Antipodal random sequences with prescribed second-order statistics: application to Compressive Sensing and UWB system based on DS-CDMA

It is usual to hear a strange short sentence: «Random is better than...». Why is randomness a good solution to a certain engineering problem? There are many possible answers, and all of them are related to the considered topic. In this thesis I will discuss about two crucial topics that take advantage by randomizing some waveforms involved in signals manipulations. In particular, advantages are guaranteed by shaping the second order statistic of antipodal sequences involved in an intermediate signal processing stages. The first topic is in the area of analog-to-digital conversion, and it is named Compressive Sensing (CS). CS is a novel paradigm in signal processing that tries to merge signal acquisition and compression at the same time. Consequently it allows to direct acquire a signal in a compressed form. In this thesis, after an ample description of the CS methodology and its related architectures, I will present a new approach that tries to achieve high compression by design the second order statistics of a set of additional waveforms involved in the signal acquisition/compression stage. The second topic addressed in this thesis is in the area of communication system, in particular I focused the attention on ultra-wideband (UWB) systems. An option to produce and decode UWB signals is direct-sequence spreading with multiple access based on code division (DS-CDMA). Focusing on this methodology, I will address the coexistence of a DS-CDMA system with a narrowband interferer. To do so, I minimize the joint effect of both multiple access (MAI) and narrowband (NBI) interference on a simple matched filter receiver. I will show that, when spreading sequence statistical properties are suitably designed, performance improvements are possible with respect to a system exploiting chaos-based sequences minimizing MAI only.

Heterogeneous Multi-core Architectures for High Performance Computing

This thesis deals with heterogeneous architectures in standard workstations. Heterogeneous architectures represent an appealing alternative to traditional supercomputers because they are based on commodity components fabricated in large quantities. Hence their price-performance ratio is unparalleled in the world of high performance computing (HPC). In particular, different aspects related to the performance and consumption of heterogeneous architectures have been explored. The thesis initially focuses on an efficient implementation of a parallel application, where the execution time is dominated by an high number of floating point instructions. Then the thesis touches the central problem of efficient management of power peaks in heterogeneous computing systems. Finally it discusses a memory-bounded problem, where the execution time is dominated by the memory latency. Specifically, the following main contributions have been carried out: A novel framework for the design and analysis of solar field for Central Receiver Systems (CRS) has been developed. The implementation based on desktop workstation equipped with multiple Graphics Processing Units (GPUs) is motivated by the need to have an accurate and fast simulation environment for studying mirror imperfection and non-planar geometries. Secondly, a power-aware scheduling algorithm on heterogeneous CPU-GPU architectures, based on an efficient distribution of the computing workload to the resources, has been realized. The scheduler manages the resources of several computing nodes with a view to reducing the peak power. The two main contributions of this work follow: the approach reduces the supply cost due to high peak power whilst having negligible impact on the parallelism of computational nodes. from another point of view the developed model allows designer to increase the number of cores without increasing the capacity of the power supply unit. Finally, an implementation for efficient graph exploration on reconfigurable architectures is presented. The purpose is to accelerate graph exploration, reducing the number of random memory accesses.

Many-Core Architectures: Hardware-Software Optimization and Modeling Techniques

During the last few decades an unprecedented technological growth has been at the center of the embedded systems design paramount, with Moore’s Law being the leading factor of this trend. Today in fact an ever increasing number of cores can be integrated on the same die, marking the transition from state-of-the-art multi-core chips to the new many-core design paradigm. Despite the extraordinarily high computing power, the complexity of many-core chips opens the door to several challenges. As a result of the increased silicon density of modern Systems-on-a-Chip (SoC), the design space exploration needed to find the best design has exploded and hardware designers are in fact facing the problem of a huge design space. Virtual Platforms have always been used to enable hardware-software co-design, but today they are facing with the huge complexity of both hardware and software systems. In this thesis two different research works on Virtual Platforms are presented: the first one is intended for the hardware developer, to easily allow complex cycle accurate simulations of many-core SoCs. The second work exploits the parallel computing power of off-the-shelf General Purpose Graphics Processing Units (GPGPUs), with the goal of an increased simulation speed. The term Virtualization can be used in the context of many-core systems not only to refer to the aforementioned hardware emulation tools (Virtual Platforms), but also for two other main purposes: 1) to help the programmer to achieve the maximum possible performance of an application, by hiding the complexity of the underlying hardware. 2) to efficiently exploit the high parallel hardware of many-core chips in environments with multiple active Virtual Machines. This thesis is focused on virtualization techniques with the goal to mitigate, and overtake when possible, some of the challenges introduced by the many-core design paradigm.

Corpus callosum index and long-term disability in multiple sclerosis patients

Prediction of long-term disability in patients with multiple sclerosis (MS) is essential. Magnetic resonance imaging (MRI) measurement of brain volume may be of predictive value but sophisticated MRI techniques are often inaccessible in clinical practice. The corpus callosum index (CCI) is a normalized measurement that reflects changes of brain volume. We investigated medical records and 533 MRI scans at diagnosis and during clinical follow-up of 169 MS patients (mean age 42 +/- 11 years, 86% relapsing-remitting MS, time since first relapse 11 +/- 9 years). CCI at diagnosis was 0.345 +/- 0.04 and correlated with duration of disease (p = 0.002; r = -0.234) and expanded disability status scale (EDSS) score at diagnosis (r = -0.428; p < 0.001). Linear regression analyses identified age, duration of disease, relapse rate and EDSS at diagnosis as independent predictors for disability after mean of 7.1 years (Nagelkerkes' R:0.56). Annual CCI decrease was 0.01 +/- 0.02 (annual tissue loss: 1.3%). In secondary progressive MS patients, CCI decrease was double compared to that in relapsing-remitting MS patients (p = 0.04). There was a trend of greater CCI decrease in untreated patients compared to those who received disease modifying drugs (p = 0.2). CCI is an easy to use MRI marker for estimating brain atrophy in patients with MS. Brain atrophy as measured with CCI was associated with disability progression but it was not an independent predictor of long-term disability.

Integrating novel agents into multiple myeloma treatment - current status in Switzerland and treatment recommendations

The treatment of multiple myeloma has undergone significant changes in the recent past. The arrival of novel agents, especially thalidomide, bortezomib and lenalidomide, has expanded treatment options and patient outcomes are improving significantly. This article summarises the discussions of an expert meeting which was held to debate current treatment practices for multiple myeloma in Switzerland concerning the role of the novel agents and to provide recommendations for their use in different treatment stages based on currently available clinical data. Novel agent combinations for the treatment of newly diagnosed, as well as relapsed multiple myeloma are examined. In addition, the role of novel agents in patients with cytogenetic abnormalities and renal impairment, as well as the management of the most frequent side effects of the novel agents are discussed. The aim of this article is to assist in treatment decisions in daily clinical practice to achieve the best possible outcome for patients with multiple myeloma.

Symptomatic therapy in multiple sclerosis: a review for a multimodal approach in clinical practice

As more investigations into factors affecting the quality of life of patients with multiple sclerosis (MS) are undertaken, it is becoming increasingly apparent that certain comorbidities and associated symptoms commonly found in these patients differ in incidence, pathophysiology and other factors compared with the general population. Many of these MS-related symptoms are frequently ignored in assessments of disease status and are often not considered to be associated with the disease. Research into how such comorbidities and symptoms can be diagnosed and treated within the MS population is lacking. This information gap adds further complexity to disease management and represents an unmet need in MS, particularly as early recognition and treatment of these conditions can improve patient outcomes. In this manuscript, we sought to review the literature on the comorbidities and symptoms of MS and to summarize the evidence for treatments that have been or may be used to alleviate them.

Cortical morphometry in narcolepsy with cataplexy

The sleep-wake disorder narcolepsy with cataplexy is associated with the loss of hypocretin-(orexin-) producing neurons in the lateral hypothalamus. Several studies have reported abnormal cerebral activation in patients with narcolepsy with cataplexy. It remains unclear, however, whether these functional changes are related to structural alterations, particularly at the cortical level. To quantify structural brain changes associated with narcolepsy with cataplexy, we used high-resolution T1-weighted magnetic resonance imaging (MRI) in 12 patients compared with 12 healthy participants matched for age and gender. Subcortical and regional cortical volumes were measured using a method unbiased by non-linear registration. Further whole-brain analyses were conducted, measuring cortical characteristics, such as cortical thickness and gyrification, at thousands of points across each hemisphere using validated algorithms. Statistical analyses accounted for an effect of age and gender. We observed decreased cortical volume in the left paracentral lobule and increased cortical volume in the left caudal part of the middle frontal gyrus in narcoleptic patients compared with controls. Cortical thickness in prefrontal areas was inversely correlated with the severity of narcolepsy. Further, we observed several clusters of cortical thinning in patients with childhood or adolescent onset of narcolepsy compared with patients with adult onset of the disease. Our results suggest that specific anatomical changes may differentiate subgroups of narcolepsy patients with different clinical profiles (such as varying symptom severity or different age at onset). Future studies with larger groups of sleepy patients are required to assess whether distinct patterns of anatomical changes may distinguish narcolepsy from non-hypocretin-deficient hypersomnia disorders.

Limb apraxia in multiple sclerosis: prevalence and impact on manual dexterity and activities of daily living

To evaluate the prevalence and impact of limb apraxia on manual dexterity and activities of daily living (ADLs) in patients with multiple sclerosis (MS).

Impaired immune evasion in HIV through intracellular delays and multiple infection of cells

With its high mutation rate, HIV is capable of escape from recognition, suppression and/or killing by CD8(+) cytotoxic T lymphocytes (CTLs). The rate at which escape variants replace each other can give insights into the selective pressure imposed by single CTL clones. We investigate the effects of specific characteristics of the HIV life cycle on the dynamics of immune escape. First, it has been found that cells in HIV-infected patients can carry multiple copies of proviruses. To investigate how this process affects the emergence of immune escape, we develop a mathematical model of HIV dynamics with multiple infections of cells. Increasing the frequency of multiple-infected cells delays the appearance of immune escape variants, slows down the rate at which they replace the wild-type variant and can even prevent escape variants from taking over the quasi-species. Second, we study the effect of the intracellular eclipse phase on the rate of escape and show that escape rates are expected to be slower than previously anticipated. In summary, slow escape rates do not necessarily imply inefficient CTL-mediated killing of HIV-infected cells, but are at least partly a result of the specific characteristics of the viral life cycle.

OPTIMIZING A SHORT-END ELECTROPHORETICALLY MEDIATED MICRO-ANALYSIS (EMMA) ASSAY FOR CREATININE

In this work electrophoretically mediated micro-analysis (EMMA) is used in conjunction with short end injection to improve the in-capillary Jaffé assay for creatinine. Key advances over prior work include (i) using simulation to ensure intimate overlap of reagent plugs, (ii) using OH- to drive the reaction, (iii) using short-end injection to minimize analysis time and in-line product degradation. The potential-driven overlapping time with the EMMA approach, as well as the borate buffer background electrolyte (BGE) concentration and pH are optimized with the short end approach. The best conditions for short-end analyses would not have been predicted by the prior long end work, owing to a complex interplay of separation time and product degradation rates. Raw peak areas and flow-adjusted peak areas for the Jaffé reaction product (at 505 nm) are used to assess the sensitivity of the short-end EMMA approach. Optimal overlap conditions depend heavily on local conductivity differences within the reagent zone(s), as these differences cause dramatic voltage field differences, which effect reagent overlap dynamics. Simul 5.0, a dynamic simulation program for capillary electrophoresis (CE) systems, is used to understand the ionic boundaries and profiles that give rise to the experimentally obtained data for EMMA analysis. Overall, fast migration of hydroxide ions from the picrate zone makes difficult reagent overlap. In addition, the challenges associated with the simultaneous overlapping of three reagent zones are considered, and experimental results validate the predictions made by the simulation. With one set of “optimized” conditions including OH- (253 mM) as the third reagent zone the response was linear with creatinine concentration (R2 = 0.998) and reproducible over the clinically relevant range (0.08 to 0.1 mM) of standard creatinine concentrations. An LOD (S/N = 3) of 0.02 mM and LOQ (S/N=10) of 0.08 mM were determined. A significant improvement (43%) in assay sensitivity was obtained compared to prior work that considered only two reagents in the overlap.

Detrital Zircon Evidence for Mixing of Mazatzal Province Age Detritus With Yavapai Age (ca. 1700-1740 Ma) and Older Detritus in the ca. 1650 Ma Mazatzal Province of Central New Mexico, USA

Preliminary detrital zircon age distributions from Mazatzal crustal province quartzite and schist exposed in the Manzano Mountains and Pedernal Hills of central New Mexico are consistent with a mixture of detritus from Mazatzal age (ca. 1650 Ma), Yavapai age (ca. 1720 Ma.), and older sources. A quartzite sample from the Blue Springs Formation in the Manzano Mountains yielding 67 concordant grain analyses shows two dominant age peaks of 1737 Ma and 1791 Ma with a minimum peak age of 1652 Ma. Quartzite and micaceous quartzite samples from near Pedernal Peak give unimodal peak ages of ca. 1695 Ma and 1738 Ma with minimum detrital zircon ages of ca. 1625 Ma and 1680 Ma, respectively. A schist sample from the southern exposures of the Pedernal Hills area gives a unimodal peak age of 1680 Ma with a minimum age of ca. 1635 Ma. Minor amounts of older detritus (>1800 Ma) possibly reflect Trans-Hudson, Wyoming, Mojave Province, and older Archean sources and aid in locating potential source terrains for these detrital zircon. The Blue Springs Formation metarhyolite from near the top of the Proterozoic section in the Manzano Mountains yields 71 concordant grains that show a preliminary U-Pb zircon crystallization age of 1621 ¿ 5 Ma, which provides a minimum age constraint for deposition in the Manzano Mountains. Normalized probability plots from this study are similar to previously reported age distributions in the Burro and San Andres Mountains in southern New Mexico and suggest that Yavapai Province age detritus was deposited and intermingled with Mazatzal Province age detritus across much of the Mazatzal crustal province in New Mexico. This data shows that the tectonic evolution of southwestern Laurentia is associated with multiple orogenic events. Regional metamorphism and deformation in the area must postdate the Mazatzal Orogeny and ca. 1610 Ma ¿ 1620 Ma rhyolite crystallization and is attributed to the Mesoproterozoic ca. 1400 ¿ 1480 Ma Picuris Orogeny.

Dysferlin is a new marker for leaky brain blood vessels in multiple sclerosis

Dysferlin is a muscle protein involved in cell membrane repair and its deficiency is associated with muscular dystrophy. We describe that dysferlin is also expressed in leaky endothelial cells. In the normal central nervous system (CNS), dysferlin is only present in endothelial cells of circumventricular organs. In the inflamed CNS of patients with multiple sclerosis (MS) or in animals with experimental autoimmune encephalomyelitis, dysferlin reactivity is induced in endothelial cells and the expression is associated with vascular leakage of serum proteins. In MS, dysferlin expression in endothelial cells is not restricted to vessels with inflammatory cuffs but is also present in noninflamed vessels. In addition, many blood vessels with perivascular inflammatory infiltrates lack dysferlin expression in inactive lesions or in the normal-appearing white matter. In vitro, dysferlin can be induced in endothelial cells by stimulation with tumor necrosis factor-alpha. Hence, dysferlin is not only a marker for leaky brain vessels, but also reveals dissociation of perivascular inflammatory infiltrates and blood-brain barrier disturbance in multiple sclerosis.

Microcystic serous cystadenoma of the pancreas: a report of two cases with one of diffuse presentation

Microcystic adenoma or serous cystadenoma is an uncommon tumor and accounts for 1-2% of the exocrine neoplasms of the pancreas. Usually unifocal, they present as single, large, well-demarcated multiloculated cystic tumors, ranging in size from 1 to 25 cm. Multifocal variants or diffuse serous cystadenomas are extremely rare. We present 2 cases of which 1 is a diffuse variant affecting the body, tail and part of the neck of the pancreas. In both the patients the tumors were detected incidentally. We highlight on the diffuse variant in view of its rarity and present a review of literature. In this case the entire body and tail of the pancreas was spongy replaced by multicystic lobules and hyalinized fibrocollagenous stroma. The cysts were lined by low cuboidal glycogen containing bland cells. Such a unique presentation wherein the entire body and tail of the pancreas is replaced with multiple cysts is a diffuse presentation of microcystic adenoma and a search through literature revealed only 7 such cases among the 15 cases with multifocal presentation reported.

Whole-body MRI of multiple myeloma: comparison of different MRI sequences in assessment of different growth patterns

PURPOSE: To determine sensitivity, specificity and inter-observer variability of different whole-body MRI (WB-MRI) sequences in patients with multiple myeloma (MM). METHODS AND MATERIALS: WB-MRI using a 1.5T MRI scanner was performed in 23 consecutive patients (13 males, 10 females; mean age 63+/-12 years) with histologically proven MM. All patients were clinically classified according to infiltration (low-grade, n=7; intermediate-grade, n=7; high-grade, n=9) and to the staging system of Durie and Salmon PLUS (stage I, n=12; stage II, n=4; stage III, n=7). The control group consisted of 36 individuals without malignancy (25 males, 11 females; mean age 57+/-13 years). Two observers independently evaluated the following WB-MRI sequences: T1w-TSE (T1), T2w-TIRM (T2), and the combination of both sequences, including a contrast-enhanced T1w-TSE with fat-saturation (T1+/-CE/T2). They had to determine growth patterns (focal and/or diffuse) and the MRI sequence that provided the highest confidence level in depicting the MM lesions. Results were calculated on a per-patient basis. RESULTS: Visual detection of MM was as follows: T1, 65% (sensitivity)/85% (specificity); T2, 76%/81%; T1+/-CE/T2, 67%/88%. Inter-observer variability was as follows: T1, 0.3; T2, 0.55; T1+/-CE/T2, 0.55. Sensitivity improved depending on infiltration grade (T1: 1=60%; 2=36%; 3=83%; T2: 1=70%; 2=71%; 3=89%; T1+/-CE/T2: 1=50%; 2=50%; 3=89%) and clinical stage (T1: 1=58%; 2=63%; 3=79%; T2: 1=58%; 2=88%; 3=100%; T1+/-CE/T2: 1=50%; 2=63%; 3=100%). T2w-TIRM sequences achieved the best reliability in depicting the MM lesions (65% in the mean of both readers). CONCLUSIONS: T2w-TIRM sequences achieved the highest level of sensitivity and best reliability, and thus might be valuable for initial assessment of MM. For an exact staging and grading the examination protocol should encompass unenhanced and enhanced T1w-MRI sequences, in addition to T2w-TIRM.

Whole-body computed tomography for multiple traumas using a triphasic injection protocol

To evaluate a triphasic injection protocol for whole-body multidetector computed tomography (MDCT) in patients with multiple trauma. Fifty consecutive patients (41 men) were examined. Contrast medium (300 mg/mL iodine) was injected starting with 70 mL at 3 mL/s, followed by 0.1 mL/s for 8 s, and by another bolus of 75 mL at 4 mL/s. CT data acquisition started 50 s after the beginning of the first injection. Two experienced, blinded readers independently measured the density in all major arteries, veins, and parenchymatous organs. Image quality was assessed using a five-point ordinal rating scale and compared to standard injection protocols [n = 25 each for late arterial chest, portovenous abdomen, and MDCT angiography (CTA)]. With the exception of the infrarenal inferior caval vein, all blood vessels were depicted with diagnostic image quality using the multiple-trauma protocol. Arterial luminal density was slightly but significantly smaller compared to CTA (P < 0.01). Veins and parenchymatous organs were opacified significantly better compared to all other protocols (P < 0.01). Arm artifacts reduced the density of spleen and liver parenchyma significantly (P < 0.01). Similarly high image quality is achieved for arteries using the multiple-trauma protocol compared to CTA, and parenchymatous organs are depicted with better image quality compared to specialized protocols. Arm artifacts should be avoided.