RC feedback configurations by dynamically matching input and feedback capacitor pairs. Two instrumentation amplifiers (one fully differential and the other fully balanced fully symmetric) are designed with the proposed dynamic element matching scheme. Post layout simulation results show that with 1 percent mismatch between the limiting capacitor pairs, CMRR is improved to above 150dB when the proposed dynamic element matching scheme is used. The INAs draw about 10uA of quiescent current from a 1.5 dual power supply source. The input referred noise of the INAs is less than 3uV/sqrt(Hz).

No description available.

An FM transmitter becomes the new feature in recent portable electronic development. A low power, integrable FM transmitter filter IC is required to meet the demand of FM transmitting feature. A low pass filter using harmonic rejection technique along with a low power class-AB output buffer is designed to meet the current market requirements on the FM transmitter chip. A harmonic rejection filter is designed to filter FM square wave signal from 70MHz to 110MHz into FM sine wave signal. Based on Fourier series, the harmonic rejection technique adds the phase shifted square waves to achieve better THD and less high frequency harmonics. The phase shifting is realized through a frequency divider, and the summation is implemented through a current summation circuit. A RC low pass filter with automatic tuning is designed to further attenuate unwanted harmonics. In this work, the filter's post layout simulation shows -53dB THD and harmonics above 800MHz attenuation of -99dB. The power consumption of the filter is less than 0.7mW. Output buffer stage is implemented through a resistor degenerated transconductor and a class-AB amplifier. Feedforward frequency compensation is applied to compensate the output class-AB stage, which extends the amplifier's operating bandwidth. A fully balanced class-AB driver is proposed to unleash the driving capability of common source output transistors. The output buffer reaches -43dB THD at 110MHz with 0.63Vpp output swing and drives 1mW into 50 load. The power consumption of the output buffer is 7.25mW. By using harmonic rejection technique, this work realizes the 70MHz-110MHz FM carrier filtering using TSMC 0.18um nominal process. Above 800MHz harmonics are attenuated to below -95dB. With 1.2V supply, the total power consumption including output buffer is 7.95mW. The total die area is 0.946mm2.

Due to the uncertainties introduced by the propagation channel, and RF and mixed signal circuits imperfections, digital communication receivers require efficient and robust signal acquisition algorithms for timing and carrier recovery, and interfer- ence rejection. The main theme of this work is the development of efficient and robust signal synchronization and interference rejection schemes for narrowband, wideband and ultra wideband communications systems. A series of novel signal acquisition schemes together with their performance analysis and comparisons with existing state-of-the- art results are introduced. The design effort is first focused on narrowband systems, and then on wideband and ultra wideband systems. For single carrier modulated narrowband systems, it is found that conventional timing recovery schemes present low efficiency, e.g., certain feedback timing recov- ery schemes exhibit the so-called hang-up phenomenon, while another class of blind feedforward timing recovery schemes presents large self-noise. Based on a general re- search framework, we propose new anti-hangup algorithms and prefiltering techniques to speed up the feedback timing recovery and reduce the self-noise of feedforward tim- ing estimators, respectively. Orthogonal frequency division multiplexing (OFDM) technique is well suited for wideband wireless systems. However, OFDM receivers require high performance car-rier and timing synchronization. A new coarse synchronization scheme is proposed for efficient carrier frequency offset and timing acquisition. Also, a novel highly accurate decision-directed algorithm is proposed to track and compensate the residual phase and timing errors after the coarse synchronization step. Both theoretical analysis and computer simulations indicate that the proposed algorithms greatly improve the performance of OFDM receivers. The results of an in-depth study show that a narrowband interference (NBI) could cause serious performance loss in multiband OFDMbased ultra-wideband (UWB) sys- tems. A novel NBI mitigation scheme, based on a digital NBI detector and adaptive analog notch filter bank, is proposed to reduce the effects of NBI in UWB systems. Simulation results show that the proposed NBI mitigation scheme improves signifi- cantly the performance of a standard UWB receiver (this improvement manifests as a signal-to-noise ratio (SNR) gain of 9 dB).

Thesis (Ph. D.)--University of Texas at Austin, 2001. / Vita. Includes bibliographical references (leaves 141-150). Available also in a digital version from Dissertation Abstracts.