751 research outputs found

    Using Column Generation to Solve Extensions to the Markowitz Model

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    We introduce a solution scheme for portfolio optimization problems with cardinality constraints. Typical portfolio optimization problems are extensions of the classical Markowitz mean-variance portfolio optimization model. We solve such type of problems using a method similar to column generation. In this scheme, the original problem is restricted to a subset of the assets resulting in a master convex quadratic problem. Then the dual information of the master problem is used in a sub-problem to propose more assets to consider. We also consider other extensions to the Markowitz model to diversify the portfolio selection within the given intervals for active weights.Comment: 16 pages, 3 figures, 2 tables, 1 pseudocod

    Serotype 1 pneumococcus: epidemiology, genomics, and disease mechanisms

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    Streptococcus pneumoniae (the 'pneumococcus') is a significant cause of morbidity and mortality worldwide, causing life-threatening diseases such as pneumonia, bacteraemia, and meningitis, with an annual death burden of over one million. Discovered over a century ago, pneumococcal serotype 1 (S1) is a significant cause of these life-threatening diseases. Our understanding of the epidemiology and biology of pneumococcal S1 has significantly improved over the past two decades, informing the development of preventative and surveillance strategies. However, many questions remain unanswered. Here, we review the current state of knowledge of pneumococcal S1, with a special emphasis on clinical epidemiology, genomics, and disease mechanisms

    Increased pathogenicity of pneumococcal serotype 1 is driven by rapid autolysis and release of pneumolysin

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    Streptococcus pneumoniae serotype 1 is the predominant cause of invasive pneumococcal disease in sub-Saharan Africa, but the mechanism behind its increased invasiveness is not well understood. Here, we use mouse models of lung infection to identify virulence factors associated with severe bacteraemic pneumonia during serotype-1 (ST217) infection. We use BALB/c mice, which are highly resistant to pneumococcal pneumonia when infected with other serotypes. However, we observe 100% mortality and high levels of bacteraemia within 24 hours when BALB/c mice are intranasally infected with ST217. Serotype 1 produces large quantities of pneumolysin, which is rapidly released due to high levels of bacterial autolysis. This leads to substantial levels of cellular cytotoxicity and breakdown of tight junctions between cells, allowing a route for rapid bacterial dissemination from the respiratory tract into the blood. Thus, our results offer an explanation for the increased invasiveness of serotype 1

    A computational analysis of Turkish makam music based on a probabilistic characterization of segmented phrases

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    This study targets automatic analysis of Turkish makam music pieces on the phrase level. While makam is most simply defined as an organization of melodic phrases, there has been very little effort to computationally study melodic structure in makam music pieces. In this work, we propose an automatic analysis algorithm that takes as input symbolic data in the form of machine-readable scores that are segmented into phrases. Using a measure of makam membership for phrases, our method outputs for each phrase the most likely makam the phrase comes from. The proposed makam membership definition is based on Bayesian classification and the algorithm is specifically designed to process the data with overlapping classes. The proposed analysis system is trained and tested on a large data set of phrases obtained by transferring phrase boundaries manually written by experts of makam music on printed scores, to machine-readable data. For the task of classifying all phrases, or only the beginning phrases to come from the main makam of the piece, the corresponding F-measures are.52 and.60 respectively.Scientific and Technological Research Council of Turkey, TUBITAK (112E162

    Design & investigation of 10x10 gbit/s MDM over hybrid FSO link under different weather conditions and fiber to the home

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    In this paper, we design and investigate 10-channels of mode division multiplexer (MDM) over hybrid free-space optics (FSO) link in several weather conditions to achieve the maximum possible medium range and fiber to the home (FTTH) for high bandwidth access networks. System capacity can be effectively increased with the use of MDM over hybrid FSO-FTTH. In this study, a 10-channel MDM over FSO-FTTH system has been analyzed in different weather conditions that operate at 1550 nm wavelength. The simulated system has transmitted 100 Gbit/s up for a distance of 3200 meters FSO in superbly clear weather condition. It also transmitted 100 Gbit/s up for a distance of 650 meters FSO during heavy rain. The validation of this study is measures based on eye diagrams bit-error rates (BER) that have been analyzed

    Influence of Streptococcus pneumoniae Within-Strain Population Diversity on Virulence and Pathogenesis

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    The short generation time of many bacterial pathogens allows the accumulation of de novo mutations during routine culture procedures used for the preparation and propagation of bacterial stocks. Taking the major human pathogen Streptococcus pneumoniae as an example, we sought to determine the influence of standard laboratory handling of microbes on within-strain genetic diversity and explore how these changes influence virulence characteristics and experimental outcomes. A single culture of S. pneumoniae D39 grown overnight resulted in the enrichment of previously rare genotypes present in bacterial freezer stocks and the introduction of new variation to the bacterial population through the acquisition of mutations. A comparison of D39 stocks from different laboratories demonstrated how changes in bacterial population structure taking place during individual culture events can cumulatively lead to fixed, divergent change that profoundly alters virulence characteristics. The passage of D39 through mouse models of infection, a process used to standardize virulence, resulted in the enrichment of high-fitness genotypes that were originally rare (,2% frequency) in D39 culture collection stocks and the loss of previously dominant genotypes. In the most striking example, the selection of a,2%-frequency genotype carrying a mutation in sdhB, a gene thought to be essential for the establishment of lung infection, was associated with enhanced systemic virulence. Three separately passaged D39 cultures originating from the same frozen stocks showed considerable genetic divergence despite comparable virulence. IMPORTANCE: Laboratory bacteriology involves the use of high-density cultures that we often assume to be clonal but that in reality are populations consisting of multiple genotypes at various abundances. We have demonstrated that the genetic structure of a single population of a widely used Streptococcus pneumoniae strain can be substantially altered by even short-term laboratory handling and culture and that, over time, this can lead to changes in virulence characteristics. Our findings suggest that caution should be applied when comparing data generated in different laboratories using the same strain but also when comparing data within laboratories over time. Given the dramatic reductions in the cost of next-generation sequencing technology in recent years, we advocate for the frequent sampling and sequencing of bacterial isolate collections
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