Abstract-Over the past several years, there has been a renewed interest in complex orthogonal designs for their application in space-time block coding. Motivated by the success of this application, this paper generalizes the definition of complex orthogonal designs by introducing orthogonal designs over the quaternion domain. This paper builds a theory of these novel quaternion orthogonal designs, offers examples, and provides several construction techniques. These theoretical results, along with the results of preliminary simulations, lay the foundation for developing applications of these designs as orthogonal space-time-polarization block codes.
Limitations of antiretroviral therapy (ART) include poor patient adherence, drug toxicities, viral resistance, and failure to penetrate viral reservoirs. Recent developments in nanoformulated ART (nanoART) could overcome such limitations. To this end, we now report a novel effect of nanoART that facilitates drug depots within intracellular compartments at or adjacent to the sites of the viral replication cycle. Poloxamer 407-coated nanocrystals containing the protease inhibitor atazanavir (ATV) were prepared by high-pressure homogenization. These drug particles readily accumulated in human monocyte-derived macrophages (MDM). NanoATV concentrations were ϳ1,000 times higher in cells than those that could be achieved by the native drug. ATV particles in late and recycling endosome compartments were seen following pulldown by immunoaffinity chromatography with Rab-specific antibodies conjugated to magnetic beads. Confocal microscopy provided cross validation by immunofluorescent staining of the compartments. Mathematical modeling validated drug-endosomal interactions. Measures of reverse transcriptase activity and HIV-1 p24 levels in culture media and cells showed that such endosomal drug concentrations enhanced antiviral responses up to 1,000-fold. We conclude that late and recycling endosomes can serve as depots for nanoATV. The colocalization of nano-ATV at endosomal sites of viral assembly and its slow release sped antiretroviral activities. Long-acting nanoART can serve as a drug carrier in both cells and subcellular compartments and, as such, can facilitate viral clearance. IMPORTANCEThe need for long-acting ART is significant and highlighted by limitations in drug access, toxicity, adherence, and reservoir penetrance. We propose that targeting nanoformulated drugs to infected tissues, cells, and subcellular sites of viral replication may improve clinical outcomes. Endosomes are sites for human immunodeficiency virus assembly, and increasing ART concentrations in such sites enhances viral clearance. The current work uncovers a new mechanism by which nanoART can enhance viral clearance over native drug formulations.
Modern communications systems are heavily reliant on statistical techniques to recover information in the presence of noise and interference. One of the mathematical structures used to achieve this goal is Hadamard matrices. They are used in many different ways and some examples are given. This paper concentrates on code division multiple access systems where Hadamard matrices are used for user separation. Two older techniques from design and analysis of experiments which rely on similar processes are also included. We give a short bibliography (from the thousands produced by a google search) of applications of Hadamard matrices appearing since the paper of Hedayat and Wallis in 1978 and some applications in telecommunications. Disciplines Physical Sciences and Mathematics Publication DetailsThis article was originally published as Seberry, J, Wysocki, Bj and Wysocki, TA, On some applications of Hadamard matrices, Metrika, 62, (2005) Abstract Modern communications systems are heavily reliant on statistical techniques to recover information in the presence of noise and interference. One of the mathematical structures used to achieve this goal is Hadamard matrices. They are used in many different ways and some examples are given. This paper concentrates on code division multiple access systems where Hadamard matrices are used for user separation. Two older techniques from design and analysis of experiments which rely on similar processes are also included. We give a short bibliography (from the thousands produced by a google search) of applications of Hadamard matrices appearing since the paper of Hedayat and Wallis in 1978 and some applications in telecommunications.
Gene delivery systems transport exogenous genetic information to cells or biological systems with the potential to directly alter endogenous gene expression and behavior with applications in functional genomics, tissue engineering, medical devices, and gene therapy. Nonviral systems offer advantages over viral systems because of their low immunogenicity, inexpensive synthesis, and easy modification but suffer from lower transfection levels. The representation of gene transfer using models offers perspective and interpretation of complex cellular mechanisms, including nonviral gene delivery where exact mechanisms are unknown. Here, we introduce a novel telecommunications model of the nonviral gene delivery process in which the delivery of the gene to a cell is synonymous with delivery of a packet of information to a destination computer within a packet‐switched computer network. Such a model uses nodes and layers to simplify the complexity of modeling the transfection process and to overcome several challenges of existing models. These challenges include a limited scope and limited time frame, which often does not incorporate biological effects known to affect transfection. The telecommunication model was constructed in MATLAB to model lipoplex delivery of the gene encoding the green fluorescent protein to HeLa cells. Mitosis and toxicity events were included in the model resulting in simulation outputs of nuclear internalization and transfection efficiency that correlated with experimental data. A priori predictions based on model sensitivity analysis suggest that increasing endosomal escape and decreasing lysosomal degradation, protein degradation, and GFP‐induced toxicity can improve transfection efficiency by three‐fold. Application of the telecommunications model to nonviral gene delivery offers insight into the development of new gene delivery systems with therapeutically relevant transfection levels. Biotechnol. Bioeng. 2014;111: 1659–1671. © 2014 Wiley Periodicals, Inc.
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