96 research outputs found

    Convexity in source separation: Models, geometry, and algorithms

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    Source separation or demixing is the process of extracting multiple components entangled within a signal. Contemporary signal processing presents a host of difficult source separation problems, from interference cancellation to background subtraction, blind deconvolution, and even dictionary learning. Despite the recent progress in each of these applications, advances in high-throughput sensor technology place demixing algorithms under pressure to accommodate extremely high-dimensional signals, separate an ever larger number of sources, and cope with more sophisticated signal and mixing models. These difficulties are exacerbated by the need for real-time action in automated decision-making systems. Recent advances in convex optimization provide a simple framework for efficiently solving numerous difficult demixing problems. This article provides an overview of the emerging field, explains the theory that governs the underlying procedures, and surveys algorithms that solve them efficiently. We aim to equip practitioners with a toolkit for constructing their own demixing algorithms that work, as well as concrete intuition for why they work

    Convergence analysis for sequential Monte Carlo receivers in communications applications

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    Recently, sequential Monte Carlo methods have been used in the telecommunications field, finding application in receiver design. Several properties of these receivers make their designs very attractive. These receivers do not require channel state information or training. Therefore, they are bandwidth efficient and no communication bandwidth needs to be wasted on training. The receivers are optimal in the sense that they achieve a minimum symbol error rate regardless of the noise distribution, nonlinearities in the system, or distribution of the transmitted symbol. Moreover, these receivers are capable of producing soft-information outputs, which enables the designer to utilize iterative receiver architectures for near-optimal performance. In this work we investigate the convergence properties of these algorithms when utilized in various types of receivers. We quantify the convergence rate. We describe how various parameters (e.g., noise power, channel fading rate, etc) and factors (e.g., state-space model mismatch) affect the convergence rate and point out the factors that should be improved first to gain speed and accuracy in the convergence

    WASP: Scalable Bayes via barycenters of subset posteriors

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    The promise of Bayesian methods for big data sets has not fully been realized due to the lack of scalable computational algorithms. For massive data, it is necessary to store and process subsets on different machines in a distributed manner. We propose a simple, general, and highly efficient approach, which first runs a posterior sampling algorithm in parallel on different machines for subsets of a large data set. To combine these subset posteriors, we calculate the Wasserstein barycenter via a highly efficient linear program. The resulting estimate for the Wasserstein posterior (WASP) has an atomic form, facilitating straightforward estimation of posterior summaries of functionals of interest. The WASP approach allows posterior sampling algorithms for smaller data sets to be trivially scaled to huge data. We provide theoretical justification in terms of posterior consistency and algorithm efficiency. Examples are provided in complex settings including Gaussian process regression and nonparametric Bayes mixture models

    Recent Developments in CRISPR/Cas9 Genome-Editing Technology Related to Plant Disease Resistance and Abiotic Stress Tolerance

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    The revolutionary CRISPR/Cas9 genome-editing technology has emerged as a powerful tool for plant improvement, offering unprecedented precision and efficiency in making targeted gene modifications. This powerful and practical approach to genome editing offers tremendous opportunities for crop improvement, surpassing the capabilities of conventional breeding techniques. This article provides an overview of recent advancements and challenges associated with the application of CRISPR/Cas9 in plant improvement. The potential of CRISPR/Cas9 in terms of developing crops with enhanced resistance to biotic and abiotic stresses is highlighted, with examples of genes edited to confer disease resistance, drought tolerance, salt tolerance, and cold tolerance. Here, we also discuss the importance of off-target effects and the efforts made to mitigate them, including the use of shorter single-guide RNAs and dual Cas9 nickases. Furthermore, alternative delivery methods, such as protein- and RNA-based approaches, are explored, and they could potentially avoid the integration of foreign DNA into the plant genome, thus alleviating concerns related to genetically modified organisms (GMOs). We emphasize the significance of CRISPR/Cas9 in accelerating crop breeding processes, reducing editing time and costs, and enabling the introduction of desired traits at the nucleotide level. As the field of genome editing continues to evolve, it is anticipated that CRISPR/Cas9 will remain a prominent tool for crop improvement, disease resistance, and adaptation to challenging environmental conditions

    Loss of heme oxygenase 2 causes reduced expression of genes in cardiac muscle development and contractility and leads to cardiomyopathy in mice

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    Obstructive sleep apnea (OSA) is a common breathing disorder that affects a significant portion of the adult population. In addition to causing excessive daytime sleepiness and neurocognitive effects, OSA is an independent risk factor for cardiovascular disease; however, the underlying mechanisms are not completely understood. Using exposure to intermittent hypoxia (IH) to mimic OSA, we have recently reported that mice exposed to IH exhibit endothelial cell (EC) activation, which is an early process preceding the development of cardiovascular disease. Although widely used, IH models have several limitations such as the severity of hypoxia, which does not occur in most patients with OSA. Recent studies reported that mice with deletion of hemeoxygenase 2 (Hmox2-/-), which plays a key role in oxygen sensing in the carotid body, exhibit spontaneous apneas during sleep and elevated levels of catecholamines. Here, using RNA-sequencing we investigated the transcriptomic changes in aortic ECs and heart tissue to understand the changes that occur in Hmox2-/- mice. In addition, we evaluated cardiac structure, function, and electrical properties by using echocardiogram and electrocardiogram in these mice. We found that Hmox2-/- mice exhibited aortic EC activation. Transcriptomic analysis in aortic ECs showed differentially expressed genes enriched in blood coagulation, cell adhesion, cellular respiration and cardiac muscle development and contraction. Similarly, transcriptomic analysis in heart tissue showed a differentially expressed gene set enriched in mitochondrial translation, oxidative phosphorylation and cardiac muscle development. Analysis of transcriptomic data from aortic ECs and heart tissue showed loss of Hmox2 gene might have common cellular network footprints on aortic endothelial cells and heart tissue. Echocardiographic evaluation showed that Hmox2-/- mice develop progressive dilated cardiomyopathy and conduction abnormalities compared to Hmox2+/+ mice. In conclusion, we found that Hmox2-/- mice, which spontaneously develop apneas exhibit EC activation and transcriptomic and functional changes consistent with heart failure

    Deciphering Drought Response Mechanisms: Transcriptomic Insights from Drought-Tolerant and Drought-Sensitive Wheat (Triticum aestivum L.) Cultivars

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    Drought stress poses a significant threat to wheat (Triticum aestivum L.) cultivation, necessitating an in-depth understanding of the molecular mechanisms underpinning drought response in both tolerant and sensitive varieties. In this study, 12 diverse bread wheat cultivars were evaluated for their drought stress responses, with particular emphasis on the contrasting performance of cultivars Atay 85 (sensitive), Gerek 79, and Mufitbey (tolerant). Transcriptomic analysis was performed on the root and leaf tissues of the aforementioned cultivars subjected to 4-hour and 8-hour drought stress and compared with controls. Differentially expressed genes (DEGs) were categorized based on their cellular component, molecular function, and biological function. Notably, there was greater gene expression variability in leaf tissues compared to root tissues. A noticeable trend of decreased gene expression was observed for cellular processes such as protein refolding and cellular metabolic processes like photorespiration as drought stress duration increased (8 hours) in the leaf tissues of drought-tolerant and sensitive cultivars. Metabolic processes related to gene expression were predominantly activated in response to 4-hour and 8-hour drought stress. The drought-tolerant cultivars exhibited increased expression levels of genes related to protein binding, metabolic processes, and cellular functions, indicating their ability to adapt better to drought stress compared to the drought-sensitive cultivar Atay 85. We detected more than 25 differentially expressed TFs in leaf tissues under 4-hour and 8-hour drought stress, while only 4 TFs were identified in the root tissues of sensitive cultivar. In contrast, the tolerant cultivar exhibited more than 80 different TF transcripts in both leaves and roots after 4 hours of drought stress, with this number decreasing to 18 after 8 hours of drought stress. Differentially expressed genes with a focus on metal ion binding, carbohydrate degradation, ABA-related genes, and cell wall-related genes were highlighted. Ferritin (TaFer), TaPME42 and Extensin-like protein (TaExLP), Germin-like protein (TaGLP 9-1), Metacaspase-5 (TaMC5), Arogenate Dehydratase 5 (ADT-5), Phosphoglycerate/ bisphosphoglycerate mutase (TaPGM), Serine/threonine protein phosphatase 2A (TaPP2A), GIGANTEA (TaGI), Polyadenylate-binding protein (TaRBP45B) exhibited differential expression by qRT-PCR in root and leaf tissues of tolerant and sensitive bread wheat cultivars. This study provides valuable insights into the complex molecular mechanisms associated with drought response in wheat, highlighting genes and pathways involved in drought tolerance. Understanding these mechanisms is essential for developing drought-tolerant wheat varieties, enhancing agricultural sustainability, and addressing the challenges posed by water scarcity

    Synchronization of Circadian Clock Gene Expression in Arabidopsis and Hyaloperonospora arabidopsidis and its Impact on Host-Pathogen Interactions

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    Organisms across all kingdoms have an internal circadian clock running in 24h cycles. This clock affects a variety of processes, including innate immunity in plants. However, the role of pathogen circadian clocks had not been extensively explored. We previously showed that light can influence infection of the oomycete Hyaloperonospora arabidopsidis (Hpa, downy mildew disease) on its natural host Arabidopsis thaliana. Here, we identified Hpa orthologs of known circadian clock genes (CCGs) Drosophila TIMELESS (TIM) and Arabidopsis Sensitive to Red Light Reduced 1 (AtSRR1) genes. Expression of both HpaTIM and HpaSRR1 showed a circadian rhythm when Hpa was exposed to constant light. Contrastingly, these two genes were negatively regulated by constant dark exposure. Furthermore, the expression patterns of HpaTIM and HpaSRR1 correlate with those of AtCCA1 and AtLHY, indicating a synchronisation of biological clock genes between the host and the pathogen. In addition, screening mutants of Arabidopsis Clock Regulated Genes (AtCRGs) with three virulent Hpa isolates revealed that mutations in AtCRGs influenced HpaTIM and HpaSRR1 expression and Hpa development, indicating a functional link between the plant biological clock and virulence. Moreover, sporulation of Hpa was reduced by targeting HpaTIM and HpaSRR1 with short synthesized small interfering RNAs, indicating that the pathogen clock is also relevant to virulence. We propose that plant and pathogen clocks are synchronized during infection and that proper regulation of both clocks are genetically necessary for pathogen virulence

    Human MLH1 deficiency predisposes to hematological malignancy and neurofibromatosis type 1

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    Heterozygous germ-line mutations in the DNA mismatch repair genes lead to hereditary nonpolyposis colorectal cancer. The disease susceptibility of individuals who constitutionally lack both wild-type alleles is unknown. We have identified three offspring in a hereditary nonpolyposis colorectal cancer family who developed hematological malignancy at a very early age, and at least two of them displayed signs of neurofibromatosis type 1 (NF1). DNA sequence analysis and allele-specific amplification in two siblings revealed a homozygous MLH1 mutation (C676T → Arg226Stop). Thus, a homozygous germ- line MLH1 mutation and consequent mismatch repair deficiency results in a mutator phenotype characterized by leukemia and/or lymphoma associated with neurofibromatosis type 1

    Enhancement of immune response of HBsAg loaded poly(L-lactic acid) microspheres against Hepatitis B through incorporation of alum and chitosan

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    Purpose: Poly (L-lactic acid) (PLA) microparticles encapsulating Hepatitis B surface antigen (HBsAg) with alum and chitosan were investigated for their potential as a vaccine delivery system. Methods: The microparticles, prepared using a water-in-oil-in-water (w/o/w) double emulsion solvent evaporation method with polyvinyl alcohol (PVA) or chitosan as the external phase stabilising agent showed a significant increase in the encapsulation efficiency of the antigen. Results: PLA-Alum and PLA-chitosan microparticles induced HBsAg serum specific IgG antibody responses significantly higher than PLA only microparticles and free antigen following subcutaneous administration. Chitosan not only imparted a positive charge to the surface of the microparticles but was also able to increase the serum specific IgG antibody responses significantly. Conclusions: The cytokine assays showed that the serum IgG antibody response induced is different according to the formulation, indicated by the differential levels of interleukin 4 (IL-4), interleukin 6 (IL-6) and interferon gamma (IFN-Îł). The microparticles eliciting the highest IgG antibody response did not necessarily elicit the highest levels of the cytokines IL-4, IL-6 and IFN-Îł

    Examining the Heterogeneous Genome Content of Multipartite Viruses BMV and CCMV by Native Mass Spectrometry

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    Since the concept was first introduced by Brian Chait and co-workers in 1991, mass spectrometry of proteins and protein complexes under non-denaturing conditions (native MS) has strongly developed, through parallel advances in instrumentation, sample preparation, and data analysis tools. However, the success rate of native MS analysis, particularly in heterogeneous mega-Dalton (MDa) protein complexes, still strongly depends on careful instrument modification. Here, we further explore these boundaries in native mass spectrometry, analyzing two related endogenous multipartite viruses: the Brome Mosaic Virus (BMV) and the Cowpea Chlorotic Mottle Virus (CCMV). Both CCMV and BMV are approximately 4.6 megadalton (MDa) in mass, of which approximately 1 MDA originates from the genomic content of the virion. Both viruses are produced as mixtures of three particles carrying different segments of the genome, varying by approximately 0.1 MDA in mass (~2%). This mixture of particles poses a challenging analytical problem for high-resolution native MS analysis, given the large mass scales involved. We attempt to unravel the particle heterogeneity using both Q-TOF and Orbitrap mass spectrometers extensively modified for analysis of very large assemblies. We show that manipulation of the charging behavior can provide assistance in assigning the correct charge states. Despite their challenging size and heterogeneity, we obtained native mass spectra with resolved series of charge states for both BMV and CCMV, demonstrating that native MS of endogenous multipartite virions is feasible. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s13361-016-1348-6) contains supplementary material, which is available to authorized users
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