912 research outputs found

    Filter-Bank-Based Narrowband Interference Detection and Suppression in Spread Spectrum Systems

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    <p/> <p>A filter-bank-based narrowband interference detection and suppression method is developed and its performance is studied in a spread spectrum system. The use of an efficient, complex, critically decimated perfect reconstruction filter bank with a highly selective subband filter prototype, in combination with a newly developed excision algorithm, offers a solution with efficient implementation and performance close to the theoretical limit derived as a function of the filter bank stopband attenuation. Also methods to cope with the transient effects in case of frequency hopping interference are developed and the resulting performance shows only minor degradation in comparison to the stationary case.</p

    ON THE ROLE OF VIRUSES IN THE EVOLUTION OF IMMUNE RESPONSES

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    Mutual influences of viruses on the immune system and vice versa which lead to a biological balance are considered, with clinical and/or experimental findings. Numbers and turnover of immune cells can be correlated with numbers and growth rate of viruses; certain viruses apparently have adapted to systemic or local immune effector mechanisms. The biological balance of viruses and immune system guarentees overall protection of both host and parasite. It alos may lead to conditions where immune protective mechanisms causes cell and tissue damage leading to disease. Immunologically mediated disease may be influenced by immune regulation via HLA antigen and may therefore explain HLA-disease associations. Finally, the different specificities of antibodies vs. T Cells and the differing kinetics of their immunological memory are outlined and correlated with immune escape, immune protection and the resulting possible evolutionary pressures on viruse

    Fusoselect: cell-cell fusion activity engineered by directed evolution of a retroviral glycoprotein

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    Membrane fusion plays a key role in many biological processes including vesicle trafficking, synaptic transmission, fertilization or cell entry of enveloped viruses. As a common feature the fusion process is mediated by distinct membrane proteins. We describe here ‘Fusoselect', a universal procedure allowing the identification and engineering of molecular determinants for cell-cell fusion-activity by directed evolution. The system couples cell-cell fusion with the release of retroviral particles, but can principally be applied to membrane proteins of non-viral origin as well. As a model system, we chose a γ-retroviral envelope protein, which naturally becomes fusion-active through proteolytic processing by the viral protease. The selection process evolved variants that, in contrast to the parental protein, mediated cell-cell fusion in absence of the viral protease. Detailed analysis of the variants revealed molecular determinants for fusion competence in the cytoplasmic tail (CT) of retroviral Env proteins and demonstrated the power of Fusoselec

    Exploring epigenetic links: stress and albuminuria in youth with type 2 diabetes

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    Background: Youth with Type 2 Diabetes (T2D) often develop early-onset kidney disease, with albuminuria as the initial biomarker. Psychological factors, including perceived stress, are associated with the progression of kidney disease, although the mechanisms remain unclear. This study investigated DNA methylation changes in youth with T2D and albuminuria compared to those without albuminuria and examined whether changes in DNA methylation existed in genes known to be associated with stress functions. Methods: This cross-sectional study analyzed data from 213 youth with T2D enrolled in the national iCARE cohort study. Kidney injury was assessed by non-orthostatic albuminuria, and perceived stress was measured using the PSS-14 questionnaire. Whole blood DNA methylation patterns were analyzed using an epigenome-wide association study (EWAS) to identify differentially methylated sites. Associations with albuminuria were tested with multiple linear regression models. A differentially methylated region (DMR) analysis explored broader DNA methylation differences across the genome in areas related to kidney injury. A candidate gene analysis compared CpG sites from our study to the EWAS Atlas, with significance assessed using t-tests. Results: Based on the EWAS, no significant sites were associated with albuminuria. Six significant DMRs were identified, corresponding to the genes: TNXB, TSPAN32, ZNF486, ZNF562, ATP5E, and TNFRSF6B. These genes are linked to energy metabolism, immune regulation, and extracellular matrix maintenance. In the candidate gene analysis, we identified 56 CpG sites with significant differences at a p-value < 0.05 and 18 sites at a p-value < 0.01. Conclusion/Importance: Although no significant site-level differences were found, the six significant DMRs suggest potential regions of epigenetic variation that could be associated with stress and kidney injury in youth with T2D. Given the exploratory nature of these findings and the limitations of bloodbased DNA methylation studies, further research is needed to clarify the role of DNA methylation changes. These findings may help guide future investigations into the role of epigenetics in kidney injury and stress in youth-onset T2D.May 2025Rady Faculty of Health Sciences Graduate Studentship Award University of Manitoba Graduate Fellowship Manitoba Training Program for Health Services Researc

    GiViP: A Visual Profiler for Distributed Graph Processing Systems

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    Analyzing large-scale graphs provides valuable insights in different application scenarios. While many graph processing systems working on top of distributed infrastructures have been proposed to deal with big graphs, the tasks of profiling and debugging their massive computations remain time consuming and error-prone. This paper presents GiViP, a visual profiler for distributed graph processing systems based on a Pregel-like computation model. GiViP captures the huge amount of messages exchanged throughout a computation and provides an interactive user interface for the visual analysis of the collected data. We show how to take advantage of GiViP to detect anomalies related to the computation and to the infrastructure, such as slow computing units and anomalous message patterns.Comment: Appears in the Proceedings of the 25th International Symposium on Graph Drawing and Network Visualization (GD 2017

    Traditional Psychotria insularum vs. Western Medicine\u27s Ibuprofen: Parallels in Inflammation Reduction via Iron Chelation

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    Record ID: 257 Awards: Excellence in Research Mentoring Student Major: BS Biology, BFA Ballet, Pre-Medicine Certificate Project Advisor: Eric Tepe Abstract: Traditional medicinal plants contain an array of compounds which can be used for therapeutic purposes and as precursors for the synthesis of modern pharmaceuticals. Samoan traditional medicine is rather understudied, despite the astonishing effects it has shown amongst indigenous Samoan people. "Matalafi", the leaf homogenate of the coffee relative, Psychotria insularum, is habitually used in Samoan traditional medicine to treat inflammation. Matalafi has been shown to have powerful effects on the body, comparable to commonly used Ibuprofen. The focus of this study was to highlight both therapeutic and metabolic similarities between the effects of active compounds in P.insularum with modern day Ibuprofen. Through a study published in the Proceedings of the National Academy of Sciences of the United States of America, an iron homeostasis role was identified in P.insularum, using a genomics approach, to better understand its mechanism of action, and usefulness in its traditional use for reducing inflammation. Through fractionalization of the homogenate, the researchers were able to identify two flavanol glycosides, rutin and nicotiflorin, each which binded iron. Relating these findings to mammalian immune cells and their traditional action in the human body, researchers found that the iron-chelator activity of the P.insularum homogenate decreased pro-inflammatory responses in the body and enhanced anti-inflammatory cytokine responses within immune cells. Similarly, Ibuprofen chelates iron in a stable manner, enabling treatment of inflammation due to iron overload. Using metabolomics, a deeper understanding of Samoan traditional medicine and its parallels to western medicine can be used to advance pharmaceuticals as we know today.&nbsp; &nbsp

    The International Law of Colonialism in East Africa: Germany, England, and the Doctrine of Discovery

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    The non-European, non-Christian world was colonized under international law that is known today as the Doctrine of Discovery. This common-law international Doctrine was codified into European international law at the Berlin Conference of 1884–85 and in the Berlin Act of 1885 specifically to partition and colonize Africa. Thirteen European countries and the United States attended the four-month Conference, which ended with thirteen countries signing the Berlin Act on February 26, 1885. Under the Discovery Doctrine and the Berlin Act, these European countries claimed superior rights over African nations and Indigenous Peoples. European explorers planted crosses, signed hundreds of treaties, and raised flags in many parts of Africa to make legal claims of ownership and domination over the native nations and peoples, and their lands and assets. These claims were justified in the fifteenth and in the nineteenth centuries by racial, ethnocentric, and religious ideas about the alleged superiority of European Christian nations. This Article examines the application of the Doctrine and the Berlin Act by England and Germany in East Africa, which now comprises Kenya, Uganda, and Tanzania. This comparative law analysis demonstrates convincingly that the Berlin Act and these colonizing countries applied what we define as the ten elements of the Doctrine of Discovery. These elements had been developed and refined by European legal and political systems since the mid-1400s. Over 400 years later, the Berlin Conference of 1884–85 expressly and implicitly adopted and codified all ten elements to control the European partition and colonization of Africa. Germany and England used this international law to colonize East Africa. Needless to say, European domination, exploitation, and colonization seriously injured the human, property, sovereign, and self-determination rights of Indigenous nations and peoples. The effects of colonization are still felt today. The comparative legal analysis set out in this article sheds light on how law affected and directed African colonization. It also develops a better understanding of the international law of colonialism as well as its historical process and impacts. This Article concludes by explaining the crucial importance of this knowledge

    Transposon vector-mediated stable gene transfer for the accelerated establishment of recombinant mammalian cell pools allowing for high-yield production of biologics

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    Stable recombinant mammalian cells are of growing importance in pharmaceutical biotechnology production scenarios for biologics such as monoclonal antibodies, growth and blood factors, cytokines and subunit vaccines. However, the establishment of recombinant producer cells using classical stable transfection of plasmid DNA is hampered by low stable gene transfer efficiencies. Consequently, subsequent selection of transgenic cells and the screening of clonal cell populations are time- and thus cost-intensive. To overcome these limitations, expression cassettes were embedded into transposon-derived donor vectors. Upon the co-transfection with transposase-encoding constructs, elevated vector copy numbers stably integrated into the genomes of the host cells are readily achieved facilitating under stringent selection pressure the establishment of cell pools characterized by sustained and high-yield recombinant protein production. Here, we discuss some aspects of transposon vector technologies, which render these vectors promising candidates for their further utilization in the production of biologics

    Transgene Expression and Transposition Efficiency of Two-Component Sleeping Beauty Transposon Vector Systems Utilizing Plasmid or mRNA Encoding the Transposase

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    The use of two-component transposon plasmid vector systems, namely, a transposase construct and a donor vector carrying the gene of interest (GOI) can accelerate the development of recombinant cell lines. However, the undesired stable transfection of the transposase construct and the sustained expression of the enzyme can cause genetic instability due to the re-mobilization of the previously transposed donor vectors. Using a Sleeping Beauty-derived vector system, we established three recombinant cell pools and demonstrate stable integration of the transposase construct and sustained expression of the transposase over a period of 48 days. To provide an alternative approach, transcripts of the transposase gene were generated in vitro and co-transfected with donor vector plasmid at different ratios and mediating high GOI copy number integrations and expression levels. We anticipate that the use of transposase mRNA will foster further improvements in future cell line development processes
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