73 research outputs found

    Service Bundling and the Role of Access Charge in the Broadband Internet Service Market

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    Using the classical Hotelling model, this paper analyzes the incentive for a CATV service provider to bundle broadband internet services when entering the broadband internet services market. In addition, the effect of such service bundling by an entrant on the market incumbent with ownership over existing bottleneck facilities is analyzed. Furthermore, an access charge that maximizes social welfare is explored and determined. Two cases are considered: in the first case, the market is fully covered; and in the second case, the market is not fully covered. With full market coverage, an entrant has an incentive for service bundling if there is sufficient service differentiation. The entrant's bundling strategy reduces the incumbent's profit. In this case, the total social welfare is independent of the level of the access charge and only has an effect of redistributing the net surplus between consumers and the incumbent. With partial market coverage, the entrant has an incentive for service bundling at a low access charge. The incumbent's profit increases if the access charge is higher than the cost of access provisioning. In this case, the total social welfare is dependent on the level of access charge and the welfare maximizing access charge is less than the unit cost of providing access.cable TV; broadband internet service; bundling; access charge; convergence

    Bayesian Modeling Approaches for Temporal Dynamics in RNA-seq Data

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    Analysis of differential expression has been a central role to address the variety of biological questions in the manner to characterize abnormal patterns of cellular and molecular functions for last decades. To date, identification of differentially expressed genes and isoforms has been more intensively focused on temporal dynamics over a series of time points. Bayesian strategies have been successfully employed to uncover the complexity of biological interest with the methodological and analytical perspectives for the various platforms of high-throughput data, for instance, methods in differential expression analysis and network modules in transcriptome data, peak-callers in ChipSeq data, target prediction in microRNA data and meta-methods between different platforms. In this chapter, we will discuss how our methodological works based on Bayesian models address important questions to arise in the architecture of temporal dynamics in RNA-seq data

    Effects of missing value imputation on down-stream analyses in microarray data

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    Amongst the high-throughput technologies, DNA microarray experiments provide enormous quantity of genes and arrays with biological information to disease. The studies of gene expression values in various conditions and various organisms in public health have led to the identification of genes to the comparison between tumor and normal, clinically relevant subtypes of tumor, and prognostic signatures and have ultimately provided the potential targets for specific therapy of public health disease. Despite such advances and the popular usage of microarray, the microarray experiments frequently produce multiple missing values due to many flaw factors such as dust, scratches on the slides, insufficient resolution, or hybridization errors on the chips. Thus, gene expression data contains missing entries and a large number of genes may be affected. Unfortunately, many downstream algorithms for gene expression analysis require a complete matrix as an input. Therefore effective missing value imputation methods are needed and have been developed in the literature so far. There exists no uniformly superior imputation method and the performance depends on the structure and nature of a data set. In addition, imputation methods have been mostly compared in terms of variants of RMSEs (Root Mean Squared Error) to compare similarity between true expression values and imputed expression values. The drawback of RMSE-based evaluation is that the measure does not reflect the true biological effect in down-stream analyses. In this dissertation, we will investigate how missing value imputation process affects the biological result of differentially expressed genes discovery, clustering and classification. Multiple statistical methods in each of the downstream analysis will be considered. Quantitative measures reflecting the true biological effects in each down-stream analysis will be used to evaluate imputation methods and be compared to RMSE-based evaluation

    Pediatric asthma and autism-genomic perspectives.

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    High-throughput technologies, ranging from microarrays to NexGen sequencing of RNA and genomic DNA, have opened new avenues for exploration of the pathobiology of human disease. Comparisons of the architecture of the genome, identification of mutated or modified sequences, and pre-and post- transcriptional regulation of gene expression as disease specific biomarkers are revolutionizing our understanding of the causes of disease and are guiding the development of new therapies. There is enormous heterogeneity in types of genomic variation that occur in human disease. Some are inherited, while others are the result of new somatic or germline mutations or errors in chromosomal replication. In this review, we provide examples of changes that occur in the human genome in two of the most common chronic pediatric disorders, autism and asthma. The incidence and economic burden of both of these disorders are increasing worldwide. Genomic variations have the potential to serve as biomarkers for personalization of therapy and prediction of outcomes

    Service Bundling and the Role of Access Charge in the Broadband Internet Service Market

    Get PDF
    Using the classical Hotelling model, this paper analyzes the incentive for a CATV service provider to bundle broadband internet services when entering the broadband internet services market. In addition, the effect of such service bundling by an entrant on the market incumbent with ownership over existing bottleneck facilities is analyzed. Furthermore, an access charge that maximizes social welfare is explored and determined. Two cases are considered: in the first case, the market is fully covered; and in the second case, the market is not fully covered. With full market coverage, an entrant has an incentive for service bundling if there is sufficient service differentiation. The entrant's bundling strategy reduces the incumbent's profit. In this case, the total social welfare is independent of the level of the access charge and only has an effect of redistributing the net surplus between consumers and the incumbent. With partial market coverage, the entrant has an incentive for service bundling at a low access charge. The incumbent's profit increases if the access charge is higher than the cost of access provisioning. In this case, the total social welfare is dependent on the level of access charge and the welfare maximizing access charge is less than the unit cost of providing access

    3′ Splice Site Sequences of Spinal Muscular Atrophy Related SMN2 Pre-mRNA Include Enhancers for Nearby Exons

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    Spinal muscular atrophy (SMA) is a human genetic disease which occurs because of the deletion or mutation of SMN1 gene. SMN1 gene encodes the SMN protein which plays a key role in spliceosome assembly. Although human patients contain SMN2, a duplicate of SMN1, splicing of SMN2 produces predominantly exon 7 skipped isoform. In order to understand the functions of splice site sequences on exon 7 and 8, we analyzed the effects of conserved splice site sequences on exon 7 skipping of SMN2 and SMN1 pre-mRNA. We show here that conserved 5′ splice site sequence of exon 7 promoted splicing of nearby exons and subsequently reduced splicing of distant exons. However, to our surprise, conserved 3′ splice site sequence of exon 7 and 8 did not promote splicing of nearby exons. By contrast, the mutation inhibited splicing of nearby exons and subsequently promoted splicing of distant exons. Our study shows that 3′ splice sites of exon 7 and 8 contain enhancer for their splice site selection, in addition to providing cleavage sites

    Chaperone-like protein DAY plays critical roles in photomorphogenesis.

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    Photomorphogenesis, light-mediated development, is an essential feature of all terrestrial plants. While chloroplast development and brassinosteroid (BR) signaling are known players in photomorphogenesis, proteins that regulate both pathways have yet to be identified. Here we report that DE-ETIOLATION IN THE DARK AND YELLOWING IN THE LIGHT (DAY), a membrane protein containing DnaJ-like domain, plays a dual-role in photomorphogenesis by stabilizing the BR receptor, BRI1, as well as a key enzyme in chlorophyll biosynthesis, POR. DAY localizes to both the endomembrane and chloroplasts via its first transmembrane domain and chloroplast transit peptide, respectively, and interacts with BRI1 and POR in their respective subcellular compartments. Using genetic analysis, we show that DAY acts independently on BR signaling and chlorophyll biogenesis. Collectively, this work uncovers DAY as a factor that simultaneously regulates BR signaling and chloroplast development, revealing a key regulator of photomorphogenesis that acts across cell compartments

    Cutoff Values of Surrogate Measures of Insulin Resistance for Metabolic Syndrome in Korean Non-diabetic Adults

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    We investigated the cutoff values of surrogate of insulin resistance for diagnosing metabolic syndrome in Korean adults. The data from 976 non-diabetic individuals (484 men and 492 women) aged 30-79 yr were analyzed. We determined the odds ratios for the prevalence of metabolic syndrome according to the quartiles of fasting insulin, homeostasis model for insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) as independent variables, while adjusting for age, sex, and body mass index. The cutoff values of fasting insulin, HOMA-IR, and QUICKI were estimated by the areas under the receiver-operating characteristic (ROC) curves. The cutoff points for defining insulin resistance are a fasting insulin level of 12.94 µU/mL, HOMA-IR=3.04 as the 75th percentile value, and QUICKI=0.32 as the 25th percentile value. Compared with the lowest quartile, the adjusted odds ratios for the prevalence of metabolic syndrome in the highest quartiles of fasting insulin, HOMA-IR, and QUICKI were 1.95 (1.26-3.01), 2.27 (1.45-3.56), and 2.27 (1.45-3.56), respectively. The respective cutoff values for fasting serum insulin, HOMA-IR, and QUICKI by ROC analysis were 10.57 µU/mL (sensitivity 58.5%, specificity 66.8%), 2.34 (sensitivity 62.8%, specificity 65.7%), and 0.33 (sensitivity 61.2%, specificity 66.8%). Fasting insulin, HOMA-IR, and QUICKI can be used as surrogate measures of insulin resistance in Korean non-diabetic adults

    Pediatric asthma and autism—genomic perspectives

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