147 research outputs found

    On the Cauchy problem for a semilinear fractional elliptic equation

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    We study, for the first time in the literature on the subject, the Cauchy problem for a semilinear fractional elliptic equation. Under an a priori assumption on the solution, we propose the Fourier truncation method for stabilizing the ill-posed problem. A stability estimate of logarithmic type is established

    Relationship Between Obesity and Diabetes in a US Adult Population: Findings from the National Health and Nutrition Examination Survey, 1999–2006

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    # The Author(s) 2010. This article is published with open access at Springerlink.com Background Obesity is one of the most important modifiable risk factors for the prevention of type 2 diabetes. The aim of this study was to examine the prevalence of diabetes with increasing severity of obesity and the distribution of HbA1c levels in diabetics participating in the latest National Health and Nutrition Examination Survey (NHANES). Methods Data from a representative sample of adults with diabetes participating in the NHANES between 1999 and 2006 were reviewed. The prevalence of diabetes and levels of fasting glucose, insulin, c-peptide, and HbA1c were examined across different weight classes with normal weight, overweight, and obesity classes 1, 2, and 3 were defined as body mass index (BMI) of <25.0, 25.0–29.9, 30.0–34.9, 35.0–39.9, and equal to 40.0, respectively. The distribution of HbA1c levels among adults with diabetes was also examined. Results There were 2,894 adults with diabetes (13.6%) among the 21,205 surveyed participants. Among the adults with diabetes, the mean age was 59 years, the mean fasting glucose was 155±2 mg/dl, and the mean HbA1c was 7.2%; 80.3 % of diabetics were considered overweight (BMI≥25) and 49.1 % of diabetics were considered obese (BMI≥30). Presented as a poster presentation at the American Society fo

    Blocking tumor-educated MSC paracrine activity halts osteosarcoma progression

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    Purpose: Human osteosarcoma is a genetically heterogeneous bone malignancy with poor prognosis despite the employment of aggressive chemotherapy regimens. Because druggable driver mutations have not been established, dissecting the interactions between osteosarcoma cells and supporting stroma may provide insights into novel therapeutic targets.Experimental Design: By using a bioluminescent orthotopic xenograft mouse model of osteosarcoma, we evaluated the effect of tumor extracellular vesicle (EV)-educated mesenchymal stem cells (TEMSC) on osteosarcoma progression. Characterization and functional studies were designed to assess the mechanisms underlying MSC education. Independent series of tissue specimens were analyzed to corroborate the preclinical findings, and the composition of patient serum EVs was analyzed after isolation with size-exclusion chromatography.Results: We show that EVs secreted by highly malignant osteosarcoma cells selectively incorporate a membrane-associated form of TGFβ, which induces proinflammatory IL6 production by MSCs. TEMSCs promote tumor growth, accompanied with intratumor STAT3 activation and lung metastasis formation, which was not observed with control MSCs. Importantly, intravenous administration of the anti-IL6 receptor antibody tocilizumab abrogated the tumor-promoting effects of TEMSCs. RNA-seq analysis of human osteosarcoma tissues revealed a distinct TGFβ-induced prometastatic gene signature. Tissue microarray immunostaining indicated active STAT3 signaling in human osteosarcoma, consistent with the observations in TEMSC-treated mice. Finally, we isolated pure populations of EVs from serum and demonstrated that circulating levels of EV-associated TGFβ are increased in osteosarcoma patients.Conclusions: Collectively, our findings suggest that TEMSCs promote osteosarcoma progression and provide the basis for testing IL6- and TGFβ-blocking agents as new therapeutic options for osteosarcoma patients

    Statistical significance of cis-regulatory modules

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    BACKGROUND: It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. RESULTS: We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. CONCLUSION: The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM) and MODSTORM software

    SC-FDMA-based resource allocation and power control scheme for D2D communication using LTE-A uplink resource

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    Device-to-device (D2D) communication-enabled cellular networks allow cellular devices to directly communicate with each other without any evolved NodeB (eNB). D2D communication aims to improve the spectral efficiency and increases the overall system capacity. For future mobile networks, intelligent radio resource allocation and power control schemes are required to accommodate the increasing number of cellular devices and their growing demand of data traffic. In this paper, a combined resource allocation and power control scheme for D2D communication is proposed. In the proposed scheme, D2D communication reuses the uplink (UL) resources of conventional cellular user equipments (CUEs); therefore, we have adopted single-carrier frequency division multiple access (SC-FDMA) as UL transmission scheme. The proposed scheme uses fractional frequency reuse (FFR)-based architecture to efficiently allocate the resources and mitigate the interference between CUEs and D2D user equipments (DUEs). In order to guarantee the user fairness, the proposed scheme uses the well-known proportional fair (PF) scheduling algorithm for resource allocation. We have also proposed an intelligent power control scheme which provides equal opportunity to both CUEs and DUEs to achieve a certain minimum signal-to-interference and noise ratio (SINR) value. The performance evaluation results show that the proposed scheme significantly improves the overall cell capacity and achieves low peak-to-average power ratio (PAPR)

    Complete Sequencing and Pan-Genomic Analysis of Lactobacillus delbrueckii subsp. bulgaricus Reveal Its Genetic Basis for Industrial Yogurt Production

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    Lactobacillus delbrueckii subsp. bulgaricus (Lb. bulgaricus) is an important species of Lactic Acid Bacteria (LAB) used for cheese and yogurt fermentation. The genome of Lb. bulgaricus 2038, an industrial strain mainly used for yogurt production, was completely sequenced and compared against the other two ATCC collection strains of the same subspecies. Specific physiological properties of strain 2038, such as lysine biosynthesis, formate production, aspartate-related carbon-skeleton intermediate metabolism, unique EPS synthesis and efficient DNA restriction/modification systems, are all different from those of the collection strains that might benefit the industrial production of yogurt. Other common features shared by Lb. bulgaricus strains, such as efficient protocooperation with Streptococcus thermophilus and lactate production as well as well-equipped stress tolerance mechanisms may account for it being selected originally for yogurt fermentation industry. Multiple lines of evidence suggested that Lb. bulgaricus 2038 was genetically closer to the common ancestor of the subspecies than the other two sequenced collection strains, probably due to a strict industrial maintenance process for strain 2038 that might have halted its genome decay and sustained a gene network suitable for large scale yogurt production

    Gata3 Acts Downstream of β-Catenin Signaling to Prevent Ectopic Metanephric Kidney Induction

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    Metanephric kidney induction critically depends on mesenchymal–epithelial interactions in the caudal region of the nephric (or Wolffian) duct. Central to this process, GDNF secreted from the metanephric mesenchyme induces ureter budding by activating the Ret receptor expressed in the nephric duct epithelium. A failure to regulate this pathway is believed to be responsible for a large proportion of the developmental anomalies affecting the urogenital system. Here, we show that the nephric duct-specific inactivation of the transcription factor gene Gata3 leads to massive ectopic ureter budding. This results in a spectrum of urogenital malformations including kidney adysplasia, duplex systems, and hydroureter, as well as vas deferens hyperplasia and uterine agenesis. The variability of developmental defects is reminiscent of the congenital anomalies of the kidney and urinary tract (CAKUT) observed in human. We show that Gata3 inactivation causes premature nephric duct cell differentiation and loss of Ret receptor gene expression. These changes ultimately affect nephric duct epithelium homeostasis, leading to ectopic budding of interspersed cells still expressing the Ret receptor. Importantly, the formation of these ectopic buds requires both GDNF/Ret and Fgf signaling activities. We further identify Gata3 as a central mediator of β-catenin function in the nephric duct and demonstrate that the β-catenin/Gata3 pathway prevents premature cell differentiation independently of its role in regulating Ret expression. Together, these results establish a genetic cascade in which Gata3 acts downstream of β-catenin, but upstream of Ret, to prevent ectopic ureter budding and premature cell differentiation in the nephric duct

    Erratum to: Scaling up strategies of the chronic respiratory disease programme of the European Innovation Partnership on Active and Healthy Ageing (Action Plan B3: Area 5).

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    [This corrects the article DOI: 10.1186/s13601-016-0116-9.]
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