Human C-reactive protein (CRP) is the prototypic acute phase protein whose serum concentration increases rapidly during inflammation. CRP is also associated with atherosclerosis; it is deposited at lesion sites where it may interact with modified lipoproteins. There are 2 major questions regarding CRP: 1. How is the serum concentration of CRP regulated? 2. What are the functions of CRP in atherosclerosis? Our first aim was to determine the role of the constitutively expressed transcription factor Oct-1 in regulating CRP gene expression. We found that Oct-1 overexpression inhibited (IL-6+IL-1β)- induced CRP gene expression; maximal inhibition required the binding of Oct-1 to an octamer motif at (-59 to -66) on the CRP promoter. Oct-1 overexpression inhibited both (IL-6+IL-1β)- induced and C/EBPβ-induced CRP gene expression even when the Oct-1 site was deleted. These findings suggest that Oct-1 is a repressor of CRP gene expression that acts via binding to its cognate site on the CRP promoter as well as through indirect interactions with other promoterbound transcription factors. Our second aim was to investigate the interaction of CRP with oxidized low density lipoprotein (ox-LDL). Acidic pH, a hallmark of atherosclerotic lesions, reversibly alters CRP structure and exposes a hidden binding site that enables CRP to bind ox-LDL. Using site-directed mutagenesis we constructed a CRP mutant (E42Q) that showed significant binding to ox-LDL at physiological pH. E42Q CRP required a less acidic pH for maximal binding and bound ox-LDL more efficiently than wild type CRP at any pH. We then examined if reactive oxygen species also induced CRP – ox-LDL interaction. H2O2-treated CRP bound ox-LDL at physiological pH. Like acidic pH, H2O2-treatment induced only a local structural change exposing the ox-LDL binding site. E42Q and H2O2-modified CRP are tools to study the function of CRP in animal models of atherosclerosis, which may not have an inflammatory environment sufficient to modify CRP and induce binding to atherogenic ox-LDL. We conclude that Oct-1 is one of the critical regulators of CRP gene expression, and that CRP can be modified in vitro to convert it into an atherogenic LDL-binding molecule.

Abstract not available

Recent designs for low-density parity-check (LDPC) codes have exhibited capacity approaching performance for large block length, overtaking the performance of turbo codes. While theoretically impressive, LDPC codes present some challenges for practical implementation. In general, LDPC codes have higher encoding complexity than turbo codes both in terms of computational latency and architecture size. Decoder circuits for LDPC codes have a high routing complexity and thus demand large amounts of circuit area. There has been recent interest in developing analog circuit architectures suitable for decoding. These circuits offer a fast, low-power alternative to the digital approach. Analog decoders also have the potential to be significantly smaller than digital decoders. In this thesis we present a novel and efficient approach to LDPC encoder / decoder (codec) design. We propose a new algorithm which allows the parallel decoder architecture to be reused for iterative encoding. We present a new class of LDPC codes which are iteratively encodable, exhibit good empirical performance, and provide a flexible choice of code length and rate. Combining the analog decoding approach with this new encoding technique, we design a novel time-multiplexed LDPC codec, which switches between analog decode and digital encode modes. In order to achieve this behaviour from a single circuit we have developed mode-switching gates. These logic gates are able to switch between analog (soft) and digital (hard) computation, and represent a fundamental circuit design contribution. Mode-switching gates may also be applied to built-in self-test circuits for analog decoders. Only a small overhead in circuit area is required to transform the analog decoder into a full codec. The encode operation can be performed two orders of magnitude faster than the decode operation, making the circuit suitable for full-duplex applications. Throughput of the codec scales linearly with block size, for both encode and decode operations. The low power and small area requirements of the circuit make it an attractive option for small portable devices.

Le multicast fiable est certainement la solution la plus efficace pour la distribution de contenu via un<br />tres grand nombre (potentiellement des millions) de recepteurs. Dans cette perspective les protocoles<br />ALC et FLUTE, standardises via l'IETF (RMT WG), ont ete adoptes dans 3GPP/MBMS et dans le<br />DVB-H IP-Datacast dans les contextes des reseaux cellulaires 3G.<br />Ce travail se concentre sur le multicast fiable et a comme requis principal le passage l'echelle massif<br />en terme de nombre de clients. Cette these se base sur les solutions proposees via l'IETF RMT WG.<br />Ces protocoles de multicast fiable sont construit autour de plusieurs briques de base que nous avons<br />etudie en detail:<br />* La brique Forward Error Correction (FEC) :<br />Nous examinons la classe de codes grands blocs Low Density Parity Check (LDPC). Nous concevons<br />des derivees de ces codes, et les analysons en detail. Nous en concluons que les codes<br />LDPC et leur implementation ont des performances tres prometteuses, surtout si ils sont utilisees<br />avec des fichiers de taille importante.<br />* La brique controle de congestion :<br />Nous examinons le comportement dans la phase de demarrage de trois protocoles de controle de<br />congestion RLC, FLID-SL, WEBRC. Nous demontrons que la phase de demarrage a un grand<br />impact sur les performances de telechargement.<br />Cette these a aussi plusieurs contributions au niveau applicatif:<br />* Extensions de FLUTE :<br />Nous proposons un mecanisme permettant d'agreger plusieurs fichiers dans le protocole FLUTE.<br />Ceci ameliore les performance de transmission.<br />* Streaming video :<br />Nous proposons SVSoA, une solution de streaming base sur ALC. Cette approche beneficie de<br />tout les avantages de ALC en terme de passage a l'echelle, controle de congestion et corrections<br />d'erreurs.<br /><br />Mots cles : Multicast fiable, FLUTE, ALC, codes correcteur d'erreurs, Forward Error Correction<br />(FEC), Low Density Parity Check (LDPC) Codes, diffusion de contenu

<p>Recently, low-density parity-check (LDPC) codes have attracted much attention because of their excellent error correcting performance and highly parallelizable decoding scheme. However, the effective VLSI implementation of and LDPC decoder remains a big challenge and is a crucial issue in determining how well we can exploit the benefits of the LDPC codes in the real applications. In this master thesis report, following a error coding background, we describe Low-Density Parity-Check codes and their decoding algorithm, and also requirements and architectures of LPDC decoder implementations.</p>

<p>The family of Low Density Parity Check (LDPC) codes is a strong candidate to be used as Forward Error Correction (FEC) in future communication systems due to its strong error correction capability. Most LDPC decoders use the Message Passing algorithm for decoding, which is an iterative algorithm that passes messages between its variable nodes and check nodes. It is not until recently that computation power has become strong enough to make Message Passing on LDPC codes feasible. Although locally simple, the LDPC codes are usually large, which increases the required computation power. Earlier work on LDPC codes has been concentrated on the binary Galois Field, GF(2), but it has been shown that codes from higher order fields have better error correction capability. However, the most efficient LDPC decoder, the Belief Propagation Decoder, has a squared complexity increase when moving to higher order Galois Fields. Transmission over a channel with M-PSK signalling is a common technique to increase spectral efficiency. The information is transmitted as the phase angle of the signal.</p><p>The focus in this Master’s Thesis is on simplifying the Message Passing decoding when having inputs from M-PSK signals transmitted over an AWGN channel. Symbols from higher order Galois Fields were mapped to M-PSK signals, since M-PSK is very bandwidth efficient and the information can be found in the angle of the signal. Several simplifications of the Belief Propagation has been developed and tested. The most promising is the Table Vector Decoder, which is a Message Passing Decoder that uses a table lookup technique for check node operations and vector summation as variable node operations. The table lookup is used to approximate the check node operation in a Belief Propagation decoder. Vector summation is used as an equivalent operation to the variable node operation. Monte Carlo simulations have shown that the Table Vector Decoder can achieve a performance close to the Belief Propagation. The capability of the Table Vector Decoder depends on the number of reconstruction points and the placement of them. The main advantage of the Table Vector Decoder is that its complexity is unaffected by the Galois Field used. Instead, there will be a memory space requirement which depends on the desired number of reconstruction points.</p>

<p>Atherosclerosis is a progressive inflammatory disease that is characterized by the accumulation of lipids, infiltrated cells and fibrous elements in large arteries.</p><p>This thesis focuses on the molecular mechanisms behind foam cell formation and inflammation, two central processes in the development of atherosclerosis. More specific, we studied the effects of proinflammatory cytokines on CXCL16 expression and its role as scavenger receptor on macrophages and smooth muscle cells in atherogenesis. CXCL16 is defined as a chemokine and a scavenger receptor, regulating adhesion and chemoattraction of CXCR6 expressing cells and uptake of oxLDL. We show that the expression of CXCL16 and its receptor CXCR6 are more pronounced in human atherosclerotic lesions compared with non-atherosclerotic vessels. Increased expression of CXCL16 was also seen in atherosclerotic aortas of apoE-/- mice compared with aortas of non-atherosclerotic, age-matched C57BL/6 mice. In vitro, IFN gamma induced CXCL16 expression in primary human monocytes and smooth muscle cells which resulted in an increased uptake of oxLDL. Treatment of mice with IFN gamma also induced CXCL16 expression in atherosclerotic lesions. Thus, we have demonstrated a role for IFN gamma in foam cell formation through upregulation of CXCL16. The expression of CXCR6 was defined to the same regions as for CXCL16 in the lesion, indicating the presence of cells able to respond to CXCL16. Consequently, CXCL16 could serve as a molecular link between lipid metabolism and immune activity in atherosclerotic lesion.</p><p>CD137 belongs to the TNF family and mediates several important processes in inflammation. CD137 is involved in the activation of T cells, NK cells, B cells and monocytes and regulate cytokine production, proliferation and apoptosis in these cells. A limited number of studies have demonstrated CD137 expression on smooth muscle cells and endothelial cells. Our results show that CD137 mRNA is higher expressed in human atherosclerotic lesions compared with unaffected vessels. We found that endothelial cells express CD137 in atherosclerotic lesions and that cultured endothelial cells and smooth muscle cells express CD137 and CD137 ligand in vitro. CD137 was regulated differentially by proinflammatory cytokines (i.e. IFN gamma, TNF alpha, IL-1 beta) and bacterial lipopolysaccharide depending on cell type. Furthermore, we investigated the effects of CD137 signalling, demonstrating that binding of the CD137 ligand to its receptor increases proliferation and migration of smooth muscle cells.</p><p>In summary, this thesis has focused on the expression, regulation and role of CXCL16 and CD137, two genes that have not been described earlier in the concept of atherosclerosis. The findings demonstrate some of the molecular mechanisms involved in vascular inflammation and may increase our knowledge about the development of atherosclerosis.</p>

<p>In patients with unstable coronary artery disease (CAD) biochemical markers are emerging as useful tools in clinical management. In this thesis we studied the use of markers of low-density lipoprotein (LDL) oxidation and renal function.</p><p>Our study populations consisted of unstable CAD patients included in the Fast Revascularisation during Instability in Coronary artery disease (FRISC)-II trial and healthy controls. Patients were followed for 2 years regarding death and myocardial infarction (MI).</p><p>Using receiver operating characteristic curve analysis, we found that oxidized low-density lipoprotein (OxLDL), especially when combined with high-density lipoprotein, compared to traditionally measured lipids/lipoproteins, and a new lipoprotein marker, lipoprotein associated-phospholipase A2, was better at discriminating between healthy controls and CAD patients. In patients, OxLDL was found to be an independent prognostic marker associated with an increased risk of MI, of particular use in patients with no evidence of myocardial necrosis. </p><p>In our study on the effects of an early invasive treatment strategy in unstable CAD patients with mild to moderate renal dysfunction (i.e. creatinine clearance <90mL/min) we found that in patients randomized to invasive treatment, the rates of death/MI and MI alone were significantly lower than in patients randomized to non-invasive treatment. In patients treated invasively, no detrimental effects were seen on renal function at follow-up at 6 months. </p><p>In healthy controls, we investigated new markers of renal (cystatin C) and cardio-renal function (N-terminal probrain natriuretic peptide, [NT-proBNP]) regarding reference levels and physiological determinants. We found that cystatin C is influenced by age whereas NT-proBNP is influenced by age and gender.</p><p>Our studies suggest that OxLDL and renal dysfunction are associated with a poor prognosis in unstable CAD patients and that these markers demonstrate potential for clinical use. In the search for new markers related to renal function we have contributed with reference levels of cystatin C and NT-proBNP. </p>

In patients with unstable coronary artery disease (CAD) biochemical markers are emerging as useful tools in clinical management. In this thesis we studied the use of markers of low-density lipoprotein (LDL) oxidation and renal function. Our study populations consisted of unstable CAD patients included in the Fast Revascularisation during Instability in Coronary artery disease (FRISC)-II trial and healthy controls. Patients were followed for 2 years regarding death and myocardial infarction (MI). Using receiver operating characteristic curve analysis, we found that oxidized low-density lipoprotein (OxLDL), especially when combined with high-density lipoprotein, compared to traditionally measured lipids/lipoproteins, and a new lipoprotein marker, lipoprotein associated-phospholipase A2, was better at discriminating between healthy controls and CAD patients. In patients, OxLDL was found to be an independent prognostic marker associated with an increased risk of MI, of particular use in patients with no evidence of myocardial necrosis. In our study on the effects of an early invasive treatment strategy in unstable CAD patients with mild to moderate renal dysfunction (i.e. creatinine clearance &lt;90mL/min) we found that in patients randomized to invasive treatment, the rates of death/MI and MI alone were significantly lower than in patients randomized to non-invasive treatment. In patients treated invasively, no detrimental effects were seen on renal function at follow-up at 6 months. In healthy controls, we investigated new markers of renal (cystatin C) and cardio-renal function (N-terminal probrain natriuretic peptide, [NT-proBNP]) regarding reference levels and physiological determinants. We found that cystatin C is influenced by age whereas NT-proBNP is influenced by age and gender. Our studies suggest that OxLDL and renal dysfunction are associated with a poor prognosis in unstable CAD patients and that these markers demonstrate potential for clinical use. In the search for new markers related to renal function we have contributed with reference levels of cystatin C and NT-proBNP.

This thesis investigates channel-coded physical layer network coding, in which the relay directly transforms the noisy superimposed channel-coded packets received from the two end nodes, to the network-coded combination of the source packets. This is in contrast to the traditional multiple-access problem, in which the goal is to obtain each message explicitly at the relay. Here, the end nodes $A$ and $B$ choose their symbols, $S_A$ and $S_B$, from a small non-binary field, $\mathbb{F}$, and use non-binary PSK constellation mapper during the transmission phase. The relay then directly decodes the network-coded combination ${aS_A+bS_B}$ over $\mathbb{F}$ from the noisy superimposed channel-coded packets received from two end nodes. Trying to obtain $S_A$ and $S_B$ explicitly at the relay is overly ambitious when the relay only needs $aS_B+bS_B$. For the binary case, the only possible network-coded combination, ${S_A+S_B}$ over the binary field, does not offer the best performance in several channel conditions. The advantage of working over non-binary fields is that it offers the opportunity to decode according to multiple decoding coefficients $(a,b)$. As only one of the network-coded combinations needs to be successfully decoded, a key advantage is then a reduction in error probability by attempting to decode against all choices of decoding coefficients. In this thesis, we compare different constellation mappers and prove that not all of them have distinct performance in terms of frame error rate. Moreover, we derive a lower bound on the frame error rate performance of decoding the network-coded combinations at the relay. Simulation results show that if we adopt concatenated Reed-Solomon and convolutional coding or low density parity check codes at the two end nodes, our non-binary constellations can outperform the binary case significantly in the sense of minimizing the frame error rate and, in particular, the ternary constellation has the best frame error rate performance among all considered cases.