The Multi-Input Multi-Output (MIMO) Channel Modeling, Simulation and Applications

This thesis mainly focus on the Multi-Input Multi-Output (MIMO) channel modeling, simulation and applications. There are several ways to design a MIMO channel. Most of the examples are given in Chapter 2, where we can design channels based on the environments and also based on other conditions. One of the new MIMO channel designs based on physical and virtual channel design is discussed in Unitary-Independent- Unitary (UIU) channel modeling. For completeness, the different types of capacity are discussed in details. The capacity is very important in wireless communication. By understanding the details behind different capacity, we can improve our transmission efficiently and effectively. The level crossing rate and average duration are discussed.One of the most important topics in MIMO wireless communication is estimation. Without having the right estimation in channel prediction, the performance will not be correct. The channel estimation error on the performance of the Alamouti code was discussed. The design of the transmitter, the channel and the receiver for this system model is shown. The two different types of decoding scheme were shown - the linear combining scheme and the Maximum likelihood (ML) decoder. Once the reader understands the estimation of the MIMO channel, the estimation based on different antenna correlation is discussed. Next, the model for Mobile-to-Mobile (M2M) MIMO communication link is proposed. The old M2M Sum-of-Sinusoids simulation model and the new two ring models are discussed. As the last step, the fading channel modeling using AR model is derived and the effect of ill-conditioning of the Yule-Walker equation is also shown. A number of applications is presented to show how the performance can be evaluated using the proposed model and techniques

Polyomaviruses and disease: is there more to know than viremia and viruria?

Polyomavirus nephropathy (PVN) mainly caused by BK virus (BKV) remains the most common productive viral infection of the kidney. Over the past decade, clinical interest often focused on BK viremia and viruria as the diagnostic mainstays of patient management. The purpose of this review is to discuss viral nephropathy in the context of BK viremia and viruria and new strategies to optimize diagnostic accuracy and patient management. The emerging roles of polyomaviruses in oncogenesis, salivary gland disease, and post-bone marrow transplantation as well as novel Polyomavirus strains are highlighted

Gold nanoparticles: A promising therapeutic approach

Nanotechnology is rapidly advancing and will leave no field untouched by its ground breaking innovations. Nanoparticles are molecules with a diameter ranging from 10-100 nm. Nanotechnology has promising biomedical applications and most noteworthy amongst them are noble metal particles. For instance, gold nanoparticles (AuNPs) provide a unique blend of physical and optical properties, chemical inertness, and high surface to volume ratio. They can be synthesized as well as functionalised to support various ligands on their surface. Their surface functionalization and diverse properties render the gold nanoparticles highly useful for drug delivery and gene carrier for therapeutic purposes and as molecular probes for disease diagnosis. The foundation for the usage of AuNPs in therapeutics and diagnosis was laid by the ancient studies done with ruby gold for curing diseases in middle ages. Presently, AuNPs have become available in different types such as spheres, rods, shells, cages and SERS particles which vary in shape, size and physical properties. The biomedical applications of these particles include drug and gene delivery, cancer diagnosis and therapy, determination of biological molecules and microorganisms, detection of disease etiology, immunoassay, enzyme immobilization, etc. Overall, the focus of this review is to highlight that AuNPs provide an excellent platform for the discovery of new therapies, cure for certain cancers, molecular probe for diagnostic purposes, as well as gene carriers and drug delivery vehicles. Biomed Rev 2015; 26: 23-36.Key words: gold nanoparticles, cancer treatment, drug delivery system, gold nanocarrier therap

Boronic-diol complexation as click reaction for bioconjugation purposes

The research presented in this thesis focuses on the study of the reaction between boronic acids and diols and its evaluation as a possible "click" reaction, possibly applicable in bioconjugation and drug delivery. A key feature of this reaction is its reversibility at acidic pH, which could allow the release of a diol-containing drug from a bioconjugate in the acidic environment of late endosome/lysosome, possibly after undergoing receptor mediated endocytosis. Over the last two decades various studies have focused on the study of the conjugation of boronic acids to diols using Alizarin Red S as a fluorescence reporter. In this research we have presented an alternative method based on the batochromic shifts of Alizarin Red S absorbance; this method is particularly advantageous in complex systems with an elevated scattering, such as colloidal dispersions or for binding to complexed active compounds. We have therefore demonstrated that this method allows the determination of equilibrium constants between diols (e.g. catecholamines) and boronic acids. We have also demonstrated that the method allows to follow the kinetics of enzymatic reactions involving catechols; in particular, we have focused on cytochrome P450-mediated reactions such as the conversion of estradiol to 2-hydroxyestradiol using CYP1A2, or the demethylation of 3-methoxytyramine to dopamine using CYP2D6. Once we have established a reliable method for following this reaction on low molecular weight compounds, we have applied it to polymeric bioconjugates. Specifically, we have selected hyaluronic acid (HA) as a biocompatible and biodegradable polymeric backbone and produced derivatives containing boronic acids, catechols and dimethylated catechols (as negative controls). The resulting polymers where characterised via UV-Vis, 1H NMR and SLS, also qualitatively evaluating their cytotoxicity and enzymatic degradability. The conjugates with boronic acids showed the lowest cytotoxicity, and the highest degradability. The complexation of HA-boronic derivatives was then studied; using the same library of diols previously used with low molecular weight compounds, evaluating the effect of the presence of the polysaccharidic macromolecular chain.EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Antibody Drug Conjugates: A Leap Ahead in Cancer Treatment

Monoclonal antibody (MAb) based targeted therapies have achieved appreciable success in various branches of drug therapeutics, predominantly when used along with cytotoxic drugs. These immunological therapies based on antibody-drug conjugates (ADCs) have been recently encouraged by the US Food and Drug Administration to treat Solid tumours, Melanoma, Breast Cancer and Hodgkin’s lymphoma. Antibody drug conjugates (ADCs) are an important division of therapeutics that allows the antigen-selective ability of MAbs to deliver highly potent cytotoxic drugs at the site of antigen-expressing tumor cells. The use of MAb directed delivery can confer a high therapeutic index to highly potent cytotoxic drugs, increasing both the efficacy and safety of therapy. In other words, to achieve the goal of highly improved therapeutic efficacy and reduced toxicity, each component of an ADC i.e. the MAb, linker and the drug needs to be considered in context of targeted antigen. Furthermore, the mechanism of ADCs, characteristics of targets, methods of preparation, linker drugs being used in ADC design and regulatory requirements for new drug approval are discussed

Polyomavirus Nephropathy: Quantitative Urinary Polyomavirus-Haufen Testing Accurately Predicts the Degree of Intrarenal Viral Disease

BackgroundA qualitative highly predictive urinary test for polyomavirus nephropathy (PVN) is the PV-Haufen test. This article evaluates whether a quantitative PV-Haufen analysis, that is, the number of PV-Haufen shed per milliliter urine, predicts PVN disease grades and the severity of intrarenal PV replication.MethodsPolyomavirus-Haufen were counted in 40 urine samples from patients with biopsy-proven definitive PVN. The number of PV-Haufen was correlated with both histologic PVN disease grades 1 to 3 and the number of SV40-T–expressing cells as indicators of intrarenal PV replication in corresponding renal allograft biopsies (manual counts and automated morphometry). Findings from quantitative PV-Haufen analyses were compared to conventional laboratory test results, that is, BK viremia (quantitative polymerase chain reaction [PCR]) and BK viruria (quantitative PCR and decoy cell counts).ResultsPolyomavirus-Haufen counts showed excellent correlation (α0.77–0.86) with the severity of intrarenal PV replication and disease grades. In particular, low PV-Haufen numbers strongly correlated with early PVN grade 1 and minimal intrarenal expression of SV40-T antigen (P < 0.001). In comparison, BK viremia and viruria levels by PCR showed only modest correlations with histologic SV40-T expression (α0.40–0.49) and no significant correlation with disease grades or minimal intrarenal PV replication. No correlations were seen with urinary decoy cell counts. In contrast to conventional quantitative PCR assays or decoy cell counts, quantitative urinary PV-Haufen testing accurately reflects the severity of PV replication, tissue injury, and PVN disease grades.ConclusionsQuantitative PV-Haufen testing is a novel noninvasive approach to patient management for the diagnosis and prediction of PVN disease grades and monitoring of disease course during therapy.Quantitative testing of polyoma virus within shed renal tubule cells in the urine is superior to conventional BKV urinary or blood quantitation to define both the presence and degree of polyoma nephropathy. Supplemental digital content is available in the text

Temporal and Demographic Trends in Glomerular Disease Epidemiology in the Southeastern United States, 1986–2015

BACKGROUND AND OBJECTIVES: Large-scale, contemporary studies exploring glomerular disease epidemiology in the United States are lacking. We aimed to determine 30-year temporal and demographic trends in renal biopsy glomerular disease diagnosis frequencies in the southeastern United States. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this cross-sectional, observational study, we identified all patients with a native kidney biopsy specimen showing one of 18 widely recognized glomerular disease diagnoses referred to the University of North Carolina Chapel Hill Division of Nephropathology between 1986 and 2015. Biopsy era (1986-1995, 1996-2005, and 2006-2015) and demographics (age, sex, and race) were our primary and secondary predictors, respectively, and the relative frequency of each glomerular disease diagnosis was our primary outcome. RESULTS: Among 21,374 patients (mean age =48.3±18.3 years old; 50.8% men; 56.8% white; 38.3% black; 2.8% Latino; 1.4% Asian; 0.8% other), the frequency of diabetic glomerulosclerosis in renal biopsy specimens increased dramatically over the three decades (5.5%, 11.4%, and 19.1% of diagnoses, respectively; P for trend <0.001). The frequency of FSGS initially increased but then declined (22.6%, 27.2%, and 24.7%, respectively; P for trend =0.64). The frequencies of other common glomerular disease subtypes remained stable (IgA nephropathy and ANCA/pauci-immune GN) or declined (minimal change disease, membranous nephropathy, membranoproliferative GN, and lupus nephritis). These temporal trends were largely preserved within all demographic subgroups, although cross-sectional frequency distributions differed according to age, sex, and race. CONCLUSIONS: We identified significant changes in relative renal biopsy frequencies of many glomerular disease subtypes over three decades. Temporal trends were consistently observed within all major demographic groups, although relative predominance of individual glomerular disease subtypes differed according to patient age, sex, and race. We propose that exploration of behavioral and environmental exposures that likely underlie these findings should be the focus of future hypothesis-driven research