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Sample records for agilent human mirna

  1. Human factors in agile manufacturing

    SciTech Connect

    Forsythe, C.

    1995-03-01

    As industries position themselves for the competitive markets of today, and the increasingly competitive global markets of the 21st century, agility, or the ability to rapidly develop and produce new products, represents a common trend. Agility manifests itself in many different forms, with the agile manufacturing paradigm proposed by the Iacocca Institute offering a generally accepted, long-term vision. In its many forms, common elements of agility or agile manufacturing include: changes in business, engineering and production practices, seamless information flow from design through production, integration of computer and information technologies into all facets of the product development and production process, application of communications technologies to enable collaborative work between geographically dispersed product development team members and introduction of flexible automation of production processes. Industry has rarely experienced as dramatic an infusion of new technologies or as extensive a change in culture and work practices. Human factors will not only play a vital role in accomplishing the technical and social objectives of agile manufacturing. but has an opportunity to participate in shaping the evolution of industry paradigms for the 21st century.

  2. Agile

    NASA Technical Reports Server (NTRS)

    Trimble, Jay Phillip

    2013-01-01

    This is based on a previous talk on agile development. Methods for delivering software on a short cycle are described, including interactions with the customer, the affect on the team, and how to be more effective, streamlined and efficient.

  3. Expression Profiles of miRNA Subsets Distinguish Human Colorectal Carcinoma and Normal Colonic Mucosa

    PubMed Central

    Pellatt, Daniel F; Stevens, John R; Wolff, Roger K; Mullany, Lila E; Herrick, Jennifer S; Samowitz, Wade; Slattery, Martha L

    2016-01-01

    OBJECTIVES: MicroRNAs (miRNAs) are small, non-protein-coding RNA molecules that are commonly dysregulated in colorectal tumors. The objective of this study was to identify smaller subsets of highly predictive miRNAs. METHODS: Data come from population-based studies of colorectal cancer conducted in Utah and the Kaiser Permanente Medical Care Program. Tissue samples were available for 1,953 individuals, of which 1,894 had carcinoma tissue and 1,599 had normal mucosa available for statistical analysis. Agilent Human miRNA Microarray V.19.0 was used to generate miRNA expression profiles; validation of expression levels was carried out using quantitative PCR. We used random forest analysis and verified findings with logistic modeling in separate data sets. Important microRNAs are identified and bioinformatics tools are used to identify target genes and related biological pathways. RESULTS: We identified 16 miRNAs for colon and 17 miRNAs for rectal carcinoma that appear to differentiate between carcinoma and normal mucosa; of these, 12 were important for both colon and rectal cancer, hsa-miR-663b, hsa-miR-4539, hsa-miR-17-5p, hsa-miR-20a-5p, hsa-miR-21-5p, hsa-miR-4506, hsa-miR-92a-3p, hsa-miR-93-5p, hsa-miR-145-5p, hsa-miR-3651, hsa-miR-378a-3p, and hsa-miR-378i. Estimated misclassification rates were low at 4.83% and 2.5% among colon and rectal observations, respectively. Among independent observations, logistic modeling reinforced the importance of these miRNAs, finding the primary principal components of their variation statistically significant (P<0.001 among both colon and rectal observations) and again producing low misclassification rates. Repeating our analysis without those miRNAs initially identified as important identified other important miRNAs; however, misclassification rates increased and distinctions between remaining miRNAs in terms of classification importance were reduced. CONCLUSIONS: Our data support the hypothesis that while many miRNAs are

  4. miRNAs in human cancer

    PubMed Central

    Farazi, Thalia A.; Spitzer, Jessica I.; Morozov, Pavel; Tuschl, Thomas

    2010-01-01

    Mature microRNAs (miRNAs) are single-stranded RNA molecules of 20- to 23-nucleotide (nt) length that control gene expression in many cellular processes. These molecules typically reduce the stability of mRNAs, including those of genes that mediate processes in tumorigenesis, such as inflammation, cell cycle regulation, stress response, differentiation, apoptosis, and invasion. miRNA targeting is mostly achieved through specific base-pairing interactions between the 5′ end (“seed” region) of the miRNA and sites within coding and untranslated regions (UTRs) of mRNAs; target sites in the 3′ UTR lead to more effective mRNA destabilization. Since miRNAs frequently target hundreds of mRNAs, miRNA regulatory pathways are complex. To provide a critical overview of miRNA dysregulation in cancer we first discuss the methods currently available for studying the role of miRNAs in cancer and then review miRNA genomic organization, biogenesis, and mechanism of target recognition examining how these processes are altered in tumorigenesis. Given the critical role miRNAs play in tumorigenesis processes and their disease specific expression, they hold potential as therapeutic targets and novel biomarkers. PMID:21125669

  5. Distribution of miRNA expression across human tissues.

    PubMed

    Ludwig, Nicole; Leidinger, Petra; Becker, Kurt; Backes, Christina; Fehlmann, Tobias; Pallasch, Christian; Rheinheimer, Steffi; Meder, Benjamin; Stähler, Cord; Meese, Eckart; Keller, Andreas

    2016-05-05

    We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10(-8)) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas).

  6. miRNA Expression in Pediatric Failing Human Heart

    PubMed Central

    Stauffer, Brian L.; Russell, Gloria; Nunley, Karin; Miyamoto, Shelley D.; Sucharov, Carmen C.

    2013-01-01

    miRNAs are short regulatory RNAs that can regulate gene expression through interacting with the 3'UTR of target mRNAs. Although the role of miRNAs has been extensively studied in adult human and animal models of heart disease, nothing is known about their expression in pediatric heart failure patients. Different than adults with heart failure, pediatric patients respond well to phosphodiesterase inhibitor (PDEi) treatment, which is safe in the outpatient setting, results in fewer heart failure emergency department visits, fewer cardiac hospital admissions and improved NYHA classification. We have recently shown that the pediatric heart failure patients display a unique molecular profile that is different from adults with heart failure. In this study we show for the first time that pediatric heart failure patients display a unique miRNA profile, and that expression of some miRNAs correlate with response to PDEi treatment. Moreover, we show that expression of Smad4, a potential target for PDEi-regulated miRNAs, is normalized in PDEi-treated patients. Since miRNAs may be used as therapy for human heart failure, our results underscore the importance of defining the molecular characteristics of pediatric heart failure patients, so age-appropriate therapy can be designed for this population. PMID:23333438

  7. Identifying miRNA synergistic regulatory networks in heterogeneous human data via network motifs.

    PubMed

    Zhang, Junpeng; Duy Le, Thuc; Liu, Lin; He, Jianfeng; Li, Jiuyong

    2016-02-01

    Understanding the synergism of multiple microRNAs (miRNAs) in gene regulation can provide important insights into the mechanisms of complex human diseases caused by miRNA regulation. Therefore, it is important to identify miRNA synergism and study miRNA characteristics in miRNA synergistic regulatory networks. A number of methods have been proposed to identify miRNA synergism. However, most of the methods only use downstream target genes of miRNAs to infer miRNA synergism when miRNAs can also be regulated by upstream transcription factors (TFs) at the transcriptional level. Additionally, most methods are based on statistical associations identified from data without considering the causal nature of gene regulation. In this paper, we present a causality based framework, called mirSRN (miRNA synergistic regulatory network), to infer miRNA synergism in human molecular systems by considering both downstream miRNA targets and upstream TF regulation. We apply the proposed framework to two real world datasets and discover that almost all the top 10 miRNAs with the largest node degree in the mirSRNs are associated with different human diseases, including cancer, and that the mirSRNs are approximately scale-free and small-world networks. We also find that most miRNAs in the networks are frequently synergistic with other miRNAs, and miRNAs related to the same disease are likely to be synergistic and in a cluster linked to a biological function. Synergistic miRNA pairs show higher co-expression level, and may have potential functional relationships indicating collaboration between the miRNAs. Functional validation of the identified synergistic miRNAs demonstrates that these miRNAs cause different kinds of diseases. These results deepen our understanding of the biological meaning of miRNA synergism.

  8. Deregulation of the miRNAs Expression in Cervical Cancer: Human Papillomavirus Implications

    PubMed Central

    Gómez-Gómez, Yazmín; Organista-Nava, Jorge; Gariglio, Patricio

    2013-01-01

    MicroRNAs (miRNAs) are a class of small non coding RNAs of 18–25 nucleotides in length. The temporal or short-lived expression of the miRNAs modulates gene expression post transcriptionally. Studies have revealed that miRNAs deregulation correlates and is involved with the initiation and progression of human tumors. Cervical cancer (CC) displays notably increased or decreased expression of a large number of cellular oncogenic or tumor suppressive miRNAs, respectively. However, understanding the potential role of miRNAs in CC is still limited. In CC, the high-risk human papillomaviruses (HR-HPVs) infection can affect the miRNAs expression through oncoprotein E6 and E7 that contribute to viral pathogenesis, although other viral proteins might also be involved. This deregulation in the miRNAs expression has an important role in the hallmarks of CC. Interestingly, the miRNA expression profile in CC can discriminate between normal and tumor tissue and the extraordinary stability of miRNAs makes it suitable to serve as diagnostic and prognostic biomarkers of cancer. In this review, we will summarize the role of the HR-HPVs in miRNA expression, the role of miRNAs in the hallmarks of CC, and the use of miRNAs as potential prognostic biomarkers in CC. PMID:24490161

  9. Human milk miRNAs primarily originate from the mammary gland resulting in unique miRNA profiles of fractionated milk

    PubMed Central

    Alsaweed, Mohammed; Lai, Ching Tat; Hartmann, Peter E.; Geddes, Donna T.; Kakulas, Foteini

    2016-01-01

    Human milk (HM) contains regulatory biomolecules including miRNAs, the origin and functional significance of which are still undetermined. We used TaqMan OpenArrays to profile 681 mature miRNAs in HM cells and fat, and compared them with maternal peripheral blood mononuclear cells (PBMCs) and plasma, and bovine and soy infant formulae. HM cells and PBMCs (292 and 345 miRNAs, respectively) had higher miRNA content than HM fat and plasma (242 and 219 miRNAs, respectively) (p < 0.05). A strong association in miRNA profiles was found between HM cells and fat, whilst PBMCs and plasma were distinctly different to HM, displaying marked inter-individual variation. Considering the dominance of epithelial cells in mature milk of healthy women, these results suggest that HM miRNAs primarily originate from the mammary epithelium, whilst the maternal circulation may have a smaller contribution. Our findings demonstrate that unlike infant formulae, which contained very few human miRNA, HM is a rich source of lactation-specific miRNA, which could be used as biomarkers of the performance and health status of the lactating mammary gland. Given the recently identified stability, uptake and functionality of food- and milk-derived miRNA in vivo, HM miRNA are likely to contribute to infant protection and development. PMID:26854194

  10. Hydroxytyrosol supplementation modulates the expression of miRNAs in rodents and in humans.

    PubMed

    Tomé-Carneiro, Joao; Crespo, María Carmen; Iglesias-Gutierrez, Eduardo; Martín, Roberto; Gil-Zamorano, Judit; Tomas-Zapico, Cristina; Burgos-Ramos, Emma; Correa, Carlos; Gómez-Coronado, Diego; Lasunción, Miguel A; Herrera, Emilio; Visioli, Francesco; Dávalos, Alberto

    2016-08-01

    Dietary microRNAs (miRNAs) modulation could be important for health and wellbeing. Part of the healthful activities of polyphenols might be due to a modulation of miRNAs' expression. Among the most biologically active polyphenols, hydroxytyrosol (HT) has never been studied for its actions on miRNAs. We investigated whether HT could modulate the expression of miRNAs in vivo. We performed an unbiased intestinal miRNA screening in mice supplemented (for 8 weeks) with nutritionally relevant amounts of HT. HT modulated the expression of several miRNAs. Analysis of other tissues revealed consistent HT-induced modulation of only few miRNAs. Also, HT administration increased triglycerides levels. Acute treatment with HT and in vitro experiments provided mechanistic insights. The HT-induced expression of one miRNA was confirmed in healthy volunteers supplemented with HT in a randomized, double-blind and placebo-controlled trial. HT consumption affects specific miRNAs' expression in rodents and humans. Our findings suggest that the modulation of miRNAs' action through HT consumption might partially explain its healthful activities and might be pharmanutritionally exploited in current therapies targeting endogenous miRNAs. However, the effects of HT on triglycerides warrant further investigations.

  11. miRNAs in the pathogenesis of oncogenic human viruses

    PubMed Central

    Lin, Zhen; Flemington, Erik K.

    2010-01-01

    Tumor viruses are a class of pathogens with well established roles in the development of malignant diseases. Numerous bodies of work have highlighted miRNAs (microRNAs) as critical regulators of tumor pathways and it is clear that the dysregulation of cellular miRNA expression can promote tumor formation. Tumor viruses encode their own miRNAs and/or manipulate the expression of cellular miRNAs to modulate their host cell environment, thereby facilitating their respective infection cycles. The modulation of these miRNA responsive pathways, however, often influences certain signal transduction cascades in ways that favor tumorigenesis. In this review, we discuss the roles of virally-encoded and virally-regulated cellular miRNAs in the respective viral life-cycles and in virus associated pathogenesis. PMID:20943311

  12. Uptake of dietary milk miRNAs by adult humans: a validation study

    PubMed Central

    Auerbach, Amanda; Vyas, Gopi; Li, Anne; Halushka, Marc; Witwer, Kenneth

    2016-01-01

    Breast milk is replete with nutritional content as well as nucleic acids including microRNAs (miRNAs). In a recent report, adult humans who drank bovine milk appeared to have increased circulating levels of miRNAs miR-29b-3p and miR-200c-3p. Since these miRNAs are homologous between human and cow, these results could be explained by xeno-miRNA influx, endogenous miRNA regulation, or both. More data were needed to validate the results and explore for additional milk-related alterations in circulating miRNAs. Samples from the published study were obtained, and 223 small RNA features were profiled with a custom OpenArray, followed by individual quantitative PCR assays for selected miRNAs. Additionally, small RNA sequencing (RNA-seq) data obtained from plasma samples of the same project were analyzed to find human and uniquely bovine miRNAs. OpenArray revealed no significantly altered miRNA signals after milk ingestion, and this was confirmed by qPCR. Plasma sequencing data contained no miR-29b or miR-200c reads and no intake-consistent mapping of uniquely bovine miRNAs. In conclusion, the results do not support transfer of dietary xenomiRs into the circulation of adult humans. PMID:27158459

  13. Epigenetic regulation of normal human mammary cell type-specific miRNAs

    SciTech Connect

    Vrba, Lukas; Garbe, James C.; Stampfer, Martha R.; Futscher, Bernard W.

    2011-08-26

    Epigenetic mechanisms are important regulators of cell type–specific genes, including miRNAs. In order to identify cell type-specific miRNAs regulated by epigenetic mechanisms, we undertook a global analysis of miRNA expression and epigenetic states in three isogenic pairs of human mammary epithelial cells (HMEC) and human mammary fibroblasts (HMF), which represent two differentiated cell types typically present within a given organ, each with a distinct phenotype and a distinct epigenotype. While miRNA expression and epigenetic states showed strong interindividual concordance within a given cell type, almost 10% of the expressed miRNA showed a cell type–specific pattern of expression that was linked to the epigenetic state of their promoter. The tissue-specific miRNA genes were epigenetically repressed in nonexpressing cells by DNA methylation (38%) and H3K27me3 (58%), with only a small set of miRNAs (21%) showing a dual epigenetic repression where both DNA methylation and H3K27me3 were present at their promoters, such as MIR10A and MIR10B. Individual miRNA clusters of closely related miRNA gene families can each display cell type–specific repression by the same or complementary epigenetic mechanisms, such as the MIR200 family, and MIR205, where fibroblasts repress MIR200C/141 by DNA methylation, MIR200A/200B/429 by H3K27me3, and MIR205 by both DNA methylation and H3K27me3. Since deregulation of many of the epigenetically regulated miRNAs that we identified have been linked to disease processes such as cancer, it is predicted that compromise of the epigenetic control mechanisms is important for this process. Overall, these results highlight the importance of epigenetic regulation in the control of normal cell type–specific miRNA expression.

  14. miRNA Expression in Control and FSHD Fetal Human Muscle Biopsies

    PubMed Central

    Portilho, Débora Morueco; Alves, Marcelo Ribeiro; Kratassiouk, Gueorgui; Roche, Stéphane; Magdinier, Frédérique; de Santana, Eliane Corrêa; Polesskaya, Anna; Harel-Bellan, Annick; Mouly, Vincent; Savino, Wilson; Butler-Browne, Gillian; Dumonceaux, Julie

    2015-01-01

    Background Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal-dominant disorder and is one of the most common forms of muscular dystrophy. We have recently shown that some hallmarks of FSHD are already expressed in fetal FSHD biopsies, thus opening a new field of investigation for mechanisms leading to FSHD. As microRNAs (miRNAs) play an important role in myogenesis and muscle disorders, in this study we compared miRNAs expression levels during normal and FSHD muscle development. Methods Muscle biopsies were obtained from quadriceps of both healthy control and FSHD1 fetuses with ages ranging from 14 to 33 weeks of development. miRNA expression profiles were analyzed using TaqMan Human MicroRNA Arrays. Results During human skeletal muscle development, in control muscle biopsies we observed changes for 4 miRNAs potentially involved in secondary muscle fiber formation and 5 miRNAs potentially involved in fiber maturation. When we compared the miRNA profiles obtained from control and FSHD biopsies, we did not observe any differences in the muscle specific miRNAs. However, we identified 8 miRNAs exclusively expressed in FSHD1 samples (miR-330, miR-331-5p, miR-34a, miR-380-3p, miR-516b, miR-582-5p, miR-517* and miR-625) which could represent new biomarkers for this disease. Their putative targets are mainly involved in muscle development and morphogenesis. Interestingly, these FSHD1 specific miRNAs do not target the genes previously described to be involved in FSHD. Conclusions This work provides new candidate mechanisms potentially involved in the onset of FSHD pathology. Whether these FSHD specific miRNAs cause deregulations during fetal development, or protect against the appearance of the FSHD phenotype until the second decade of life still needs to be investigated. PMID:25692472

  15. Insights into MiRNA Regulation of the Human Glycome

    PubMed Central

    Kasper, Brian T.; Koppolu, Sujeethraj; Mahal, Lara K.

    2014-01-01

    Glycosylation is an intricate process requiring the coordinated action of multiple proteins, including glycosyltransferases, glycosidases, sugar nucleotide transporters and trafficking proteins. Work by several groups points to a role for microRNA (miRNA) in controlling the levels of specific glycosyltransferases involved in cancer, neural migration and osteoblast formation. Recent work in our laboratory suggests that miRNA are a principal regulator of the glycome, translating genomic information into the glycocode through tuning of enzyme levels. Herein we overlay predicted miRNA regulation of glycosylation related genes (glycogenes) onto maps of the common N-linked and O-linked glycan biosynthetic pathways to identify key regulatory nodes of the glycome. Our analysis provides insights into glycan regulation and suggests that at the regulatory level, glycogenes are non-redundant. PMID:24463102

  16. Fractionation of human spermatogenic cells using STA-PUT gravity sedimentation and their miRNA profiling.

    PubMed

    Liu, Yun; Niu, Minghui; Yao, Chencheng; Hai, Yanan; Yuan, Qingqing; Liu, Yang; Guo, Ying; Li, Zheng; He, Zuping

    2015-01-30

    Human spermatogenic cells have not yet been isolated, and notably, their global miRNA profiles remain unknown. Here we have effectively isolated human spermatogonia, pachytene spermatocytes and round spermatids using STA-PUT velocity sedimentation. RT-PCR, immunocytochemistry and meiosis spread assays revealed that the purities of isolated human spermatogonia, pachytene spermatocytes, and round spermatids were 90%, and the viability of these isolated cells was over 98%. MiRNA microarrays showed distinct global miRNA profiles among human spermatogonia, pachytene spermatocytes, and round spermatids. Thirty-two miRNAs were significantly up-regulated whereas 78 miRNAs were down-regulated between human spermatogonia and pachytene spermatocytes, suggesting that these miRNAs are involved in the meiosis and mitosis, respectively. In total, 144 miRNAs were significantly up-regulated while 29 miRNAs were down-regulated between pachytene spermatocytes and round spermatids, reflecting potential roles of these miRNAs in mediating spermiogenesis. A number of novel binding targets of miRNAs were further identified using various softwares and verified by real-time PCR. Our ability of isolating human spermatogonia, pachytene spermatocytes and round spermatids and unveiling their distinct global miRNA signatures and novel targets could provide novel small RNA regulatory mechanisms mediating three phases of human spermatogenesis and offer new targets for the treatment of male infertility.

  17. Signatures of purifying and local positive selection in human miRNAs.

    PubMed

    Quach, Hélène; Barreiro, Luis B; Laval, Guillaume; Zidane, Nora; Patin, Etienne; Kidd, Kenneth K; Kidd, Judith R; Bouchier, Christiane; Veuille, Michel; Antoniewski, Christophe; Quintana-Murci, Lluís

    2009-03-01

    MicroRNAs (miRNAs) are noncoding RNAs involved in posttranscriptional gene repression, and their role in diverse physiological processes is increasingly recognized. Yet, few efforts have been devoted to evolutionary studies of human miRNAs. Knowledge about the way in which natural selection has targeted miRNAs should provide insight into their functional relevance as well as their mechanisms of action. Here we used miRNAs as a model system for investigating the influence of natural selection on gene regulation by characterizing the full spectrum of naturally occurring sequence variation of 117 human miRNAs from different populations worldwide. We found that purifying selection has globally constrained the diversity of miRNA-containing regions and has strongly targeted the mature miRNA. This observation emphasizes that mutations in these molecules are likely to be deleterious, and therefore they can have severe phenotypic consequences on human health. More importantly, we obtained evidence of population-specific events of positive selection acting on a number of miRNA-containing regions. Notably, our analysis revealed that positive selection has targeted a "small-RNA-rich island" on chromosome 14, harboring both miRNAs and small nucleolar RNAs, in Europeans and East Asians. These observations support the notion that the tuning of gene expression contributes to the processes by which populations adapt to specific environments. These findings will fuel future investigations exploring how genetic and functional variation of miRNAs under selection affects the repression of their mRNA targets, increasing our understanding of the role of gene regulation in population adaptation and human disease.

  18. Visual preference in a human-reared agile gibbon (Hylobates agilis).

    PubMed

    Tanaka, Masayuki; Uchikoshi, Makiko

    2010-01-01

    Visual preference was evaluated in a male agile gibbon. The subject was raised by humans immediately after birth, but lived with his biological family from one year of age. Visual preference was assessed using a free-choice task in which five or six photographs of different primate species, including humans, were presented on a touch-sensitive screen. The subject touched one of them. Food rewards were delivered irrespective of the subject's responses. We prepared two types of stimulus sets. With set 1, the subject touched photographs of humans more frequently than those of other species, recalling previous findings in human-reared chimpanzees. With set 2, photographs of nine species of gibbons were presented. Chimpanzees touched photographs of white-handed gibbons more than those of other gibbon species. The gibbon subject initially touched photographs of agile gibbons more than white-handed gibbons, but after one and two years his choice patterns resembled the chimpanzees'. The results suggest that, as in chimpanzees, visual preferences of agile gibbons are not genetically programmed but develop through social experience during infancy.

  19. Distinct AGO1 and AGO2 associated miRNA profiles in human cells and blood plasma

    PubMed Central

    Turchinovich, Andrey; Burwinkel, Barbara

    2012-01-01

    Studies of miRNA association with Argonaute (AGO) proteins in mammalian cells have indicated lack of bias toward particular AGO. However, to our knowledge, the use of quantitative methods for studying miRNA association with different AGOs has not been reported so far. In this work we compared the total miRNA content in AGO1 and AGO2 immunoprecipitates obtained from MCF7 adenocarcinoma cells using TaqMan Low Density miRNA Arrays and successfully verified selected miRNAs with qPCR. For most of the miRNA species AGO1 and AGO2 profiles were well correlated, however, some miRNAs demonstrated consistent biases toward one of the Argonautes. Furthermore, miRNAs which were predominantly AGO2-associated derived mostly from sense strands of the corresponding pre-miRNAs while the majority of AGO1 biased miRNAs originated from antisense strands of the pre-miRNAs. Additionally, we show that circulating miRNA in human blood plasma can be immunoprecipitated with both AGO1 and AGO2 antibody. However, unlike in cell lysates, AGO1 and AGO2 associated miRNA profiles in plasma did not correlate, indicating that many cell types contribute to circulating miRNA (given that expression of AGO proteins is tissue specific). Furthermore, AGO-specific miRNA profiles in blood cells differed significantly from miRNAs profiles in plasma indicating that most circulating miRNAs are likely to derive from non-blood cells. Since circulating miRNAs hold great promise as biomarkers for numerous cancers and other diseases, we hypothesize that AGO-specific miRNA profiles might add an additional dimension to circulating miRNA-based diagnostics. PMID:22858679

  20. Measurement of precursor miRNA in exosomes from human ESC-derived mesenchymal stem cells.

    PubMed

    Chen, Tian Sheng; Lim, Sai Kiang

    2013-01-01

    Mesenchymal stem cells (MSCs) derived from human embryonic stem cells (ESCs) have been shown to secrete exosomes that are cardioprotective against myocardial ischemia reperfusion injury in a mouse model. To elucidate this cardioprotective mechanism, we have characterized the protein, nucleic acid, and lipid composition of MSC exosomes. Here we describe the isolation and analysis of RNA in MSC exosome. We have previously reported that RNAs in MSC exosome are primarily small RNA molecules of <300 nt and they include many miRNAs. Many of these miRNAs are in the precursor form suggesting that pre-miRNAs, and not mature miRNAs are preferentially loaded into exosomes. The protocols described here include assays to ascertain the presence of pre-miRNAs, profiling of miRNA and pre-miRNA, and quantitative estimation of mature and pre-miRNA.

  1. Biological basis of miRNA action when their targets are located in human protein coding region.

    PubMed

    Gu, Wanjun; Wang, Xiaofei; Zhai, Chuanying; Zhou, Tong; Xie, Xueying

    2013-01-01

    Recent analyses have revealed many functional microRNA (miRNA) targets in mammalian protein coding regions. But, the mechanisms that ensure miRNA function when their target sites are located in protein coding regions of mammalian mRNA transcripts are largely unknown. In this paper, we investigate some potential biological factors, such as target site accessibility and local translation efficiency. We computationally analyze these two factors using experimentally identified miRNA targets in human protein coding region. We find site accessibility is significantly increased in miRNA target region to facilitate miRNA binding. At the mean time, local translation efficiency is also selectively decreased near miRNA target region. GC-poor codons are preferred in the flank region of miRNA target sites to ease the access of miRNA targets. Within-genome analysis shows substantial variations of site accessibility and local translation efficiency among different miRNA targets in the genome. Further analyses suggest target gene's GC content and conservation level could explain some of the differences in site accessibility. On the other hand, target gene's functional importance and conservation level can affect local translation efficiency near miRNA target region. We hence propose both site accessibility and local translation efficiency are important in miRNA action when miRNA target sites are located in mammalian protein coding regions.

  2. Intense Collaboration: Human and Technical Requirements for Agile C2

    DTIC Science & Technology

    2009-06-01

    2002). Training individuals for distributed teams: problem solving assessment for distributed mission research. Computers in Human Behavior 18...1999). Training team problem solving skills: An event-based approach. Computers in Human Behavior 15, 441-462.   22 Parasuraman, R., Sheridan

  3. Human Milk Cells Contain Numerous miRNAs that May Change with Milk Removal and Regulate Multiple Physiological Processes.

    PubMed

    Alsaweed, Mohammed; Lai, Ching Tat; Hartmann, Peter E; Geddes, Donna T; Kakulas, Foteini

    2016-06-17

    Human milk (HM) is a complex biofluid conferring nutritional, protective and developmental components for optimal infant growth. Amongst these are maternal cells, which change in response to feeding and were recently shown to be a rich source of miRNAs. We used next generation sequencing to characterize the cellular miRNA profile of HM collected before and after feeding. HM cells conserved higher miRNA content than the lipid and skim HM fractions or other body fluids, in accordance with previous studies. In total, 1467 known mature and 1996 novel miRNAs were identified, with 89 high-confidence novel miRNAs. HM cell content was higher post-feeding (p < 0.05), and was positively associated with total miRNA content (p = 0.014) and species number (p < 0.001). This coincided with upregulation of 29 known and 2 novel miRNAs, and downregulation of 4 known and 1 novel miRNAs post-feeding, but no statistically significant change in expression was found for the remaining miRNAs. These findings suggest that feeding may influence the miRNA content of HM cells. The most highly and differentially expressed miRNAs were key regulators of milk components, with potential diagnostic value in lactation performance. They are also involved in the control of body fluid balance, thirst, appetite, immune response, and development, implicating their functional significance for the infant.

  4. Human Milk Cells Contain Numerous miRNAs that May Change with Milk Removal and Regulate Multiple Physiological Processes

    PubMed Central

    Alsaweed, Mohammed; Lai, Ching Tat; Hartmann, Peter E.; Geddes, Donna T.; Kakulas, Foteini

    2016-01-01

    Human milk (HM) is a complex biofluid conferring nutritional, protective and developmental components for optimal infant growth. Amongst these are maternal cells, which change in response to feeding and were recently shown to be a rich source of miRNAs. We used next generation sequencing to characterize the cellular miRNA profile of HM collected before and after feeding. HM cells conserved higher miRNA content than the lipid and skim HM fractions or other body fluids, in accordance with previous studies. In total, 1467 known mature and 1996 novel miRNAs were identified, with 89 high-confidence novel miRNAs. HM cell content was higher post-feeding (p < 0.05), and was positively associated with total miRNA content (p = 0.014) and species number (p < 0.001). This coincided with upregulation of 29 known and 2 novel miRNAs, and downregulation of 4 known and 1 novel miRNAs post-feeding, but no statistically significant change in expression was found for the remaining miRNAs. These findings suggest that feeding may influence the miRNA content of HM cells. The most highly and differentially expressed miRNAs were key regulators of milk components, with potential diagnostic value in lactation performance. They are also involved in the control of body fluid balance, thirst, appetite, immune response, and development, implicating their functional significance for the infant. PMID:27322254

  5. Agile Mythbusting

    DTIC Science & Technology

    2015-01-01

    does not fit all Scrum : The most adopted Agile method Scaling Agile Methods: Going beyond the team level methods Challenges to Agile Adoption: What’s...Arsenal Lapham, Wrubel Jan 2015 © 2015 Carnegie Mellon University. Myth: You Must Choose Agile or Waterfall – you can’t do both What about “water- scrum ...used in multiple environments, including DoD programs.1 1Start with “Agile EVM in Scrum Projects” from AGILE 2006 to get started learning about Agile

  6. Integrative miRNA and Gene Expression Profiling Analysis of Human Quiescent Hepatic Stellate Cells.

    PubMed

    Coll, Mar; El Taghdouini, Adil; Perea, Luis; Mannaerts, Inge; Vila-Casadesús, Maria; Blaya, Delia; Rodrigo-Torres, Daniel; Affò, Silvia; Morales-Ibanez, Oriol; Graupera, Isabel; Lozano, Juan José; Najimi, Mustapha; Sokal, Etienne; Lambrecht, Joeri; Ginès, Pere; van Grunsven, Leo A; Sancho-Bru, Pau

    2015-06-22

    Unveiling the regulatory pathways maintaining hepatic stellate cells (HSC) in a quiescent (q) phenotype is essential to develop new therapeutic strategies to treat fibrogenic diseases. To uncover the miRNA-mRNA regulatory interactions in qHSCs, HSCs were FACS-sorted from healthy livers and activated HSCs (aHSCs) were generated in vitro. MiRNA Taqman array analysis showed HSCs expressed a low number of miRNAs (n = 259), from which 47 were down-regulated and 212 up-regulated upon activation. Computational integration of miRNA and gene expression profiles revealed that 66% of qHSC-associated miRNAs correlated with more than 6 altered target mRNAs (17,28 ± 10,7 targets/miRNA) whereas aHSC-associated miRNAs had an average of 1,49 targeted genes. Interestingly, interaction networks generated by miRNA-targeted genes in qHSCs were associated with key HSC activation processes. Next, selected miRNAs were validated in healthy and cirrhotic human livers and miR-192 was chosen for functional analysis. Down-regulation of miR-192 in HSCs was found to be an early event during fibrosis progression in mouse models of liver injury. Moreover, mimic assays for miR-192 in HSCs revealed its role in HSC activation, proliferation and migration. Together, these results uncover the importance of miRNAs in the maintenance of the qHSC phenotype and form the basis for understanding the regulatory networks in HSCs.

  7. Integrative miRNA and Gene Expression Profiling Analysis of Human Quiescent Hepatic Stellate Cells

    PubMed Central

    Coll, Mar; Taghdouini, Adil El; Perea, Luis; Mannaerts, Inge; Vila-Casadesús, Maria; Blaya, Delia; Rodrigo-Torres, Daniel; Affò, Silvia; Morales-Ibanez, Oriol; Graupera, Isabel; Lozano, Juan José; Najimi, Mustapha; Sokal, Etienne; Lambrecht, Joeri; Ginès, Pere; van Grunsven, Leo A.; Sancho-Bru, Pau

    2015-01-01

    Unveiling the regulatory pathways maintaining hepatic stellate cells (HSC) in a quiescent (q) phenotype is essential to develop new therapeutic strategies to treat fibrogenic diseases. To uncover the miRNA-mRNA regulatory interactions in qHSCs, HSCs were FACS-sorted from healthy livers and activated HSCs (aHSCs) were generated in vitro. MiRNA Taqman array analysis showed HSCs expressed a low number of miRNAs (n = 259), from which 47 were down-regulated and 212 up-regulated upon activation. Computational integration of miRNA and gene expression profiles revealed that 66% of qHSC-associated miRNAs correlated with more than 6 altered target mRNAs (17,28 ± 10,7 targets/miRNA) whereas aHSC-associated miRNAs had an average of 1,49 targeted genes. Interestingly, interaction networks generated by miRNA-targeted genes in qHSCs were associated with key HSC activation processes. Next, selected miRNAs were validated in healthy and cirrhotic human livers and miR-192 was chosen for functional analysis. Down-regulation of miR-192 in HSCs was found to be an early event during fibrosis progression in mouse models of liver injury. Moreover, mimic assays for miR-192 in HSCs revealed its role in HSC activation, proliferation and migration. Together, these results uncover the importance of miRNAs in the maintenance of the qHSC phenotype and form the basis for understanding the regulatory networks in HSCs. PMID:26096707

  8. Human Breast Milk miRNA, Maternal Probiotic Supplementation and Atopic Dermatitis in Offspring

    PubMed Central

    Simpson, Melanie Rae; Brede, Gaute; Johansen, Jostein; Johnsen, Roar; Storrø, Ola; Sætrom, Pål; Øien, Torbjørn

    2015-01-01

    Background Perinatal probiotic ingestion has been shown to prevent atopic dermatitis (AD) in infancy in a number of randomised trials. The Probiotics in the Prevention of Allergy among Children in Trondheim (ProPACT) trial involved a probiotic supplementation regime given solely to mothers in the perinatal period and demonstrated a ~40% relative risk reduction in the cumulative incidence of AD at 2 years of age. However, the mechanisms behind this effect are incompletely understood. Micro-RNAs (miRNA) are abundant in mammalian milk and may influence the developing gastrointestinal and immune systems of newborn infants. The objectives of this study were to describe the miRNA profile of human breast milk, and to investigate breast milk miRNAs as possible mediators of the observed preventative effect of probiotics. Methods Small RNA sequencing was conducted on samples collected 3 months postpartum from 54 women participating in the ProPACT trial. Differential expression of miRNA was assessed for the probiotic vs placebo and AD vs non-AD groups. The results were further analysed using functional prediction techniques. Results Human breast milk samples contain a relatively stable core group of highly expressed miRNAs, including miR-148a-3p, miR-22-3p, miR-30d-5p, let-7b-5p and miR-200a-3p. Functional analysis of these miRNAs revealed enrichment in a broad range of biological processes and molecular functions. Although several miRNAs were found to be differentially expressed on comparison of the probiotic vs placebo and AD vs non-AD groups, none had an acceptable false discovery rate and their biological significance in the development of AD is not immediately apparent from their predicted functional consequences. Conclusion Whilst breast milk miRNAs have the potential to be active in a diverse range of tissues and biological process, individual miRNAs in breast milk 3 months postpartum are unlikely to play a major role in the prevention of atopic dermatitis in infancy

  9. Regulation of PP2Cm expression by miRNA-204/211 and miRNA-22 in mouse and human cells

    PubMed Central

    Pan, Bang-fen; Gao, Chen; Ren, Shu-xun; Wang, Yi-bin; Sun, Hai-peng; Zhou, Mei-yi

    2015-01-01

    Aim: The mitochondrial targeted 2C-type serine/threonine protein phosphatase (PP2Cm) is encoded by the gene PPM1K and is highly conserved among vertebrates. PP2Cm plays a critical role in branched-chain amino acid catabolism and regulates cell survival. Its expression is dynamically regulated by the nutrient environment and pathological stresses. However, little is known about the molecular mechanism underlying the regulation of PPM1K gene expression. In this study, we aimed to reveal how PPM1K expression is affected by miRNA-mediated post-transcriptional regulation. Methods: Computational analysis based on conserved miRNA binding motifs was applied to predict the candidate miRNAs that potentially affect PPM1K expression. Dual-luciferase reporter assay was performed to verify the miRNAs' binding sites in the PPM1K gene and their influence on PPM1K 3′UTR activity. We further over-expressed the mimics of these miRNAs in human and mouse cells to examine whether miRNAs affected the mRNA level of PPM1K. Results: Computational analysis identified numerous miRNAs potentially targeting PPM1K. Luciferase reporter assays demonstrated that the 3′UTR of PPM1K gene contained the recognition sites of miR-204 and miR-211. Overexpression of these miRNAs in human and mouse cells diminished the 3′UTR activity and the endogenous mRNA level of PPM1K. However, the miR-22 binding site was found only in human and not mouse PPM1K 3′UTR. Accordingly, PPM1K 3′UTR activity was suppressed by miR-22 overexpression in human but not mouse cells. Conclusion: These data suggest that different miRNAs contribute to the regulation of PP2Cm expression in a species-specific manner. miR-204 and miR-211 are efficient in both mouse and human cells, while miR-22 regulates PP2Cm expression only in human cells. PMID:26592513

  10. Prediction of human miRNA target genes using computationally reconstructed ancestral mammalian sequences

    PubMed Central

    Leclercq, Mickael; Diallo, Abdoulaye Baniré; Blanchette, Mathieu

    2017-01-01

    MicroRNAs (miRNA) are short single-stranded RNA molecules derived from hairpin-forming precursors that play a crucial role as post-transcriptional regulators in eukaryotes and viruses. In the past years, many microRNA target genes (MTGs) have been identified experimentally. However, because of the high costs of experimental approaches, target genes databases remain incomplete. Although several target prediction programs have been developed in the recent years to identify MTGs in silico, their specificity and sensitivity remain low. Here, we propose a new approach called MirAncesTar, which uses ancestral genome reconstruction to boost the accuracy of existing MTGs prediction tools for human miRNAs. For each miRNA and each putative human target UTR, our algorithm makes uses of existing prediction tools to identify putative target sites in the human UTR, as well as in its mammalian orthologs and inferred ancestral sequences. It then evaluates evidence in support of selective pressure to maintain target site counts (rather than sequences), accounting for the possibility of target site turnover. It finally integrates this measure with several simpler ones using a logistic regression predictor. MirAncesTar improves the accuracy of existing MTG predictors by 26% to 157%. Source code and prediction results for human miRNAs, as well as supporting evolutionary data are available at http://cs.mcgill.ca/∼blanchem/mirancestar. PMID:27899600

  11. MiRNA-133b promotes the proliferation of human Sertoli cells through targeting GLI3

    PubMed Central

    Yao, Chencheng; Sun, Min; Yuan, Qingqing; Niu, Minghui; Chen, Zheng; Hou, Jingmei; Wang, Hong; Wen, Liping; Liu, Yun; Li, Zheng; He, Zuping

    2016-01-01

    Sertoli cells play critical roles in regulating spermatogenesis and they can be reprogrammed to the cells of other lineages, highlighting that they have significant applications in reproductive and regenerative medicine. The fate determinations of Sertoli cells are regulated precisely by epigenetic factors. However, the expression, roles, and targets of microRNA (miRNA) in human Sertoli cells remain unknown. Here we have for the first time revealed that 174 miRNAs were distinctly expressed in human Sertoli cells between Sertoli-cell-only syndrome (SCOS) patients and obstructive azoospermia (OA) patients with normal spermatogenesis using miRNA microarrays and real time PCR, suggesting that these miRNAs may be associated with the pathogenesis of SCOS. MiR-133b is upregulated in Sertoli cells of SCOS patients compared to OA patients. Proliferation assays with miRNA mimics and inhibitors showed that miR-133b enhanced the proliferation of human Sertoli cells. Moreover, we demonstrated that GLI3 was a direct target of miR-133b and the expression of Cyclin B1 and Cyclin D1 was enhanced by miR-133b mimics but decreased by its inhibitors. Gene silencing of GLI3 using RNA inference stimulated the growth of human Sertoli cells. Collectively, miR-133b promoted the proliferation of human Sertoli cells by targeting GLI3. This study thus sheds novel insights into epigenetic regulation of human Sertoli cells and the etiology of azoospermia and offers new targets for treating male infertility PMID:26755652

  12. A Panel of Serum MiRNA Biomarkers for the Diagnosis of Severe to Mild Traumatic Brain Injury in Humans

    PubMed Central

    Bhomia, Manish; Balakathiresan, Nagaraja S.; Wang, Kevin K.; Papa, Linda; Maheshwari, Radha K.

    2016-01-01

    MicroRNAs (MiRNAs) are small endogenous RNA molecules and have emerged as novel serum diagnostic biomarkers for several diseases due to their stability and detection at minute quantities. In this study, we have identified a serum miRNA signature in human serum samples of mild to severe TBI, which can be used for diagnosis of mild and moderate TBI (MMTBI). Human serum samples of MMTBI, severe TBI (STBI), orthopedic injury and healthy controls were used and miRNA profiling was done using taqman real time PCR. The real time PCR data for the MMTBI, STBI and orthopedic injury was normalized to the control samples which showed upregulation of 39, 37 and 33 miRNAs in MMTBI, STBI and orthopedic injury groups respectively. TBI groups were compared to orthopedic injury group and an up-regulation of 18 and 20 miRNAs in MMTBI and STBI groups was observed. Among these, a signature of 10 miRNAs was found to be present in both MMTBI and STBI groups. These 10 miRNAs were validated in cerebrospinal fluid (CSF) from STBI and four miRNAs were found to be upregulated in CSF. In conclusion, we identified a subset of 10 unique miRNAs which can be used for diagnosis of MMTBI and STBI. PMID:27338832

  13. MiRNA expression profiling in human gliomas: upregulated miR-363 increases cell survival and proliferation.

    PubMed

    Conti, Alfredo; Romeo, Sara G; Cama, Annamaria; La Torre, Domenico; Barresi, Valeria; Pezzino, Gaetana; Tomasello, Chiara; Cardali, Salvatore; Angileri, Filippo F; Polito, Francesca; Ferlazzo, Guido; Di Giorgio, Rosamaria; Germanò, Antonino; Aguennouz, M'hammed

    2016-10-01

    The role of microRNAs (miRNAs) in glioma biology is increasingly recognized. To investigate the regulatory mechanisms governing the malignant signature of gliomas with different grades of malignancy, we analyzed miRNA expression profiles in human grade I-IV tumor samples and primary glioma cell cultures. Multiplex real-time PCR was used to profile miRNA expression in a set of World Health Organization (WHO) grade I (pilocytic astrocytoma), II (diffuse fibrillary astrocytoma), and IV (glioblastoma multiforme) astrocytic tumors and primary glioma cell cultures. Primary glioma cell cultures were used to evaluate the effect of transfection of specific miRNAs and miRNA inhibitors. miRNA microarray showed that a set of miRNAs was consistently upregulated in all glioma samples. miR-363 was upregulated in all tumor specimens and cell lines, and its expression correlated with tumor grading. The transfection of glioma cells with the specific inhibitor of miR-363 increased the expression level of tumor suppressor growth-associated protein 43 (GAP-43). Transfection of miR-363 induced cell survival, while inhibition of miR-363 significantly reduced glioma cell viability. Furthermore, miRNA-363 inhibition induced the downregulation of AKT, cyclin-D1, matrix metalloproteinase (MMP)-2, MMP-9, and Bcl-2 and upregulation of caspase 3. Together, these data suggest that the upregulation of miR-363 may play a role in malignant glioma signature.

  14. dbDEMC 2.0: updated database of differentially expressed miRNAs in human cancers

    PubMed Central

    Yang, Zhen; Wu, Liangcai; Wang, Anqiang; Tang, Wei; Zhao, Yi; Zhao, Haitao; Teschendorff, Andrew E.

    2017-01-01

    MicroRNAs (miRNAs) are often deregulated in cancer and are thought to play an important role in cancer development. Large amount of differentially expressed miRNAs have been identified in various cancers by using high-throughput methods. It is therefore quite important to make a comprehensive collection of these miRNAs and to decipher their roles in oncogenesis and tumor progression. In 2010, we presented the first release of dbDEMC, representing a database for collection of differentially expressed miRNAs in human cancers obtained from microarray data. Here we describe an update of the database. dbDEMC 2.0 documents 209 expression profiling data sets across 36 cancer types and 73 subtypes, and a total of 2224 differentially expressed miRNAs were identified. An easy-to-use web interface was constructed that allows users to make a quick search of the differentially expressed miRNAs in certain cancer types. In addition, a new function of ‘meta-profiling’ was added to view differential expression events according to user-defined miRNAs and cancer types. We expect this database to continue to serve as a valuable source for cancer investigation and potential clinical application related to miRNAs. dbDEMC 2.0 is freely available at http://www.picb.ac.cn/dbDEMC. PMID:27899556

  15. Transient Gene and miRNA Expression Profile Changes of Confluent Human Fibroblast Cells in Space

    NASA Technical Reports Server (NTRS)

    Zhang, Ye; Lu, Tao; Wong, Michael; Feiveson, Alan; Stodieck, Louis; Karouia, Fathi; Wang, Xiaoyu; Wu, Honglu

    2015-01-01

    Microgravity or an altered gravity environment from the static 1 gravitational constant has been shown to influence global gene expression patterns and protein levels in cultured cells. However, most of the reported studies conducted in space or using simulated microgravity on the ground have focused on the growth or differentiation of the cells. Whether non-dividing cultured cells will sense the presence of microgravity in space has not been specifically addressed. In an experiment conducted on the International Space Station, confluent human fibroblast cells were fixed after being cultured in space for 3 and 14 days for investigations of gene and miRNA (microRNA) expression profile changes in these cells. A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for tissues, and plays a critical role in wound healing and other functions. Results of the experiment showed that on Day 3, both the flown and ground cells were still proliferating slowly even though they were confluent, as measured by the expression of the protein Ki-67 positive cells, and the cells in space grew slightly faster. Gene and miRNA expression data indicated activation of NF(sub kappa)B (nuclear factor kappa-light-chain-enhancer of activated B cells) and other growth related pathways involving HGF and VEGF in the flown cells. On Day 14 when the cells were mostly non-dividing, the gene and miRNA expression profiles between the flight and ground samples were indistinguishable. Comparison of gene and miRNA expressions in the Day 3 samples in respect to Day 14 revealed that most of the changes observed on Day 3 were related to cell growth for both the flown and ground cells. Analysis of cytoskeleton changes by immunohistochemistry staining of the cells with antibodies for alpha-tubulin showed no difference between the flight and ground samples. Results of our study suggest that in true non-dividing human fibroblast cells, microgravity in

  16. MiRNA profile associated with replicative senescence, extended cell culture, and ectopic telomerase expression in human foreskin fibroblasts.

    PubMed

    Bonifacio, Laura N; Jarstfer, Michael B

    2010-09-01

    Senescence is a highly regulated process that limits cellular replication by enforcing a G1 arrest in response to various stimuli. Replicative senescence occurs in response to telomeric DNA erosion, and telomerase expression can offset replicative senescence leading to immortalization of many human cells. Limited data exists regarding changes of microRNA (miRNA) expression during senescence in human cells and no reports correlate telomerase expression with regulation of senescence-related miRNAs. We used miRNA microarrays to provide a detailed account of miRNA profiles for early passage and senescent human foreskin (BJ) fibroblasts as well as early and late passage immortalized fibroblasts (BJ-hTERT) that stably express the human telomerase reverse transcriptase subunit hTERT. Selected miRNAs that were differentially expressed in senescence were assayed for expression in quiescent cells to identify miRNAs that are specifically associated with senescence-associated growth arrest. From this group of senescence-associated miRNAs, we confirmed the ability of miR-143 to induce growth arrest after ectopic expression in young fibroblasts. Remarkably, miR-143 failed to induce growth arrest in BJ-hTERT cells. Importantly, the comparison of late passage immortalized fibroblasts to senescent wild type fibroblasts reveals that miR-146a, a miRNA with a validated role in regulating the senescence associated secretory pathway, is also regulated during extended cell culture independently of senescence. The discovery that miRNA expression is impacted by expression of ectopic hTERT as well as extended passaging in immortalized fibroblasts contributes to a comprehensive understanding of the connections between telomerase expression, senescence and processes of cellular aging.

  17. Empirical Agility

    DTIC Science & Technology

    2014-06-01

    documented the fact that Unmanned Aerial Vehicles (now more commonly called drones ) added substantially to the quality of surveillance, resulting in better...Battalions. CACI Inc.-Federal, Arlington, Virginia. 1977. DTIC Accession Number ADA123481. Olmstead, Joseph A., B. Leon Elder, and John M...greater agility – Drones improved agility in ground and air operations – Nelson’s C2 at Trafalgar demonstrated agility. Theater Level C2 During WW II

  18. Discovery of shear- and side-specific mRNAs and miRNAs in human aortic valvular endothelial cells

    PubMed Central

    Holliday, Casey J.; Ankeny, Randall F.; Nerem, Robert M.

    2011-01-01

    The role of endothelial cells (ECs) in aortic valve (AV) disease remains relatively unknown; however, disease preferentially occurs in the fibrosa. We hypothesized oscillatory shear (OS) present on the fibrosa stimulates ECs to modify mRNAs and microRNAs (miRNAs) inducing disease. Our goal was to identify mRNAs and miRNAs differentially regulated by OS and laminar shear (LS) in human AVECs (HAVECs) from the fibrosa (fHAVECs) and ventricularis (vHAVECs). HAVECs expressed EC markers as well as some smooth muscle cell markers and functionally aligned with the flow. HAVECs were exposed to OS and LS for 24 h, and total RNA was analyzed by mRNA and miRNA microarrays. We found over 700 and 300 mRNAs down- and upregulated, respectively, by OS; however, there was no side dependency. mRNA microarray results were validated for 26 of 28 tested genes. Ingenuity Pathway Analysis revealed thrombospondin 1 (Thbs1) and NF-κB inhibitor-α (Nfkbia) as highly connected, shear-sensitive genes. miRNA array analysis yielded 30 shear-sensitive miRNAs and 3 side-specific miRNAs. miRNA validation confirmed 4 of 17 shear-sensitive miRNAs and 1 of 3 side-dependent miRNAs. Using miRWalk and several filtering steps, we identified shear-sensitive mRNAs potentially targeted by shear-sensitive miRNAs. These genes and signaling pathways could act as therapeutic targets of AV disease. PMID:21705672

  19. 1α,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells

    PubMed Central

    Ma, Yingyu; Hu, Qiang; Luo, Wei; Pratt, Rachel N.; Glenn, Sean T.; Liu, Song; Trump, Donald L.; Johnson, Candace S.

    2014-01-01

    Bladder cancer is the fourth most commonly diagnosed cancer in men and eighth leading cause of cancer-related death in the US. Epidemiological and experimental studies strongly suggest a role for 1α,25(OH)2D3 in cancer prevention and treatment. The antitumor activities of 1α,25(OH)2D3 are mediated by the induction of cell cycle arrest, apoptosis, differentiation and the inhibition of angiogenesis and metastasis. MiRNAs play important regulatory roles in cancer development and progression. However, the role of 1α,25(OH)2D3 in the regulation of miRNA expression and the potential impact in bladder cancer has not been investigated. Therefore, we studied 1α,25(OH)2D3-regulated miRNA expression profiles in human bladder cancer cell line 253J and the highly tumorigenic and metastatic derivative line 253J-BV by miRNA qPCR panels. 253 J and 253J-BV cells express endogenous vitamin D receptor (VDR) which can be further induced by 1α,25(OH)2D3. VDR target gene 24-hydroxylase was induced by 1α,25(OH)2D3 in both cell lines, indicating functional 1α,25(OH)2D3 signaling. The miRNA qPCR panel assay results showed that 253J and 253J-BV cells have distinct miRNA expression profiles. Further, 1α,25(OH)2D3 differentially regulated miRNA expression profiles in 253J and 253 J-BV cells in a dynamic manner. Pathway analysis of the miRNA target genes revealed distinct patterns of contribution to the molecular functions and biological processes in the two cell lines. In conclusion, 1α,25(OH)2D3 differentially regulates the expression of miRNAs, which may contribute to distinct biological functions, in human bladder 253J and 253J-BV cells. PMID:25263658

  20. NCAM1 is the Target of miRNA-572: Validation in the Human Oligodendroglial Cell Line.

    PubMed

    Mancuso, Roberta; Agostini, Simone; Marventano, Ivana; Hernis, Ambra; Saresella, Marina; Clerici, Mario

    2017-03-22

    The neural cell adhesion molecule 1 (NCAM1) is a fundamental protein in cell-cell interaction and in cellular developmental processes, and its dysregulation is involved in a number of diseases including multiple sclerosis. Studies in rats suggest that the modulation of NCAM1 expression is regulated by miRNA-572, but no data are available confirming such interaction in the human system. We analyzed whether this is the case using a human oligodendroglial cell line (MO3.13). MO3.13 cells were transfected with miRNA-572 mimic and inhibitor separately; NCAM1 mRNA and protein expression levels were analyzed at different time points after transfection. Results indicated that NCAM1 expression is increased after transfection with miRNA-572 inhibitor, whereas it is decreased after transfection with the mimic (p < 0.005). The interaction between NCAM1 and miRNA-572 was subsequently confirmed in a Vero cell line that does not express NCAM1, by luciferase assay after transfection with NCAM1. These results confirm that miRNA-572 regulates NCAM1 and for the first time demonstrate that this interaction regulates NCAM1 expression in human cells. Data herein also support the hypothesis that miRNA-572 is involved in diseases associated with NCAM1 deregulation, suggesting its possible use as a biomarker in these diseases.

  1. Analyzing the miRNA-Gene Networks to Mine the Important miRNAs under Skin of Human and Mouse

    PubMed Central

    Gong, Husile

    2016-01-01

    Genetic networks provide new mechanistic insights into the diversity of species morphology. In this study, we have integrated the MGI, GEO, and miRNA database to analyze the genetic regulatory networks under morphology difference of integument of humans and mice. We found that the gene expression network in the skin is highly divergent between human and mouse. The GO term of secretion was highly enriched, and this category was specific in human compared to mouse. These secretion genes might be involved in eccrine system evolution in human. In addition, total 62,637 miRNA binding target sites were predicted in human integument genes (IGs), while 26,280 miRNA binding target sites were predicted in mouse IGs. The interactions between miRNAs and IGs in human are more complex than those in mouse. Furthermore, hsa-miR-548, mmu-miR-466, and mmu-miR-467 have an enormous number of targets on IGs, which both have the role of inhibition of host immunity response. The pattern of distribution on the chromosome of these three miRNAs families is very different. The interaction of miRNA/IGs has added the new dimension in traditional gene regulation networks of skin. Our results are generating new insights into the gene networks basis of skin difference between human and mouse. PMID:27689084

  2. A serum miRNA profile of human longevity: findings from the Baltimore Longitudinal Study of Aging (BLSA)

    PubMed Central

    Parsons, Christine; Gorospe, Myriam; Ferrucci, Luigi; Gill, Thomas M.; Slack, Frank J.

    2016-01-01

    In C. elegans, miRNAs are genetic biomarkers of aging. Similarly, multiple miRNAs are differentially expressed between younger and older persons, suggesting that miRNA-regulated biological mechanisms affecting aging are evolutionarily conserved. Previous human studies have not considered participants' lifespans, a key factor in identifying biomarkers of aging. Using PCR arrays, we measured miRNA levels from serum samples obtained longitudinally at ages 50, 55, and 60 from 16 non-Hispanic males who had documented lifespans from 58 to 92. Numerous miRNAs showed significant changes in expression levels. At age 50, 24 miRNAs were significantly upregulated, and 73 were significantly downregulated in the long-lived subgroup (76-92 years) as compared with the short-lived subgroup (58-75 years). In long-lived participants, the most upregulated was miR-373-5p, while the most downregulated was miR-15b-5p. Longitudinally, significant Pearson correlations were observed between lifespan and expression of nine miRNAs (p value<0.05). Six of these nine miRNAs (miR-211-5p, 374a-5p, 340-3p, 376c-3p, 5095, 1225-3p) were also significantly up- or downregulated when comparing long-lived and short-lived participants. Twenty-four validated targets of these miRNAs encoded aging-associated proteins, including PARP1, IGF1R, and IGF2R. We propose that the expression profiles of the six miRNAs (miR-211-5p, 374a-5p, 340-3p, 376c-3p, 5095, and 1225-3p) may be useful biomarkers of aging. PMID:27824314

  3. Energizing miRNA research: a review of the role of miRNAs in lipid metabolism, with a prediction that miR-103/107 regulates human metabolic pathways.

    PubMed

    Wilfred, Bernard R; Wang, Wang-Xia; Nelson, Peter T

    2007-07-01

    MicroRNAs (miRNAs) are powerful regulators of gene expression. Although first discovered in worm larvae, miRNAs play fundamental biological roles-including in humans-well beyond development. MiRNAs participate in the regulation of metabolism (including lipid metabolism) for all animal species studied. A review of the fascinating and fast-growing literature on miRNA regulation of metabolism can be parsed into three main categories: (1) adipocyte biochemistry and cell fate determination; (2) regulation of metabolic biochemistry in invertebrates; and (3) regulation of metabolic biochemistry in mammals. Most research into the 'function' of a given miRNA in metabolic pathways has concentrated on a given miRNA acting upon a particular 'target' mRNA. Whereas in some biological contexts the effects of a given miRNA:mRNA pair may predominate, this might not be the case generally. In order to provide an example of how a single miRNA could regulate multiple 'target' mRNAs or even entire human metabolic pathways, we include a discussion of metabolic pathways that are predicted to be regulated by the miRNA paralogs, miR-103 and miR-107. These miRNAs, which exist in vertebrate genomes within introns of the pantothenate kinase (PANK) genes, are predicted by bioinformatics to affect multiple mRNA targets in pathways that involve cellular Acetyl-CoA and lipid levels. Significantly, PANK enzymes also affect these pathways, so the miRNA and 'host' gene may act synergistically. These predictions require experimental verification. In conclusion, a review of the literature on miRNA regulation of metabolism leads us believe that the future will provide researchers with many additional energizing revelations.

  4. Bivalent histone modifications in stem cells poise miRNA loci for CpG island hypermethylation in human cancer.

    PubMed

    Iliou, Maria S; Lujambio, Amaia; Portela, Anna; Brüstle, Oliver; Koch, Philipp; Andersson-Vincent, Per Henrik; Sundström, Erik; Hovatta, Outi; Esteller, Manel

    2011-11-01

    It has been proposed that the existence of stem cell epigenetic patterns confer a greater likelihood of CpG island hypermethylation on tumor suppressor-coding genes in cancer. The suggested mechanism is based on the Polycomb-mediated methylation of K27 of histone H3 and the recruitment of DNA methyltransferases on the promoters of tumor suppressor genes in cancer cells, when those genes are preferentially pre-marked in embryonic stem cells (ESCs) with bivalent chromatin domains. On the other hand, miRNAs appear to be dysregulated in cancer, with many studies reporting silencing of miRNA genes due to aberrant hypermethylation of their promoter regions. We wondered whether a pre-existing histone modification profile in stem cells might also contribute to the DNA methylation-associated silencing of miRNA genes in cancer. To address this, we examined a group of tumor suppressor miRNA genes previously reported to become hypermethylated and inactivated specifically in cancer cells. We analyzed the epigenetic events that take place along their promoters in human embryonic stem cells and in transformed cells. Our results suggest that there is a positive correlation between the existence of bivalent chromatin domains on miRNA promoters in ESCs and the hypermethylation of those genes in cancer, leading us to conclude that this epigenetic mark could be a mechanism that prepares miRNA promoters for further DNA hypermethylation in human tumors.

  5. miRNA regulation of Sirtuin-1 expression in human astrocytoma

    PubMed Central

    Romeo, Sara Giovanna; Conti, Alfredo; Polito, Francesca; Tomasello, Chiara; Barresi, Valeria; La Torre, Domenico La; Cucinotta, Maria; Angileri, Flavio Filippo; Bartolotta, Marcello; Di Giorgio, Rosa Maria; Aguennouz, M'Hammed

    2016-01-01

    Sirtuins are a family of 7 histone deacetylases largely involved in the regulation of cell proliferation, survival and death. The role of sirtuins in tumorigenesis and cancer progression has been previously studied in certain cancer types. Few studies have investigated sirtuin expression in gliomas, with controversial results. The aim of the present study was to investigate the expression of sirtuin-1 (Sirt-1) in diffuse astrocytoma [low grade astrocytoma (LGA)], anaplastic astrocytoma (AA) and glioblastoma multiforme (GBM) and in primary glioma cell lines: PLGAC (primary LGA cells); PAAC (primary AA cells); and PGBMC (primary GBM cells). Tumor samples were obtained from patients who underwent craniotomy for microsurgical tumor resection at the Neurosurgery Unit of the University of Messina between 2011 and 2014. Sirt-1 expression was qualitatively analyzed in 30 human glial tumor samples and 5 non-neoplastic brain tissue (NBT) specimens using immunohistochemistry and western blotting techniques. Sirt-1 expression was quantitatively analyzed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, Sirt-1 expression in primary cell lines was investigated by immunoblotting and RT-qPCR. Sirt-1 expression was downregulated in gliomas compared to NBTs. Sirt-1 levels also varied among different tumor grades, with more evident downregulation in high-grade (P<0.001) than low-grade tumors (P<0.01). These data were confirmed in cell lines, with the exception of upregulation of protein level in the highest malignancy grade cell lines. The present results suggest a role for miRNA-34a, miRNA-132 and miRNA-217 in the epigenetic control of Sirt-1 during gliomagenesis and progression, and demonstrate the different implications of Sirt-1 in human tissues and cell lines. Furthermore, the present results reveal that Sirt-1 may be an intrinsic regulator of tumor progression and the regulation of Sirt-1 involves complex molecular pathways. However, the

  6. MicroRNA (miRNA) Signaling in the Human CNS in Sporadic Alzheimer's Disease (AD)-Novel and Unique Pathological Features.

    PubMed

    Zhao, Yuhai; Pogue, Aileen I; Lukiw, Walter J

    2015-12-17

    Of the approximately ~2.65 × 10³ mature microRNAs (miRNAs) so far identified in Homo sapiens, only a surprisingly small but select subset-about 35-40-are highly abundant in the human central nervous system (CNS). This fact alone underscores the extremely high selection pressure for the human CNS to utilize only specific ribonucleotide sequences contained within these single-stranded non-coding RNAs (ncRNAs) for productive miRNA-mRNA interactions and the down-regulation of gene expression. In this article we will: (i) consolidate some of our still evolving ideas concerning the role of miRNAs in the CNS in normal aging and in health, and in sporadic Alzheimer's disease (AD) and related forms of chronic neurodegeneration; and (ii) highlight certain aspects of the most current work in this research field, with particular emphasis on the findings from our lab of a small pathogenic family of six inducible, pro-inflammatory, NF-κB-regulated miRNAs including miRNA-7, miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. This group of six CNS-abundant miRNAs significantly up-regulated in sporadic AD are emerging as what appear to be key mechanistic contributors to the sporadic AD process and can explain much of the neuropathology of this common, age-related inflammatory neurodegeneration of the human CNS.

  7. 1α,25(OH)2D3 differentially regulates miRNA expression in human bladder cancer cells.

    PubMed

    Ma, Yingyu; Hu, Qiang; Luo, Wei; Pratt, Rachel N; Glenn, Sean T; Liu, Song; Trump, Donald L; Johnson, Candace S

    2015-04-01

    Bladder cancer is the fourth most commonly diagnosed cancer in men and eighth leading cause of cancer-related death in the US. Epidemiological and experimental studies strongly suggest a role for 1α,25(OH)2D3 in cancer prevention and treatment. The antitumor activities of 1α,25(OH)2D3 are mediated by the induction of cell cycle arrest, apoptosis, differentiation and the inhibition of angiogenesis and metastasis. miRNAs play important regulatory roles in cancer development and progression. However, the role of 1α,25(OH)2D3 in the regulation of miRNA expression and the potential impact in bladder cancer has not been investigated. Therefore, we studied 1α,25(OH)2D3-regulated miRNA expression profiles in human bladder cancer cell line 253J and the highly tumorigenic and metastatic derivative line 253J-BV by miRNA qPCR panels. 253J and 253J-BV cells express endogenous vitamin D receptor (VDR), which can be further induced by 1α,25(OH)2D3. VDR target gene 24-hydroxylase was induced by 1α,25(OH)2D3 in both cell lines, indicating functional 1α,25(OH)2D3 signaling. The miRNA qPCR panel assay results showed that 253J and 253J-BV cells have distinct miRNA expression profiles. Further, 1α,25(OH)2D3 differentially regulated miRNA expression profiles in 253J and 253J-BV cells in a dynamic manner. Pathway analysis of the miRNA target genes revealed distinct patterns of contribution to the molecular functions and biological processes in the two cell lines. In conclusion, 1α,25(OH)2D3 differentially regulates the expression of miRNAs, which may contribute to distinct biological functions, in human bladder 253J and 253J-BV cells. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.

  8. Detection of human microRNAs across miRNA Array and Next Generation DNA Sequencing Platforms

    EPA Science Inventory

    microRNA (miRNAs) are non-coding RNA molecules between 19 and 30 nucleotides in length that are believed to regulate approximately 30 per cent of all human genes. They act as negative regulators of their gene targets in many biological processes. Recent developments in microar...

  9. Human and Epstein-Barr Virus miRNA Profiling as Predictive Biomarkers for Endemic Burkitt Lymphoma

    PubMed Central

    Oduor, Cliff I.; Movassagh, Mercedeh; Kaymaz, Yasin; Chelimo, Kiprotich; Otieno, Juliana; Ong'echa, John M.; Moormann, Ann M.; Bailey, Jeffrey A.

    2017-01-01

    Endemic Burkitt lymphoma (eBL) is an aggressive B cell lymphoma and is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria co-infections. Central to BL oncogenesis is the over-expression of the MYC proto-oncogene which is caused by a translocation of an Ig enhancer in approximation to the myc gene. While whole genome/transcriptome sequencing methods have been used to define driver mutations and transcriptional dysregulation, microRNA (miRNA) dysregulation and differential expression has yet to be fully characterized. We hypothesized that both human and EBV miRNAs contribute to eBL clinical presentation, disease progression, and poor outcomes. Using sensitive and precise deep sequencing, we identified miRNAs from 17 Kenyan eBL patient tumor samples and delineated the complement of both host and EBV miRNAs. One human miRNA, hsa-miR-10a-5p was found to be differentially expressed (DE), being down-regulated in jaw tumors relative to abdominal and in non-survivors compared to survivors. We also examined EBV miRNAs, which made up 2.7% of the miRNA composition in the eBL samples. However, we did not find any significant associations regarding initial patient outcome or anatomical presentation. Gene ontology analysis and pathway enrichment of previously validated targets of miR-10a-5p suggest that it can promote tumor cell survival as well as aid in evasion of apoptosis. To examine miR-10a-5p regulatory effect on gene expression in eBL, we performed a pairwise correlation coefficient analysis on the expression levels of all its validated targets. We found a significant enrichment of correlated target genes consistent with miR-10a-5p impacting expression. The functions of genes and their correlation fit with multiple target genes impacting tumor resilience. The observed downregulation of miR-10a and associated genes suggests a role for miRNA in eBL patient outcomes and has potential as a predictive biomarker that warrants further investigation.

  10. Site-specific associations between miRNA expression and survival in colorectal cancer cases

    PubMed Central

    Slattery, Martha L.; Herrick, Jennifer S.; Pellatt, Daniel F.; Mullany, Lila E.; Stevens, John R.; Wolff, Erica; Hoffman, Michael D.; Wolff, Roger K.; Samowitz, Wade

    2016-01-01

    Background MicroRNAs (miRNA) are small non-coding RNA involved in cellular processes, including cell proliferation and angiogenesis. Thus, miRNA expression may alter survival after diagnosis with colorectal cancer (CRC). Results Individuals diagnosed with stage 1 or stage 2 rectal cancer had worse survival than colon cancer cases diagnosed at stage 1 or stage 2. After adjustment for multiple comparisons, no miRNAs were significantly associated with disease stage. Two miRNAs infrequently expressed in the population and not previously reported were associated with survival after diagnosis with colon cancer (miR-1 HR 2.17 95% CI 1.41, 3.36; and miR-101-3p HR 3.51 95% CI 1.72, 7.15). Among those diagnosed with rectal cancer, 201 miRNAs were associated with survival when the FDR q value was < 0.05. Assessment of 105 previously reported miRNAs associated with prognosis showed that four miRNAs influenced colon cancer survival and 17 influenced survival after a diagnosis with rectal cancer when raw p values were considered. Patients and Methods This study includes data from population-based studies of CRC conducted in Utah and the Kaiser Permanente Medical Care Program. A total of 1893 carcinoma and normal paired colorectal mucosa tissue samples were run using the Agilent Human miRNA Microarray V19.0. We assessed miRNA differential expression between paired carcinoma and normal colonic mucosa tissue with CRC- specific survival evaluating stage and site-specific associations after adjusting for age, sex, microsatellite instability tumor status, and AJCC stage. Conclusions MiRNAs dysregulated for both colon and rectal cancer had a greater impact on survival after a diagnosis with rectal cancer. PMID:27517623

  11. An integrated analysis of differential miRNA and mRNA expressions in human gallstones.

    PubMed

    Yang, Bin; Liu, Bin; Bi, Pinduan; Wu, Tao; Wang, Qiang; Zhang, Jie

    2015-04-01

    Gallstone disease, including cholesterol precipitation in bile, increased bile salt hydrophobicity and gallbladder inflammation. Here, we investigated miRNA and mRNA involved in the formation of gallstones, and explored the molecular mechanisms in the development of gallstones. Differentially expressed 17 miRNAs and 525 mRNA were identified based on Illumina sequencing from gallbladder mucosa of patients with or without gallstones, and were validated by randomly selected 6 miRNAs and 8 genes using quantitative RT-PCR. 114 miRNA target genes were identified, whose functions and regulating pathways were related to gallstones. The differentially expressed genes were enriched upon lipoprotein binding and some metabolic pathways, and differentially expressed miRNAs enriched upon ABC transportation and cancer related pathways. A molecular regulatory network consisting of 17 differentially expressed miRNAs, inclusive of their target genes, was constructed. miR-210 and its potential target gene ATP11A were found to be differentially expressed in both miRNA and mRNA profiles. ATP11A was a direct target of miR-210, which was predicted to regulate the ABC-transporters pathway. The expression levels of ATP11A in the gallstone showed inverse correlation with miR-210 expression, and up-regulation of miR-210 could reduce ATP11A expression in HGBEC. This is the first report that indicates the existence of differences in miRNA and mRNA expression in patients with or without gallstones. Our data shed light on further investigating the mechanisms of gallstone formation.

  12. MicroRNA (miRNA) Signaling in the Human CNS in Sporadic Alzheimer’s Disease (AD)-Novel and Unique Pathological Features

    PubMed Central

    Zhao, Yuhai; Pogue, Aileen I.; Lukiw, Walter J.

    2015-01-01

    Of the approximately ~2.65 × 103 mature microRNAs (miRNAs) so far identified in Homo sapiens, only a surprisingly small but select subset—about 35–40—are highly abundant in the human central nervous system (CNS). This fact alone underscores the extremely high selection pressure for the human CNS to utilize only specific ribonucleotide sequences contained within these single-stranded non-coding RNAs (ncRNAs) for productive miRNA–mRNA interactions and the down-regulation of gene expression. In this article we will: (i) consolidate some of our still evolving ideas concerning the role of miRNAs in the CNS in normal aging and in health, and in sporadic Alzheimer’s disease (AD) and related forms of chronic neurodegeneration; and (ii) highlight certain aspects of the most current work in this research field, with particular emphasis on the findings from our lab of a small pathogenic family of six inducible, pro-inflammatory, NF-κB-regulated miRNAs including miRNA-7, miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a and miRNA-155. This group of six CNS-abundant miRNAs significantly up-regulated in sporadic AD are emerging as what appear to be key mechanistic contributors to the sporadic AD process and can explain much of the neuropathology of this common, age-related inflammatory neurodegeneration of the human CNS. PMID:26694372

  13. MicroRNA profiles in colorectal carcinomas, adenomas and normal colonic mucosa: variations in miRNA expression and disease progression.

    PubMed

    Slattery, Martha L; Herrick, Jennifer S; Pellatt, Daniel F; Stevens, John R; Mullany, Lila E; Wolff, Erica; Hoffman, Michael D; Samowitz, Wade S; Wolff, Roger K

    2016-03-01

    MiRNAs are small, non-protein-coding RNA molecules that regulate gene expression either by post-transcriptionally suppressing mRNA translation or by mRNA degradation. We examine differentially expressed miRNAs in colorectal carcinomas, adenomas and normal colonic mucosa. Data come from population-based studies of colorectal cancer conducted in Utah and the Kaiser Permanente Medical Care Program. A total of 1893 carcinoma/normal-paired samples and 290 adenoma tissue samples were run on the Agilent Human miRNA Microarray V19.0 which contained 2006 miRNAs. We tested for significant differences in miRNA expression between paired carcinoma/adenoma/normal colonic tissue samples. Fewer than 600 miRNAs were expressed in >80% of people for colonic tissue; of these 86.5% were statistically differentially expressed between carcinoma and normal colonic mucosa using a false discovery rate of 0.05. Roughly half of these differentially expressed miRNAs showed a progression in levels of expression from normal to adenoma to carcinoma tissue. Other miRNAs appeared to be altered at the normal to adenoma stage, while others were only altered at the adenoma to carcinoma stage or only at the normal to carcinoma stage. Evaluation of the Agilent platform showed a high degree of repeatability (r = 0.98) and reasonable agreement with the NanoString platform. Our data suggest that miRNAs are highly dysregulated in colorectal tissue among individuals with colorectal cancer; the pattern of disruption varies by miRNA as tissue progresses from normal to adenoma to carcinoma.

  14. Human Milk Cells and Lipids Conserve Numerous Known and Novel miRNAs, Some of Which Are Differentially Expressed during Lactation.

    PubMed

    Alsaweed, Mohammed; Lai, Ching Tat; Hartmann, Peter E; Geddes, Donna T; Kakulas, Foteini

    2016-01-01

    Human milk (HM) is rich in miRNAs, which are thought to contribute to infant protection and development. We used deep sequencing to profile miRNAs in the cell and lipid fractions of HM obtained post-feeding from 10 lactating women in months 2, 4, and 6 postpartum. In both HM fractions, 1,195 mature known miRNAs were identified, which were positively associated with the cell (p = 0.048) and lipid (p = 0.010) content of HM. An additional 5,167 novel miRNA species were predicted, of which 235 were high-confidence miRNAs. HM cells contained more known miRNAs than HM lipids (1,136 and 835 respectively, p<0.001). Although the profile of the novel miRNAs was very different between cells and lipids, with the majority conserved in the cell fraction and being mother-specific, 2/3 of the known miRNAs common between cells and lipids were similarly expressed (p>0.05). Great similarities between the two HM fractions were also found in the profile of the top 20 known miRNAs. These were largely similar also between the three lactation stages examined, as were the total miRNA concentration, and the number and expression of the known miRNAs common between cells and lipids (p>0.05). Yet, approximately a third of all known miRNAs were differentially expressed during the first 6 months of lactation (p<0.05), with more pronounced miRNA upregulation seen in month 4. These findings indicate that although the total miRNA concentration of HM cells and lipids provided to the infant does not change in first 6 months of lactation, the miRNA composition is altered, particularly in month 4 compared to months 2 and 6. This may reflect the remodeling of the gland in response to infant feeding patterns, which usually change after exclusive breastfeeding, suggesting adaptation to the infant's needs.

  15. Human Milk Cells and Lipids Conserve Numerous Known and Novel miRNAs, Some of Which Are Differentially Expressed during Lactation

    PubMed Central

    Alsaweed, Mohammed; Lai, Ching Tat; Hartmann, Peter E.; Geddes, Donna T.; Kakulas, Foteini

    2016-01-01

    Human milk (HM) is rich in miRNAs, which are thought to contribute to infant protection and development. We used deep sequencing to profile miRNAs in the cell and lipid fractions of HM obtained post-feeding from 10 lactating women in months 2, 4, and 6 postpartum. In both HM fractions, 1,195 mature known miRNAs were identified, which were positively associated with the cell (p = 0.048) and lipid (p = 0.010) content of HM. An additional 5,167 novel miRNA species were predicted, of which 235 were high-confidence miRNAs. HM cells contained more known miRNAs than HM lipids (1,136 and 835 respectively, p<0.001). Although the profile of the novel miRNAs was very different between cells and lipids, with the majority conserved in the cell fraction and being mother-specific, 2/3 of the known miRNAs common between cells and lipids were similarly expressed (p>0.05). Great similarities between the two HM fractions were also found in the profile of the top 20 known miRNAs. These were largely similar also between the three lactation stages examined, as were the total miRNA concentration, and the number and expression of the known miRNAs common between cells and lipids (p>0.05). Yet, approximately a third of all known miRNAs were differentially expressed during the first 6 months of lactation (p<0.05), with more pronounced miRNA upregulation seen in month 4. These findings indicate that although the total miRNA concentration of HM cells and lipids provided to the infant does not change in first 6 months of lactation, the miRNA composition is altered, particularly in month 4 compared to months 2 and 6. This may reflect the remodeling of the gland in response to infant feeding patterns, which usually change after exclusive breastfeeding, suggesting adaptation to the infant’s needs. PMID:27074017

  16. Integrated analysis of miRNA and mRNA during differentiation of human CD34+ cells delineates the regulatory roles of microRNA in hematopoiesis.

    PubMed

    Raghavachari, Nalini; Liu, Poching; Barb, Jennifer J; Yang, Yanqin; Wang, Richard; Nguyen, Quang Tri; Munson, Peter J

    2014-01-01

    In the process of human hematopoiesis, precise regulation of the expression of lineage-specific gene products is critical for multiple cell-fate decisions that govern cell differentiation, proliferation, and self-renewal. Given the important role of microRNAs (miRNAs) in development and differentiation, we examined the global expression of miRNA in CD34(+) cells during lineage specific hematopoiesis and found 49 miRNAs to be differentially expressed, with functional roles in cellular growth and proliferation, and apoptosis. miR-18a was upregulated during erythropoiesis and downregulated during megakaryopoiesis. miR-145 was upregulated during granulopoiesis and down regulated during erythropoiesis. Megakaryopoitic differentiation resulted in significant alteration in the expression of many miRNAs that are believed to play critical roles in the regulation of B and T cell differentiation. Target prediction analyses on three different miRNA databases indicated that TargetScan outperformed microCosm and miRDB in identifying potential miRNA targets associated with hematopoietic differentiation process. An integrated analysis of the observed miRNAs and messenger RNAs (mRNAs) resulted in 87 highly correlated miRNA-mRNA pairs that have major functional roles in cellular growth and proliferation, hematopoietic system development, and Wnt/B-catenin and Flt 3 signaling pathways. We believe that this study will enhance our understanding on the regulatory roles of miRNA in hematopoiesis by providing a library of mRNA-miRNA networks.

  17. Agile Metrics: Progress Monitoring of Agile Contractors

    DTIC Science & Technology

    2014-01-01

    can be tailored to leverage the iterative nature of Agile meth- ods. Using optional contract funding lines or indefinite delivery indefinite quantity... naturally created during the execution of the Agile implementation. In the following paragraphs, we identify issues to consider in building an Agile...employing Agile methods [Hartman 2006]. Be prepared to mine and effectively use the metrics data that naturally occur in typical Ag- ile teams. In

  18. Arctigenin Confers Neuroprotection Against Mechanical Trauma Injury in Human Neuroblastoma SH-SY5Y Cells by Regulating miRNA-16 and miRNA-199a Expression to Alleviate Inflammation.

    PubMed

    Song, Jie; Li, Na; Xia, Yang; Gao, Zhong; Zou, Sa-Feng; Yan, Yu-Hui; Li, Shao-Heng; Wang, Yue; Meng, Ya-Kun; Yang, Jing-Xian; Kang, Ting-Guo

    2016-09-01

    Mechanical trauma injury is a severe insult to neural cells. Subsequent secondary injury involves the release of inflammatory factors that have dramatic consequences for undamaged cells, leading to normal cell death after the initial injury. The present study investigated the capacity for arctigenin (ARC) to prevent secondary effects and evaluated the mechanism underlying the action of microRNA (miRNA)-199a and miRNA-16 in a mechanical trauma injury (MTI) model using SH-SY5Y cells in vitro. SH-SY5Y cells are often applied to in vitro models of neuronal function and differentiation. Recently, miRNAs have been demonstrated to play a crucial role in NF-κB and cholinergic signaling, which can regulate inflammation. The cell model was established by scratch-induced injury of human SH-SY5Y cells, which mimics the characteristics of MTI. A cell counting kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunocytochemistry were used to measure cell viability. Enzyme-linked immunosorbent assay (ELISA) was used to evaluate the inflammatory cytokine and cholinesterase (CHE) content. The lactate dehydrogenase (LDH) content was measured to assess the degree of cell injury. The mRNA levels were measured by RT-PCR to analyze ARC's mechanism of action. miRNA inhibitors and mimics were used to inhibit and strengthen the expression of miRNAs. Protein expression was detected by western blotting analysis. ARC treatment reduced the TNF-α and IL-6 levels as well as the number of TUNEL+ apoptotic SH-SY5Y cells surrounding the scratch and increased the IL-10 level compared to the controls. ARC attenuated the increase of the cell damage degree and LDH content induced by scratching, indicating increased cell survival. Mechanistic studies showed that ARC upregulated the miRNA-16 and miRNA-199a levels to reduce upstream protein (IKKα and IKKβ) expression and inhibit NF-κB signaling pathway activity; moreover, the increased miRNA-199a suppresses

  19. Comparison of hepatocellular carcinoma miRNA expression profiling as evaluated by next generation sequencing and microarray.

    PubMed

    Murakami, Yoshiki; Tanahashi, Toshihito; Okada, Rina; Toyoda, Hidenori; Kumada, Takashi; Enomoto, Masaru; Tamori, Akihiro; Kawada, Norifumi; Taguchi, Y-h; Azuma, Takeshi

    2014-01-01

    MicroRNA (miRNA) expression profiling has proven useful in diagnosing and understanding the development and progression of several diseases. Microarray is the standard method for analyzing miRNA expression profiles; however, it has several disadvantages, including its limited detection of miRNAs. In recent years, advances in genome sequencing have led to the development of next-generation sequencing (NGS) technologies, which significantly advance genome sequencing speed and discovery. In this study, we compared the expression profiles obtained by next generation sequencing (NGS) with the profiles created using microarray to assess if NGS could produce a more accurate and complete miRNA profile. Total RNA from 14 hepatocellular carcinoma tumors (HCC) and 6 matched non-tumor control tissues were sequenced with Illumina MiSeq 50-bp single-end reads. Micro RNA expression profiles were estimated using miRDeep2 software. As a comparison, miRNA expression profiles for 11 out of 14 HCCs were also established by microarray (Agilent human microRNA microarray). The average total sequencing exceeded 2.2 million reads per sample and of those reads, approximately 57% mapped to the human genome. The average correlation for miRNA expression between microarray and NGS and subtraction were 0.613 and 0.587, respectively, while miRNA expression between technical replicates was 0.976. The diagnostic accuracy of HCC, p-value, and AUC were 90.0%, 7.22×10(-4), and 0.92, respectively. In summary, NGS created an miRNA expression profile that was reproducible and comparable to that produced by microarray. Moreover, NGS discovered novel miRNAs that were otherwise undetectable by microarray. We believe that miRNA expression profiling by NGS can be a useful diagnostic tool applicable to multiple fields of medicine.

  20. Identification of miRNAs differentially expressed in human epilepsy with or without granule cell pathology.

    PubMed

    Zucchini, Silvia; Marucci, Gianluca; Paradiso, Beatrice; Lanza, Giovanni; Roncon, Paolo; Cifelli, Pierangelo; Ferracin, Manuela; Giulioni, Marco; Michelucci, Roberto; Rubboli, Guido; Simonato, Michele

    2014-01-01

    The microRNAs (miRNAs) are small size non-coding RNAs that regulate expression of target mRNAs at post-transcriptional level. miRNAs differentially expressed under pathological conditions may help identifying mechanisms underlying the disease and may represent biomarkers with prognostic value. However, this kind of studies are difficult in the brain because of the cellular heterogeneity of the tissue and of the limited access to fresh tissue. Here, we focused on a pathology affecting specific cells in a subpopulation of epileptic brains (hippocampal granule cells), an approach that bypasses the above problems. All patients underwent surgery for intractable temporal lobe epilepsy and had hippocampal sclerosis associated with no granule cell pathology in half of the cases and with type-2 granule cell pathology (granule cell layer dispersion or bilamination) in the other half. The expression of more than 1000 miRNAs was examined in the laser-microdissected dentate granule cell layer. Twelve miRNAs were differentially expressed in the two groups. One of these, miR487a, was confirmed to be expressed at highly differential levels in an extended cohort of patients, using RT-qPCR. Bioinformatics searches and RT-qPCR verification identified ANTXR1 as a possible target of miR487a. ANTXR1 may be directly implicated in granule cell dispersion because it is an adhesion molecule that favors cell spreading. Thus, miR487a could be the first identified element of a miRNA signature that may be useful for prognostic evaluation of post-surgical epilepsy and may drive mechanistic studies leading to the identification of therapeutic targets.

  1. Inhibition of SW620 human colon cancer cells by upregulating miRNA-145

    PubMed Central

    Li, Chen; Xu, Na; Li, Yu-Qiang; Wang, Yu; Zhu, Zhi-Tu

    2016-01-01

    AIM: To investigate the targeted inhibition of proliferation and migration of SW620 human colon cancer cells by upregulating miRNA-145 (miR-145). METHODS: Forty-five samples of colon cancer tissues and 45 normal control samples were obtained from the biological database of the First Affiliated Hospital of Liaoning Medical University. We performed quantitative analysis of miR-145 and N-ras expression in tissues; reverse transcriptase polymerase chain reaction analysis of miR-145 expression in SW620 colon cancer cells and normal colonic epithelial cells; construction of miR-145 lentiviral vector and determination of miR-145 expression in SW620 cells transduced with miR-145 vector; analysis of the effect of miR-145 overexpression on SW620 cell proliferation; analysis of the effect of miR-145 overexpression on SW620 cell migration using a wound healing assay; and analysis of the effect of miR-145 on N-ras expression using Western blotting. RESULTS: miR-145 expression was significantly downregulated in colon cancer tissues, with its expression in normal colonic tissues being 4-5-fold higher (two sample t test, P < 0.05), whereas N-ras expression showed the opposite trend. miR-145 expression in SW620 cells was downregulated, which was significantly lower compared to that in colonic epithelial cells (two sample t test, P < 0.05). miR-145 vector and control were successfully packaged; expression of miR-145 in SW620 cells transduced with miR-145 was 8.2-fold of that in control cells (two sample t test, P < 0.05). The proliferation of miR-145-transduced SW620 cells was significantly decreased compared to control cells (two sample t test, P < 0.05). At 48 h in the wound healing experiment, the migration indexes and controls were (97.27% ± 9.25%) and (70.22% ± 6.53%), respectively (two sample t test, P < 0.05). N-ras expression in miR-145-tranduced SW620 cells was significantly lower than others (one-way analysis of variance, P < 0.05). CONCLUSION: miR-145 is important in

  2. The human DiGeorge syndrome critical region gene 8 and Its D. melanogaster homolog are required for miRNA biogenesis.

    PubMed

    Landthaler, Markus; Yalcin, Abdullah; Tuschl, Thomas

    2004-12-14

    MicroRNAs (miRNAs) represent a family of small noncoding RNAs that are found in plants and animals (for recent reviews, see ). miRNAs are expressed in a developmentally and tissue-specific manner and regulate the translational efficiency and stability of partial or fully sequence-complementary mRNAs. miRNAs are excised in a stepwise process from double-stranded RNA precursors that are embedded in long RNA polymerase II primary transcripts (pri-miRNA). Drosha RNase III catalyzes the first excision event, the release in the nucleus of a hairpin RNA (pre-miRNA), which is followed by export of the pre-miRNA to the cytoplasm and further processing by Dicer to mature miRNAs. Here, we characterize the human DGCR8, the DiGeorge syndrome critical region gene 8, and its Drosophila melanogaster homolog. We provide biochemical and cell-based readouts to demonstrate the requirement of DGCR8 for the maturation of miRNA primary transcripts. RNAi knockdown experiments of fly and human DGCR8 resulted in accumulation of pri-miRNAs and reduction of pre-miRNAs and mature miRNAs. Our results suggest that DGCR8 and Drosha interact in human cells and reside in a functional pri-miRNA processing complex.

  3. Telomere Length, TERT, and miRNA Expression

    PubMed Central

    Slattery, Martha L.; Herrick, Jennifer S.; Pellatt, Andrew J.; Wolff, Roger K.; Mullany, Lila E.

    2016-01-01

    It has been proposed that miRNAs are involved in the control of telomeres. We test that hypothesis by examining the association between miRNAs and telomere length (TL). Additionally, we evaluate if genetic variation in telomerase reverse transcriptase (TERT) is associated with miRNA expression levels. We use data from a population-based study of colorectal cancer (CRC), where we have previously shown associations between TL and TERT and CRC, to test associations between TL and miRNA expression and TERT and miRNA expression. To gain insight into functions of miRNAs associated with TERT we tested linear associations between miRNAs and their targeted gene mRNAs. An Agilent platform that contained information on over 2000 miRNAs was used. TL was measured using a multiplexed quantitative PCR (qPCR). RNAseq was used to assess gene expression. Our sample consisted of 1152 individuals with SNP data and miRNA expression data; 363 individuals with both TL and miRNA; and 148 individuals with miRNA and mRNA data. Thirty-three miRNAs were directly associated with TL after adjusting for age and sex (false discovery rate (FDR) of 0.05). TERT rs2736118 was associated with differences in miRNA expression between carcinoma and normal colonic mucosa for 75 miRNAs (FDR <0.05). Genes regulated by these miRNAs, as indicated by mRNA/miRNA associations, were associated with major signaling pathways beyond their TL-related functions, including PTEN, and PI3K/AKT signaling. Our data support a direct association between miRNAs and TL; differences in miRNA expression levels by TERT genotype were observed. Based on miRNA and targeted mRNA associations our data suggest that TERT is involved in non-TL-related functions by acting through altered miRNA expression. PMID:27627813

  4. A path-based measurement for human miRNA functional similarities using miRNA-disease associations

    NASA Astrophysics Data System (ADS)

    Ding, Pingjian; Luo, Jiawei; Xiao, Qiu; Chen, Xiangtao

    2016-09-01

    Compared with the sequence and expression similarity, miRNA functional similarity is so important for biology researches and many applications such as miRNA clustering, miRNA function prediction, miRNA synergism identification and disease miRNA prioritization. However, the existing methods always utilized the predicted miRNA target which has high false positive and false negative to calculate the miRNA functional similarity. Meanwhile, it is difficult to achieve high reliability of miRNA functional similarity with miRNA-disease associations. Therefore, it is increasingly needed to improve the measurement of miRNA functional similarity. In this study, we develop a novel path-based calculation method of miRNA functional similarity based on miRNA-disease associations, called MFSP. Compared with other methods, our method obtains higher average functional similarity of intra-family and intra-cluster selected groups. Meanwhile, the lower average functional similarity of inter-family and inter-cluster miRNA pair is obtained. In addition, the smaller p-value is achieved, while applying Wilcoxon rank-sum test and Kruskal-Wallis test to different miRNA groups. The relationship between miRNA functional similarity and other information sources is exhibited. Furthermore, the constructed miRNA functional network based on MFSP is a scale-free and small-world network. Moreover, the higher AUC for miRNA-disease prediction indicates the ability of MFSP uncovering miRNA functional similarity.

  5. MiRNA-320 in the human follicular fluid is associated with embryo quality in vivo and affects mouse embryonic development in vitro.

    PubMed

    Feng, Ruizhi; Sang, Qing; Zhu, Yan; Fu, Wei; Liu, Miao; Xu, Yan; Shi, Huijuan; Xu, Yao; Qu, Ronggui; Chai, Renjie; Shao, Ruijin; Jin, Li; He, Lin; Sun, Xiaoxi; Wang, Lei

    2015-03-03

    Previous work from our laboratory demonstrated the existence of miRNAs in human follicular fluid. In the current study, we have sought to identify miRNAs that might affect oocyte/embryo quality in patients undergoing intracytoplasmic sperm injection and to investigate their roles in in vitro fertilization outcomes in mouse oocytes. 53 samples were classified as Group 1 (high quality) if the day-3 embryos had seven and more cells or as Group 2 (low quality) if the embryos had six and fewer cells. TaqMan Human microRNAs cards and qRT-PCR were performed to verify differently expressed miRNAs. The function of the corresponding miRNA was investigated in mouse oocytes by injecting them with miRNA-inhibitor oligonucleotides. We found that hsa-miR-320a and hsa-miR-197 had significantly higher expression levels in the Group 1 follicular fluids than in Group 2 (p = 0.0073 and p = 0.008, respectively). Knockdown of mmu-miR-320 in mouse oocytes strongly decreased the proportions of MII oocytes that developed into two-cell and blastocyst stage embryos (p = 0.0048 and p = 0.0069, respectively). Wnt signaling pathway components had abnormal expression level in miR-320 inhibitor-injected oocytes. This study provides the first evidence that miRNAs in human follicular fluid are indicative of and can influence embryo quality.

  6. S6K2-mediated regulation of TRBP as a determinant of miRNA expression in human primary lymphatic endothelial cells.

    PubMed

    Warner, Matthew J; Bridge, Katherine S; Hewitson, James P; Hodgkinson, Michael R; Heyam, Alex; Massa, Bailey C; Haslam, Jessica C; Chatzifrangkeskou, Maria; Evans, Gareth J O; Plevin, Michael J; Sharp, Tyson V; Lagos, Dimitris

    2016-11-16

    MicroRNAs (miRNAs) are short non-coding RNAs that silence mRNAs. They are generated following transcription and cleavage by the DROSHA/DGCR8 and DICER/TRBP/PACT complexes. Although it is known that components of the miRNA biogenesis machinery can be phosphorylated, it remains poorly understood how these events become engaged during physiological cellular activation. We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. We demonstrate the functional relevance of this interaction in primary human dermal lymphatic endothelial cells (HDLECs). Angiopoietin-1 (ANG1) can augment miRNA biogenesis in HDLECs through enhancing TRBP phosphorylation and expression in an S6K2-dependent manner. We propose that the S6K2/TRBP node controls miRNA biogenesis in HDLECs and provides a molecular link between the mTOR pathway and the miRNA biogenesis machinery.

  7. S6K2-mediated regulation of TRBP as a determinant of miRNA expression in human primary lymphatic endothelial cells

    PubMed Central

    Warner, Matthew J.; Bridge, Katherine S.; Hewitson, James P.; Hodgkinson, Michael R.; Heyam, Alex; Massa, Bailey C.; Haslam, Jessica C.; Chatzifrangkeskou, Maria; Evans, Gareth J.O.; Plevin, Michael J.; Sharp, Tyson V.; Lagos, Dimitris

    2016-01-01

    MicroRNAs (miRNAs) are short non-coding RNAs that silence mRNAs. They are generated following transcription and cleavage by the DROSHA/DGCR8 and DICER/TRBP/PACT complexes. Although it is known that components of the miRNA biogenesis machinery can be phosphorylated, it remains poorly understood how these events become engaged during physiological cellular activation. We demonstrate that S6 kinases can phosphorylate the extended C-terminal domain of TRBP and interact with TRBP in situ in primary cells. TRBP serines 283/286 are essential for S6K-mediated TRBP phosphorylation, optimal expression of TRBP, and the S6K-TRBP interaction in human primary cells. We demonstrate the functional relevance of this interaction in primary human dermal lymphatic endothelial cells (HDLECs). Angiopoietin-1 (ANG1) can augment miRNA biogenesis in HDLECs through enhancing TRBP phosphorylation and expression in an S6K2-dependent manner. We propose that the S6K2/TRBP node controls miRNA biogenesis in HDLECs and provides a molecular link between the mTOR pathway and the miRNA biogenesis machinery. PMID:27407113

  8. Agility Quotient (AQ)

    DTIC Science & Technology

    2014-06-01

    system?s Agility IQ ?? and ?What is the requisite amount of Agility that is required?? This paper suggests a way forward and illustrates it, in the...answer two questions. “How can we measure a system’s Agility IQ ?” and “What is the requisite amount of Agility that is required?” This paper...agility is worth our attention. AQ can be patterned after the Intelligence Quotient ( IQ ). IQ is a score that is associated with educational potential

  9. The onset of human ectopic pregnancy demonstrates a differential expression of miRNAs and their cognate targets in the Fallopian tube.

    PubMed

    Feng, Yi; Zou, Shien; Weijdegård, Birgitta; Chen, Jie; Cong, Qing; Fernandez-Rodriguez, Julia; Wang, Lei; Billig, Håkan; Shao, Ruijin

    2014-01-01

    Human ectopic pregnancy (EP) is a leading cause of pregnancy-related death, but the molecular basis underlying the onset of tubal EP is largely unknown. Female Dicer1 conditional knockout mice are infertile with dysfunctional Fallopian tube and have a different miRNA expression profile compared to wild-type mice, and we speculated that Dicer-mediated regulation of miRNA expression and specific miRNA-controlled targets might contribute to the onset of tubal EP. In the present study, we used microarray analysis and quantitative RT-PCR to examine the expression of miRNAs and core miRNA regulatory components in Fallopian tube tissues from women with EP. We found that the levels of DICER1, four miRNAs (let-7i, miR-149, miR-182, and miR-424), and estrogen receptor α distinguished the tubal implantation site from the non-implantation site. Computational algorithms and screening for interactions with the estrogen and progesterone receptor signaling pathways showed that the four miRNAs were predicted to target ten genes, including NEDD4, TAF15, and SPEN. Subsequent experiments showed differences in NEDD4 mRNA and protein levels between the implantation and non-implantation sites. Finally, we revealed that increases in smooth muscle cell NEDD4 and stromal cell TAF15, in parallel with a decrease in epithelial cell SPEN, were associated with tubal implantation. Our study suggests that changes in miRNA levels by the DICER-mediated miRNA-processing machinery result in aberrant expression of cell type-specific proteins that are potentially involved in the onset of tubal EP.

  10. Discovery and characterization of miRNA during cellular senescence in bone marrow-derived human mesenchymal stem cells.

    PubMed

    Yoo, Jung Ki; Kim, Chang-Hyun; Jung, Ho Yong; Lee, Dong Ryul; Kim, Jin Kyeoung

    2014-10-01

    Cellular senescence is an irreversible cell cycle arrest in which specific mRNAs and miRNAs are involved in senescence progression. miRNAs interact with specific mRNAs to regulate various cellular mechanisms, including metabolism, proliferation, apoptosis, senescence and differentiation. In this study, we identify and characterize miRNAs during cellular senescence in mesenchymal stem cells (MSCs). Using previously reported miRNAs, expression profiling of 23 miRNAs was performed using real-time PCR analysis. Among these miRNAs, 19 miRNAs showed upregulated expression patterns in senescent MSCs compared with young MSCs, and 5 miRNAs were downregulated. These miRNAs have not been previously identified as being related to cellular senescence but seem to be related. miR-103-2*, miR-140-5p and miR-330-5p are highly upregulated, while miR-29b and miR-199b-5p are significantly downregulated in senescent MSCs. We identify unique functions of 5 miRNAs and predict putative target genes of 5 miRNAs using our previous report. Among them, miR-199b-5p directly suppressed LAMC1 expression, as shown in a luciferase assay. miR-199b-5p significantly regulates translational activity but does not control post-transcriptional activity. Likewise, miR-199b-5p modulates LAMC networks, which demonstrates the resulting phenomenon during cellular senescence, namely, that miR-199b-5p indirectly regulates cellular senescence in MSCs.

  11. Human Lin28 Forms a High-Affinity 1:1 Complex with the 106~363 Cluster miRNA miR-363

    PubMed Central

    2016-01-01

    Lin28A is a post-transcriptional regulator of gene expression that interacts with and negatively regulates the biogenesis of let-7 family miRNAs. Recent data suggested that Lin28A also binds the putative tumor suppressor miR-363, a member of the 106~363 cluster of miRNAs. Affinity for this miRNA and the stoichiometry of the protein–RNA complex are unknown. Characterization of human Lin28’s interaction with RNA has been complicated by difficulties in producing stable RNA-free protein. We have engineered a maltose binding protein fusion with Lin28, which binds let-7 miRNA with a Kd of 54.1 ± 4.2 nM, in agreement with previous data on a murine homologue. We show that human Lin28A binds miR-363 with a 1:1 stoichiometry and with a similar, if not higher, affinity (Kd = 16.6 ± 1.9 nM). Further analysis suggests that the interaction of the N-terminal cold shock domain of Lin28A with RNA is salt-dependent, supporting a model in which the cold shock domain allows the protein to sample RNA substrates through transient electrostatic interactions. PMID:27559824

  12. Decision Science Challenges for C2 Agility

    DTIC Science & Technology

    2014-06-01

    Controlled and automatic human information processing: II. Perceptual learning , automatic attending and a general theory . Psychological Review, 84 (2...1 19 th ICCRTS “C2 Agility: Lessons Learned from Research and Operations” Decision Science Challenges for C2 Agility Topic 1 (First...systems. We have two vectors there. The first vector would be in things like man-machine interface. The second ... is in the whole area of cognition

  13. Regulation of neurotropic signaling by the inducible, NF-kB-sensitive miRNA-125b in Alzheimer's disease (AD) and in primary human neuronal-glial (HNG) cells.

    PubMed

    Zhao, Yuhai; Bhattacharjee, Surjyadipta; Jones, Brandon M; Hill, Jim; Dua, Prerna; Lukiw, Walter J

    2014-08-01

    Inducible microRNAs (miRNAs) perform critical regulatory roles in central nervous system (CNS) development, aging, health, and disease. Using miRNA arrays, RNA sequencing, enhanced Northern dot blot hybridization technologies, Western immunoblot, and bioinformatics analysis, we have studied miRNA abundance and complexity in Alzheimer's disease (AD) brain tissues compared to age-matched controls. In both short post-mortem AD and in stressed primary human neuronal-glial (HNG) cells, we observe a consistent up-regulation of several brain-enriched miRNAs that are under transcriptional control by the pro-inflammatory transcription factor NF-kB. These include miRNA-9, miRNA-34a, miRNA-125b, miRNA-146a, and miRNA-155. Of the inducible miRNAs in this subfamily, miRNA-125b is among the most abundant and significantly induced miRNA species in human brain cells and tissues. Bioinformatics analysis indicated that an up-regulated miRNA-125b could potentially target the 3'untranslated region (3'-UTR) of the messenger RNA (mRNA) encoding (a) a 15-lipoxygenase (15-LOX; ALOX15; chr 17p13.3), utilized in the conversion of docosahexaneoic acid into neuroprotectin D1 (NPD1), and (b) the vitamin D3 receptor (VDR; VD3R; chr12q13.11) of the nuclear hormone receptor superfamily. 15-LOX and VDR are key neuromolecular factors essential in lipid-mediated signaling, neurotrophic support, defense against reactive oxygen and nitrogen species (reactive oxygen and nitrogen species), and neuroprotection in the CNS. Pathogenic effects appear to be mediated via specific interaction of miRNA-125b with the 3'-UTR region of the 15-LOX and VDR messenger RNAs (mRNAs). In AD hippocampal CA1 and in stressed HNG cells, 15-LOX and VDR down-regulation and a deficiency in neurotrophic support may therefore be explained by the actions of a single inducible, pro-inflammatory miRNA-125b. We will review the recent data on the pathogenic actions of this up-regulated miRNA-125b in AD and discuss potential

  14. Agile Software Development

    ERIC Educational Resources Information Center

    Biju, Soly Mathew

    2008-01-01

    Many software development firms are now adopting the agile software development method. This method involves the customer at every level of software development, thus reducing the impact of change in the requirement at a later stage. In this article, the principles of the agile method for software development are explored and there is a focus on…

  15. Clean, Agile Processing Technology.

    DTIC Science & Technology

    1997-12-01

    Research ltr dtd 10 Jun 98 THIS PAGE IS UNCLASSIFIED FINAL REPORT CLEAN, AGILE PROCESSING TECHNOLOGY Contract # N00014-96-C-0139 PI: S. W . Sinton...Agile Processing Technology . T UNCLAS I N Sinton, S. W.IN S REQUIRED FOR (Explain needin detaiO E C This document is requested by the Canadian Department

  16. Markov State Models Reveal a Two-Step Mechanism of miRNA Loading into the Human Argonaute Protein: Selective Binding followed by Structural Re-arrangement

    PubMed Central

    Jiang, Hanlun; Sheong, Fu Kit; Zhu, Lizhe; Gao, Xin; Bernauer, Julie; Huang, Xuhui

    2015-01-01

    Argonaute (Ago) proteins and microRNAs (miRNAs) are central components in RNA interference, which is a key cellular mechanism for sequence-specific gene silencing. Despite intensive studies, molecular mechanisms of how Ago recognizes miRNA remain largely elusive. In this study, we propose a two-step mechanism for this molecular recognition: selective binding followed by structural re-arrangement. Our model is based on the results of a combination of Markov State Models (MSMs), large-scale protein-RNA docking, and molecular dynamics (MD) simulations. Using MSMs, we identify an open state of apo human Ago-2 in fast equilibrium with partially open and closed states. Conformations in this open state are distinguished by their largely exposed binding grooves that can geometrically accommodate miRNA as indicated in our protein-RNA docking studies. miRNA may then selectively bind to these open conformations. Upon the initial binding, the complex may perform further structural re-arrangement as shown in our MD simulations and eventually reach the stable binary complex structure. Our results provide novel insights in Ago-miRNA recognition mechanisms and our methodology holds great potential to be widely applied in the studies of other important molecular recognition systems. PMID:26181723

  17. Selection of reference genes is critical for miRNA expression analysis in human cardiac tissue. A focus on atrial fibrillation

    PubMed Central

    Masè, Michela; Grasso, Margherita; Avogaro, Laura; D’Amato, Elvira; Tessarolo, Francesco; Graffigna, Angelo; Denti, Michela Alessandra; Ravelli, Flavia

    2017-01-01

    MicroRNAs (miRNAs) are emerging as key regulators of complex biological processes in several cardiovascular diseases, including atrial fibrillation (AF). Reverse transcription-quantitative polymerase chain reaction is a powerful technique to quantitatively assess miRNA expression profile, but reliable results depend on proper data normalization by suitable reference genes. Despite the increasing number of studies assessing miRNAs in cardiac disease, no consensus on the best reference genes has been reached. This work aims to assess reference genes stability in human cardiac tissue with a focus on AF investigation. We evaluated the stability of five reference genes (U6, SNORD48, SNORD44, miR-16, and 5S) in atrial tissue samples from eighteen cardiac-surgery patients in sinus rhythm and AF. Stability was quantified by combining BestKeeper, delta-Cq, GeNorm, and NormFinder statistical tools. All methods assessed SNORD48 as the best and U6 as the worst reference gene. Applications of different normalization strategies significantly impacted miRNA expression profiles in the study population. Our results point out the necessity of a consensus on data normalization in AF studies to avoid the emergence of divergent biological conclusions. PMID:28117343

  18. From target therapy to miRNA therapeutics of human multiple myeloma: theoretical and technological issues in the evolving scenario.

    PubMed

    Rossi, Marco; Amodio, Nicola; Di Martino, M T; Caracciolo, Daniele; Tagliaferri, Pierosandro; Tassone, Pierfrancesco

    2013-09-01

    The progress in the understanding of biological events underlying multiple myeloma (MM) development and progression has allowed the design of molecularly targeted therapies (MTTs) for this disease and several new compounds are presently under investigation in the preclinical and clinical settings. The recent discovery that miRNAs, and short non coding RNAs in general, are involved in the pathogenesis of cancer has raised the issue whether a novel therapeutic approach should be provided by selective interference with miRNA network. This review will focus on the rationale of miRNA-based therapeutics, providing the most relevant information on biogenesis and technical issues in miRNA analysis. Finally, a detailed overview of the recent findings on miRNA therapeutics of MM will be discussed.

  19. Focused Logistics: Putting Agility in Agile Logistics

    DTIC Science & Technology

    2011-05-19

    envisioned an agile and adaptable logstics system built around common situational understanding.5 The Focused Logistics concept specified the requirement to...the tracking of resources moving through the TD network. As a result, 112 Ibid, 20. 113 Ibid, 18-20. 39 distribution centers tagged inbound

  20. Circulating plant miRNAs can regulate human gene expression in vitro

    PubMed Central

    Pastrello, Chiara; Tsay, Mike; McQuaid, Rosanne; Abovsky, Mark; Pasini, Elisa; Shirdel, Elize; Angeli, Marc; Tokar, Tomas; Jamnik, Joseph; Kotlyar, Max; Jurisicova, Andrea; Kotsopoulos, Joanne; El-Sohemy, Ahmed; Jurisica, Igor

    2016-01-01

    While Brassica oleracea vegetables have been linked to cancer prevention, the exact mechanism remains unknown. Regulation of gene expression by cross-species microRNAs has been previously reported; however, its link to cancer suppression remains unexplored. In this study we address both issues. We confirm plant microRNAs in human blood in a large nutrigenomics study cohort and in a randomized dose-controlled trial, finding a significant positive correlation between the daily amount of broccoli consumed and the amount of microRNA in the blood. We also demonstrate that Brassica microRNAs regulate expression of human genes and proteins in vitro, and that microRNAs cooperate with other Brassica-specific compounds in a possible cancer-preventive mechanism. Combined, we provide strong evidence and a possible multimodal mechanism for broccoli in cancer prevention. PMID:27604570

  1. Cross-Analysis of Gene and miRNA Genome-Wide Expression Profiles in Human Fibroblasts at Different Stages of Transformation

    PubMed Central

    Ostano, Paola; Bione, Silvia; Belgiovine, Cristina; Chiodi, Ilaria; Ghimenti, Chiara; Scovassi, A. Ivana; Chiorino, Giovanna

    2012-01-01

    Abstract We have developed a cellular system constituted of human telomerase immortalized fibroblasts that gradually underwent neoplastic transformation during propagation in culture. We exploited this cellular system to investigate gene and miRNA transcriptional programs in cells at different stages of propagation, representing five different phases along the road to transformation, from non-transformed cells up to tumorigenic and metastatic ones. Here we show that gene and miRNA expression profiles were both able to divide cells according to their transformation phase. We identified more than 1,700 genes whose expression was highly modulated in cells at at least one propagation stage and we found that the number of modulated genes progressively increased at successive stages of transformation. These genes identified processes significantly deregulated in tumorigenic cells, such as cell differentiation, cell movement and extracellular matrix remodeling, cell cycle and apoptosis, together with upregulation of several cancer testis antigens. Alterations in cell cycle, apoptosis, and cancer testis antigen expression were particular hallmarks of metastatic cells. A parallel deregulation of a panel of 43 miRNAs strictly connected to the p53 and c-Myc pathways and with oncogenic/oncosuppressive functions was also found. Our results indicate that cen3tel cells can be a useful model for human fibroblast neoplastic transformation, which appears characterized by complex and peculiar alterations involving both genetic and epigenetic reprogramming, whose elucidation could provide useful insights into regulatory networks underlying cancerogenesis. PMID:22321013

  2. Cross-analysis of gene and miRNA genome-wide expression profiles in human fibroblasts at different stages of transformation.

    PubMed

    Ostano, Paola; Bione, Silvia; Belgiovine, Cristina; Chiodi, Ilaria; Ghimenti, Chiara; Scovassi, A Ivana; Chiorino, Giovanna; Mondello, Chiara

    2012-01-01

    We have developed a cellular system constituted of human telomerase immortalized fibroblasts that gradually underwent neoplastic transformation during propagation in culture. We exploited this cellular system to investigate gene and miRNA transcriptional programs in cells at different stages of propagation, representing five different phases along the road to transformation, from non-transformed cells up to tumorigenic and metastatic ones. Here we show that gene and miRNA expression profiles were both able to divide cells according to their transformation phase. We identified more than 1,700 genes whose expression was highly modulated in cells at at least one propagation stage and we found that the number of modulated genes progressively increased at successive stages of transformation. These genes identified processes significantly deregulated in tumorigenic cells, such as cell differentiation, cell movement and extracellular matrix remodeling, cell cycle and apoptosis, together with upregulation of several cancer testis antigens. Alterations in cell cycle, apoptosis, and cancer testis antigen expression were particular hallmarks of metastatic cells. A parallel deregulation of a panel of 43 miRNAs strictly connected to the p53 and c-Myc pathways and with oncogenic/oncosuppressive functions was also found. Our results indicate that cen3tel cells can be a useful model for human fibroblast neoplastic transformation, which appears characterized by complex and peculiar alterations involving both genetic and epigenetic reprogramming, whose elucidation could provide useful insights into regulatory networks underlying cancerogenesis.

  3. Distinct microRNA expression signatures in human right atrial and ventricular myocardium.

    PubMed

    Zhang, Yangyang; Wang, Xiaowei; Xu, Xiaohan; Wang, Jun; Liu, Xiang; Chen, Yijiang

    2012-12-01

    Human atrial and ventricular myocardium has distinct structure and physiology. MicroRNAs (miRNAs) are the central players in the regulation of gene expression, participating in many physiological processes. A comprehensive knowledge of miRNA expression in the human heart is essential for the understanding of myocardial function. The aim of this study was to compare the miRNA signature in human right atrial and ventricular myocardium. Agilent human miRNA arrays were used to indicate the miRNA expression signatures of the right atrial (n = 8) and ventricular (n = 9) myocardium of healthy individuals. Quantitative reverse transcription-polymerase chain reactions (qRT-PCRs) were used to validate the array results. DIANA-mirPath was used to incorporate the miRNAs into pathways. MiRNA arrays showed that 169 miRNAs were expressed at different levels in human right atrial and ventricular myocardium. The unsupervised hierarchical clustering analysis based on the 169 dysregulated miRNAs showed that miRNA expression categorized two well-defined clusters that corresponded to human right atrial and ventricular myocardium. The qRT-PCR results correlated well with the microarray data. Bioinformatic analysis indicated the potential miRNA targets and molecular pathways. This study indicates that distinct miRNA expression signatures in human right atrial and ventricular myocardium. The findings provide a novel understanding of the molecular differences between human atrial and ventricular myocardium and may establish a framework for an anatomically detailed evaluation of cardiac function regulation.

  4. Regulation of miRNA Processing and miRNA Mediated Gene Repression in Cancer

    PubMed Central

    Bajan, Sarah; Hutvagner, Gyorgy

    2014-01-01

    The majority of human protein-coding genes are predicted to be targets of miRNA-mediated post-transcriptional regulation. The widespread influence of miRNAs is illustrated by their essential roles in all biological processes. Regulated miRNA expression is essential for maintaining cellular differentiation; therefore alterations in miRNA expression patterns are associated with several diseases, including various cancers. High-throughput sequencing technologies revealed low level expressing miRNA isoforms, termed isomiRs. IsomiRs may differ in sequence, length, target preference and expression patterns from their parental miRNA and can arise from differences in miRNA biosynthesis, RNA editing, or SNPs inherent to the miRNA gene. The association between isomiR expression and disease progression is largely unknown. Misregulated miRNA expression is thought to contribute to the formation and/or progression of cancer. However, due to the diversity of targeted transcripts, miRNAs can function as both tumor-suppressor genes and oncogenes as defined by cellular context. Despite this, miRNA profiling studies concluded that the differential expression of particular miRNAs in diseased tissue could aid the diagnosis and treatment of some cancers. PMID:25069508

  5. An agile implementation of SCRUM

    NASA Astrophysics Data System (ADS)

    Gannon, Michele

    Is Agile a way to cut corners? To some, the use of an Agile Software Development Methodology has a negative connotation - “ Oh, you're just not producing any documentation” . So can a team with no experience in Agile successfully implement and use SCRUM?

  6. The expression of miRNA-221 and miRNA-222 in gliomas patients and their prognosis.

    PubMed

    Xue, Liang; Wang, Yi; Yue, Shuyuan; Zhang, Jianning

    2017-01-01

    The aim of this study is to explore the expression of microRNA (miRNA)-221 and miRNA-222 in human glioma cells and tissues. The expression of miRNA-221 and miRNA-222 in human glioma cell line U87, U251, A172, LN229 and surgery resected glioma tissues were measured. The survival rate of X-ray (2 Gy) irradiated glioma cells were calculated. 165 cases of glioma patients were recruited successfully; the expression of miRNA-221 and miRNA-222 in their resected tissues were measured. The expression of miRNA-221 and miRNA-222 in cancer tissues were obviously higher than control tissues (normal brain tissue) and control cell (gastric mucosal epithelial cell, GES) (p < 0.05). The highly malignant glioma tissues expressed significantly higher miRNA-221 and miRNA-222 than low malignant glioma tissues. Patients with highly expressed miRNA-221 and miRNA-222 have shorter survival time. Survival rate of glioma cells was significantly higher than GES cell after irradiation (p < 0.05); miRNA-221 in glioma cells. The expressions of miRNA-221 and miRNA-222 in irritated glioma cells were positively correlated with the survival rate of glioma cells (r = 0.629, 0.712, both p < 0.01). For the 165 glioma patients, the expressions of miRNA-221 and miRNA-222 increased with the increasing of pathological grades (χ (2) = 42.85, p < 0.01); and their survival time decreased when miRNA-221 expression elevated (χ (2) = 57.12, p < 0.01). MiRNA-221 and miRNA-222 express highly in human glioma cells and tissues. Expression of miRNA-221 and miRNA-222 are closely related to pathological grading and prognosis of glioma; they could be used as independent prognostic factor for glioma.

  7. Curcumin promotes apoptosis in A549/DDP multidrug-resistant human lung adenocarcinoma cells through an miRNA signaling pathway

    SciTech Connect

    Zhang, Jian; Zhang, Tao; Ti, Xinyu; Shi, Jieran; Wu, Changgui; Ren, Xinling; Yin, Hong

    2010-08-13

    Research highlights: {yields} Curcumin had anti-cancer effects on A549/DDP multidrug-resistant human lung adenocarcinoma cells {yields} Curcumin promotes apoptosis in A549/DDP cells through a miRNA signaling pathway {yields} Curcumin induces A549/DDP cell apoptosis by downregulating miR-186* {yields} miR-186* may serve as a potential gene therapy target for refractory lung cancer that is sensitive to curcumin -- Abstract: Curcumin extracted from the rhizomes of Curcuma longa L. has been shown to have inhibitory effects on cancers through its anti-proliferative and pro-apoptotic activities. Emerging evidence demonstrates that curcumin can overcome drug resistance to classical chemotherapies. Thus, the mechanisms underlying the anti-tumor activities of curcumin require further study. In our study, we first demonstrated that curcumin had anti-cancer effects on A549/DDP multidrug-resistant human lung adenocarcinoma cells. Further studies showed that curcumin altered miRNA expression; in particular, significantly downregulated the expression of miR-186* in A549/DDP. In addition, transfection of cells with a miR-186* inhibitor promoted A549/DDP apoptosis, and overexpression of miR-186* significantly inhibited curcumin-induced apoptosis in A549/DDP cells. These observations suggest that miR-186* may serve as a potential gene therapy target for refractory lung cancer that is sensitive to curcumin.

  8. Morphine-treatment of human monocyte-derived macrophages induces differential miRNA and protein expression: Impact on inflammation and oxidative stress in the Central Nervous System

    PubMed Central

    Dave, Rajnish S.; Khalili, Kamel

    2010-01-01

    HIV-1-infected opiate abusers often exhibit an accelerated form of HIV-1 associated dementia and enhanced neurological dysfunction. Productive HIV-1 infection of microglia and perivascular macrophages and the resultant secretion of neurotoxic molecules by these cells contribute to this phenomenon. In order to understand the role of morphine in this process, we performed a genome-wide association study at the microRNA (miRNA) and protein levels in human monocyte-derived macrophages (h-mdms). A total of 26 differentially expressed miRNA were identified (p < 0.01), of which hsa-miR-15b and hsa-miR-181b had the greatest increase and decrease in expression levels, respectively. Computational analysis predicted fibroblast growth factor-2 (FGF-2) as the strongest target gene for hsa-miR15b. Of note, we observed a decrease in FGF-2 protein expression in response to morphine. Both hsa-miR-15b and hsa-miR-181b have several predicted gene targets involved in inflammation and T-cell activation pathways. In this context, we observed induction of MCP-2 and IL-6 by morphine. Moreover, proteomic analysis revealed the induction of mitochondrial superoxide dismutase in response to morphine treatment. HIV-1 infection did not induce mitochondrial superoxide dismutase. Collectively, these observations demonstrate that morphine induces inflammation and oxidative stress in h-mdms thereby contributing to expansion of HIV-1 CNS reservoir expansion and disease progression. Of note, differentially expressed miRNAs (hsa-miR-15b and 181-b) may have a potential role in regulating these processes. PMID:20564181

  9. Detection of Acute Radiation Sickness: A Feasibility Study in Non-Human Primates Circulating miRNAs for Triage in Radiological Events

    PubMed Central

    Menon, Naresh; Rogers, Claude J.; Lukaszewicz, Agnes I.; Axtelle, James; Yadav, Marshleen; Song, Feifei; Chakravarti, Arnab; Jacob, Naduparambil K.

    2016-01-01

    Development of biomarkers capable of estimating absorbed dose is critical for effective triage of affected individuals after radiological events. Levels of cell-free circulating miRNAs in plasma were compared for dose-response analysis in non-human primates (NHP) exposed to lethal (6.5 Gy) and sub-lethal (1 and 3 Gy) doses over a 7 day period. The doses and test time points were selected to mimic triage needs in the event of a mass casualty radiological event. Changes in miRNA abundance in irradiated animals were compared to a non-irradiated cohort and a cohort experiencing acute inflammation response from exposure to lipopolysaccharide (LPS). An amplification-free, hybridization-based direct digital counting method was used for evaluation of changes in microRNAs in plasma from all animals. Consistent with previous murine studies, circulating levels of miR-150-5p exhibited a dose- and time-dependent decrease in plasma. Furthermore, plasma miR-150-5p levels were found to correlate well with lymphocyte and neutrophil depletion kinetics. Additionally, plasma levels of several other evolutionarily and functionally conserved miRNAs were found altered as a function of dose and time. Interestingly, miR-574-5p exhibited a distinct, dose-dependent increase 24 h post irradiation in NHPs with lethal versus sub-lethal exposure before returning to the baseline level by day 3. This particular miRNA response was not detected in previous murine studies but was observed in animals exposed to LPS, indicating distinct molecular and inflammatory responses. Furthermore, an increase in low-abundant miR-126, miR-144, and miR-21 as well as high-abundant miR-1-3p and miR-206 was observed in irradiated animals on day 3 and/or day 7. The data from this study could be used to develop a multi-marker panel with known tissue-specific origin that could be used for developing rapid assays for dose assessment and evaluation of radiation injury on multiple organs. Furthermore this approach may be

  10. SeqBuster, a bioinformatic tool for the processing and analysis of small RNAs datasets, reveals ubiquitous miRNA modifications in human embryonic cells.

    PubMed

    Pantano, Lorena; Estivill, Xavier; Martí, Eulàlia

    2010-03-01

    High-throughput sequencing technologies enable direct approaches to catalog and analyze snapshots of the total small RNA content of living cells. Characterization of high-throughput sequencing data requires bioinformatic tools offering a wide perspective of the small RNA transcriptome. Here we present SeqBuster, a highly versatile and reliable web-based toolkit to process and analyze large-scale small RNA datasets. The high flexibility of this tool is illustrated by the multiple choices offered in the pre-analysis for mapping purposes and in the different analysis modules for data manipulation. To overcome the storage capacity limitations of the web-based tool, SeqBuster offers a stand-alone version that permits the annotation against any custom database. SeqBuster integrates multiple analyses modules in a unique platform and constitutes the first bioinformatic tool offering a deep characterization of miRNA variants (isomiRs). The application of SeqBuster to small-RNA datasets of human embryonic stem cells revealed that most miRNAs present different types of isomiRs, some of them being associated to stem cell differentiation. The exhaustive description of the isomiRs provided by SeqBuster could help to identify miRNA-variants that are relevant in physiological and pathological processes. SeqBuster is available at http://estivill_lab.crg.es/seqbuster.

  11. MiRNA profiling provides insights on adverse effects of Cr(VI) in the midgut tissues of Drosophila melanogaster.

    PubMed

    Chandra, Swati; Pandey, Ashutosh; Chowdhuri, Debapratim Kar

    2015-01-01

    Cr(VI), a well-known environmental chemical, is reported to cause various adverse effects on exposed organisms including genomic instability and carcinogenesis. Despite available information on the underlying mechanism of Cr(VI) induced toxicity, studies regarding toxicity modulation by epigenetic mechanisms are limited. It was therefore, hypothesized that the global miRNA profiling in Cr(VI) exposed Drosophila, a genetically tractable model organism, will provide information about mis-regulated miRNAs along with their targeted genes and relevant processes. Third instar larvae of Drosophila melanogaster (Oregon R(+)) were exposed to 5.0-20.0 μg/ml of Cr(VI) for 24 and 48 h. Following miRNA profile analysis on an Agilent platform, 28 of the 36 differentially expressed miRNAs were found to be significantly mis-regulated targeting major biological processes viz., DNA damage repair, oxidation-reduction processes, development and differentiation. Down-regulation of mus309 and mus312 under DNA repair, acon to oxidation-reduction and pyd to stress activated MAPK cascade respectively belonging to these gene ontology classes concurrent with up-regulation of dme-miR-314-3p, dme-miR-79-3p and dme-miR-12-5p confirm their functional involvement against Cr(VI) exposure. These findings assume significance since majority of the target genes in Drosophila have functional homologues in humans. The study further recommends Drosophila as a model to explore the role of miRNAs in xenobiotic induced toxicity.

  12. Perspectives on Agile Coaching

    NASA Astrophysics Data System (ADS)

    Fraser, Steven; Lundh, Erik; Davies, Rachel; Eckstein, Jutta; Larsen, Diana; Vilkki, Kati

    There are many perspectives to agile coaching including: growing coaching expertise, selecting the appropriate coach for your context; and eva luating value. A coach is often an itinerant who may observe, mentor, negotiate, influence, lead, and/or architect everything from team organization to system architecture. With roots in diverse fields ranging from technology to sociology coaches have differing motivations and experience bases. This panel will bring together coaches to debate and discuss various perspectives on agile coaching. Some of the questions to be addressed will include: What are the skills required for effective coaching? What should be the expectations for teams or individu als being coached? Should coaches be: a corporate resource (internal team of consultants working with multiple internal teams); an integral part of a specific team; or external contractors? How should coaches exercise influence and au thority? How should management assess the value of a coaching engagement? Do you have what it takes to be a coach? - This panel will bring together sea soned agile coaches to offer their experience and advice on how to be the best you can be!

  13. Response of MiRNA-22-3p and MiRNA-149-5p to Folate Deficiency and the Differential Regulation of MTHFR Expression in Normal and Cancerous Human Hepatocytes

    PubMed Central

    Li, Chao; Ni, Juan; Liu, Yao-Xian; Wang, Han; Liang, Zi-Qing; Wang, Xu

    2017-01-01

    Background/Aims Folic acid (FA) is a core micronutrient involved in DNA synthesis/methylation, and the metabolism of FA is responsible for genomic stability. MicroRNAs may affect gene expression during folate metabolism when cellular homeostasis is changed. This study aimed to reveal the relationship between FA deficiency and the expression of miR-22-p/miR-149-5p and the targeted regulation of miR-22-3p/miR-149-5p on the key folate metabolic gene Methylenetetrahydrofolate reductase (MTHFR). Methods Normal (HL-7702 cells) and cancerous (QGY-7703 cells) human hepatocytes were intervened in modified RPMI 1640 with FA deficiency for 21 days. The interaction between MTHFR and the tested miRNAs was verified by Dual-Luciferase Reporter Assays. The changes in the expression of miR-22-3p/miR-149-5p in response to FA deficiency were detected by Poly (A) Tailing RT-qPCR, and the expression of MTHFR at both the transcriptional and translational levels was determined by RT-qPCR and Western blotting, respectively. Result MiR-22-3p/miR-149-5p directly targeted the 3’UTR sequence of the MTHFR gene. FA deficiency led to an upregulation of miR-22-3p/miR-149-5p expression in QGY-7703/HL-7702 cells, while the transcription of MTHFR was decreased in QGY-7703 cells but elevated in HL-7702 cells. Western blotting showed that FA deficiency resulted in a decline of the MTHFR protein in QGY-7703 cells, whereas in HL-7702 cells, the MTHFR protein level remained constant. Conclusion The results suggested that miR-22-3p/miR-149-5p exert different post-transcriptional effects on MTHFR under conditions of FA deficiency in normal and cancerous human hepatocytes. The results also implied that miR-22-3p/miR-149-5p might exert anticancer effects in cases of long-term FA deficiency. PMID:28045918

  14. Operational Agility (La Maniabilite Operationnelle)

    DTIC Science & Technology

    1994-04-01

    describe how to go further and how to set up an analytical framework for the analysis of another fundamental property of modern combat aircraft, that is... analytical framework for the analysis of airframe agility and for the derivation of agility metrics. A general consensus has been found in relating agility...Gianchecchi, Aernmacchi Lt Col. G. Fristachi, Italian Air Force Prof. M. Innocenti, Auburn University/University of Pisa United Kingdom Mr P. Gordon

  15. Diet and lifestyle factors associated with miRNA expression in colorectal tissue

    PubMed Central

    Slattery, Martha L; Herrick, Jennifer S; Mullany, Lila E; Stevens, John R; Wolff, Roger K

    2017-01-01

    MicroRNAs (miRNAs) are small non-protein-coding RNA molecules that regulate gene expression. Diet and lifestyle factors have been hypothesized to be involved in the regulation of miRNA expression. In this study it was hypothesized that diet and lifestyle factors are associated with miRNA expression. Data from 1,447 cases of colorectal cancer to evaluate 34 diet and lifestyle variables using miRNA expression in normal colorectal mucosa as well as for differential expression between paired carcinoma and normal tissue were used. miRNA data were obtained using an Agilent platform. Multiple comparisons were adjusted for using the false discovery rate q-value. There were 250 miRNAs differentially expressed between carcinoma and normal colonic tissue by level of carbohydrate intake and 198 miRNAs differentially expressed by the level of sucrose intake. Of these miRNAs, 166 miRNAs were differentially expressed for both carbohydrate intake and sucrose intake. Ninety-nine miRNAs were differentially expressed by the level of whole grain intake in normal colonic mucosa. Level of oxidative balance score was associated with 137 differentially expressed miRNAs between carcinoma and paired normal rectal mucosa. Additionally, 135 miRNAs were differentially expressed in colon tissue based on recent NSAID use. Other dietary factors, body mass index, waist and hip circumference, and long-term physical activity levels did not alter miRNA expression after adjustment for multiple comparisons. These results suggest that diet and lifestyle factors regulate miRNA level. They provide additional support for the influence of carbohydrate, sucrose, whole grains, NSAIDs, and oxidative balance score on colorectal cancer risk. PMID:28053552

  16. miRNA-320a inhibits tumor proliferation and invasion by targeting c-Myc in human hepatocellular carcinoma

    PubMed Central

    Xie, Fei; Yuan, Yuncang; Xie, Luyang; Ran, Pengzhan; Xiang, Xudong; Huang, Qionglin; Qi, Guoxiang; Guo, Xiaopeng; Xiao, Chunjie; Zheng, Shangyong

    2017-01-01

    Background Downregulated expression levels of microRNA-320a (miR-320a) were found in primary breast cancers and colorectal cancer. Previous findings indicated that miRNA-320a may involve in the cancer development. In this study, we explored the roles of miR-320a by targeting c-Myc in the tumor growth of hepatocellular carcinoma (HCC). Methods Quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to detect the expression of miR-320a in 50 HCC tissues and four HCC cells. Luciferase reporter assay was conducted to confirm the direct downstream target of miR-320a in HEK-293 cells. The effect of miR-320a on endogenous c-Myc expression was investigated by transfecting miR-320a mimics into HepG2 and QGY-7703 cell lines. The c-Myc and miR-320a expressions were analyzed by immunohistochemistry (IHC) and qRT-PCR in the same HCC tissues. Furthermore, the biological functional correlation of miR-320a with c-Myc was determined by studying the effect of miR-320a mimics or c-Myc small interfering RNA (siRNA) on HCC cell proliferation and invasion. Results The expression of miR-320a was downregulated in 50 HCC tissues and 4 HCC cells. Luciferase assay revealed that c-Myc is a direct target of miR-320a. IHC and Western blot analysis showed that the c-Myc expression was inhibited by miR-320a in HCC tissues and cell lines. Upregulation of miR-320a suppressed the HCC cell proliferation and invasion capacity induced by inhibiting c-Myc, and the results were consistent with the effects of c-Myc siRNA on tumor suppression. These results revealed that miRNA-320a inhibits tumor proliferation and invasion by targeting c-Myc in HCC cells. Conclusion Our results showed that miR-320a functions as a tumor suppressor in HCC. By targeting c-Myc directly, miR-320a inhibits the HCC cell growth. Our studies provide evidence of miR-320a as a potentially target for HCC treatment. PMID:28243124

  17. Agile Walking Robot

    NASA Technical Reports Server (NTRS)

    Larimer, Stanley J.; Lisec, Thomas R.; Spiessbach, Andrew J.; Waldron, Kenneth J.

    1990-01-01

    Proposed agile walking robot operates over rocky, sandy, and sloping terrain. Offers stability and climbing ability superior to other conceptual mobile robots. Equipped with six articulated legs like those of insect, continually feels ground under leg before applying weight to it. If leg sensed unexpected object or failed to make contact with ground at expected point, seeks alternative position within radius of 20 cm. Failing that, robot halts, examines area around foot in detail with laser ranging imager, and replans entire cycle of steps for all legs before proceeding.

  18. Agile Infrastructure Monitoring

    NASA Astrophysics Data System (ADS)

    Andrade, P.; Ascenso, J.; Fedorko, I.; Fiorini, B.; Paladin, M.; Pigueiras, L.; Santos, M.

    2014-06-01

    At the present time, data centres are facing a massive rise in virtualisation and cloud computing. The Agile Infrastructure (AI) project is working to deliver new solutions to ease the management of CERN data centres. Part of the solution consists in a new "shared monitoring architecture" which collects and manages monitoring data from all data centre resources. In this article, we present the building blocks of this new monitoring architecture, the different open source technologies selected for each architecture layer, and how we are building a community around this common effort.

  19. Frequency agile optical parametric oscillator

    DOEpatents

    Velsko, Stephan P.

    1998-01-01

    The frequency agile OPO device converts a fixed wavelength pump laser beam to arbitrary wavelengths within a specified range with pulse to pulse agility, at a rate limited only by the repetition rate of the pump laser. Uses of this invention include Laser radar, LIDAR, active remote sensing of effluents/pollutants, environmental monitoring, antisensor lasers, and spectroscopy.

  20. Frequency agile optical parametric oscillator

    DOEpatents

    Velsko, S.P.

    1998-11-24

    The frequency agile OPO device converts a fixed wavelength pump laser beam to arbitrary wavelengths within a specified range with pulse to pulse agility, at a rate limited only by the repetition rate of the pump laser. Uses of this invention include Laser radar, LIDAR, active remote sensing of effluents/pollutants, environmental monitoring, antisensor lasers, and spectroscopy. 14 figs.

  1. miRNA Isolation from FFPET Specimen: A Technical Comparison of miRNA and Total RNA Isolation Methods.

    PubMed

    Nagy, Zsófia Brigitta; Wichmann, Barnabás; Kalmár, Alexandra; Barták, Barbara Kinga; Tulassay, Zsolt; Molnár, Béla

    2016-07-01

    MiRNA remain stable for detection and PCR-based amplification in FFPE tissue samples. Several miRNA extraction kits are available, however miRNA fraction, as part of total RNA can be isolated using total RNA purification methods, as well. Our primary aim was to compare four different miRNA and total RNA isolation methods from FFPE tissues. Further purposes were to evaluate quantitatively and qualitatively the yield of the isolated miRNA. MiRNAs were isolated from normal colorectal cancer FFPE specimens from the same patients. Two miRNA isolation kits (High Pure miRNA Isolation Kit, miRCURY™ RNA Isolation Kit) and two total RNA isolation kits were compared (High Pure RNA Paraffin Kit, MagNA Pure 96 Cellular RNA LV Kit). Quantity and quality were determined, expression analysis was performed by real-time PCR using qPCR Human Panel I + II (Exiqon) method detecting 742 human miRNAs in parallel. The yield of total RNA was found to be higher than miRNA purification protocols (in CRC: Ex: 0203 ± 0021 μg; HPm: 1,45 ± 0,8 μg; HPp: 21,36 ± 4,98 μg; MP: 8,6 ± 5,1 μg). MiRNAs were detected in lower relative quantity of total RNA compared to the miRNA kits. Higher number of miRNAs could be detected by the miRNA isolation kits in comparison to the total RNA isolation methods. (Ex: 497 ± 16; HPm: 542 ± 11; HPp: 332 ± 36; MP: 295 ± 74). Colon specific miRNAs (miR-21-5p;-34-5p) give satisfying results by miRNA isolation kits. Although miRNA can be detected also after total RNA isolation methods, for reliable and reproducible miRNA expression profiling the use of miRNA isolation kits are more suitable.

  2. Automation of DNA and miRNA co-extraction for miRNA-based identification of human body fluids and tissues.

    PubMed

    Kulstein, Galina; Marienfeld, Ralf; Miltner, Erich; Wiegand, Peter

    2016-10-01

    In the last years, microRNA (miRNA) analysis came into focus in the field of forensic genetics. Yet, no standardized and recommendable protocols for co-isolation of miRNA and DNA from forensic relevant samples have been developed so far. Hence, this study evaluated the performance of an automated Maxwell® 16 System-based strategy (Promega) for co-extraction of DNA and miRNA from forensically relevant (blood and saliva) samples compared to (semi-)manual extraction methods. Three procedures were compared on the basis of recovered quantity of DNA and miRNA (as determined by real-time PCR and Bioanalyzer), miRNA profiling (shown by Cq values and extraction efficiency), STR profiles, duration, contamination risk and handling. All in all, the results highlight that the automated co-extraction procedure yielded the highest miRNA and DNA amounts from saliva and blood samples compared to both (semi-)manual protocols. Also, for aged and genuine samples of forensically relevant traces the miRNA and DNA yields were sufficient for subsequent downstream analysis. Furthermore, the strategy allows miRNA extraction only in cases where it is relevant to obtain additional information about the sample type. Besides, this system enables flexible sample throughput and labor-saving sample processing with reduced risk of cross-contamination.

  3. Integrative analysis of genes and miRNA alterations in human embryonic stem cells-derived neural cells after exposure to silver nanoparticles.

    PubMed

    Oh, Jung-Hwa; Son, Mi-Young; Choi, Mi-Sun; Kim, Soojin; Choi, A-Young; Lee, Hyang-Ae; Kim, Ki-Suk; Kim, Janghwan; Song, Chang Woo; Yoon, Seokjoo

    2016-05-15

    Given the rapid growth of engineered and customer products made of silver nanoparticles (Ag NPs), understanding their biological and toxicological effects on humans is critically important. The molecular developmental neurotoxic effects associated with exposure to Ag NPs were analyzed at the physiological and molecular levels, using an alternative cell model: human embryonic stem cell (hESC)-derived neural stem/progenitor cells (NPCs). In this study, the cytotoxic effects of Ag NPs (10-200μg/ml) were examined in these hESC-derived NPCs, which have a capacity for neurogenesis in vitro, at 6 and 24h. The results showed that Ag NPs evoked significant toxicity in hESC-derived NPCs at 24h in a dose-dependent manner. In addition, Ag NPs induced cell cycle arrest and apoptosis following a significant increase in oxidative stress in these cells. To further clarify the molecular mechanisms of the toxicological effects of Ag NPs at the transcriptional and post-transcriptional levels, the global expression profiles of genes and miRNAs were analyzed in hESC-derived NPCs after Ag NP exposure. The results showed that Ag NPs induced oxidative stress and dysfunctional neurogenesis at the molecular level in hESC-derived NPCs. Based on this hESC-derived neural cell model, these findings have increased our understanding of the molecular events underlying developmental neurotoxicity induced by Ag NPs in humans.

  4. Differential expression of microRNA (miRNA) in chordoma reveals a role for miRNA-1 in Met expression.

    PubMed

    Duan, Zhenfeng; Choy, Edwin; Nielsen, G Petur; Rosenberg, Andrew; Iafrate, John; Yang, Cao; Schwab, Joe; Mankin, Henry; Xavier, Ramnik; Hornicek, Francis J

    2010-06-01

    Emerging evidence suggests that microRNA (miRNA) expression signatures in cancer may have important diagnostic, prognostic, and therapeutic value, but there is no data on miRNA expression in chordoma. The purpose of this study was to identify the role of miRNAs in human chordoma. We analyzed miRNA expression in chordoma-derived cell lines and chordoma tissue by using miRNA microarray technology with unsupervised hierarchical clustering analysis. The relative expression levels of these miRNAs were confirmed by real-time quantitative RT-PCR and Northern blot analysis. To characterize the potential role of miRNA-1, miRNA-1 was stably transfected into a chordoma cell line, UCH1. The expression of miRNA-1 targeted gene Met in chordoma tissues was also studied. We observe that human chordoma tissues and cell lines can be distinguished from normal muscle tissue by comparing miRNA expression profiles. Several miRNAs were differentially expressed in chordoma cell lines compared to controls, and similar expression patterns were found in primary chordoma tissues. Importantly, we were able to show for the first time, to our knowledge, that expression of miRNA-1 and miRNA-206, two miRNAs implicated in a number of other cancer types, were markedly decreased in both chordoma tissues and cell lines. When chordoma cell lines were transfected with miRNA-1, downregulation of known miRNA-1 targets was observed. These targets included Met and HDAC4-two genes that were observed to be overexpressed in chordoma. Our results demonstrate that some miRNAs are differentially expressed in chordoma and, in particular, miRNA-1 may have a functional effect on chordoma tumor pathogenesis.

  5. Role of miRNA in cancer diagnosis, prognosis, therapy and regulation of its expression by Epstein-Barr virus and human papillomaviruses: With special reference to oral cancer.

    PubMed

    Chawla, Jatinder Pal Singh; Iyer, Nageshwar; Soodan, Kanwaldeep Singh; Sharma, Atul; Khurana, Sunpreet Kaur; Priyadarshni, Pratiksha

    2015-08-01

    MicroRNAs (miRNAs) belong to class of small non-coding RNAs that regulate numerous biological processes by targeting broad set of messenger RNAs. Research on miRNA-based biomarkers has witnessed phenomenal growth, owing to non-invasive nature of miRNA based screening assays and their sensitivity and specificity in detecting cancers. Their discovery in humans in 2000 has led to an explosion in research in terms of their role as biomarker, therapeutic target and trying to elucidate their function. This review aims to summarize the function of microRNAs as well as to examine how dysregulation at any step in their biogenesis or functional pathway can play a role in development of cancer, together with its possible involvement in oral cancer. Overexpression of oncogenic miRNA may reduce protein products of tumor-suppressor genes but loss of tumor-suppressor miRNA expression may cause elevated levels of oncogenic protein. One or both of these alterations could represent new targets for cancer diagnosis and treatment in future. Many researchers have focused on genetic and epigenetic alterations in OSCC cells. The genetic susceptibility, endemic environment factors, and Epstein-Barr virus (EBV) infection are believed to be the major etiologic factors of OSCC. Once metastasis occurs, prognosis is very poor. It is urgently needed to develop biomarkers for early clinical diagnosis/prognosis, and novel effective therapies for oral carcinoma. High-risk HPV infection leads to aberrant expression of cellular oncogenic and tumor suppressive miRNAs. The emergence of miRNA knowledge, and its potential interactive action with such alterations, therefore creates new understanding of cell transformation.

  6. Agile manufacturing concept

    NASA Astrophysics Data System (ADS)

    Goldman, Steven L.

    1994-03-01

    The initial conceptualization of agile manufacturing was the result of a 1991 study -- chaired by Lehigh Professor Roger N. Nagel and California-based entrepreneur Rick Dove, President of Paradigm Shifts, International -- of what it would take for U.S. industry to regain global manufacturing competitiveness by the early twenty-first century. This industry-led study, reviewed by senior management at over 100 companies before its release, concluded that incremental improvement of the current system of manufacturing would not be enough to be competitive in today's global marketplace. Computer-based information and production technologies that were becoming available to industry opened up the possibility of an altogether new system of manufacturing, one that would be characterized by a distinctive integration of people and technologies; of management and labor; of customers, producers, suppliers, and society.

  7. Towards Agile Ontology Maintenance

    NASA Astrophysics Data System (ADS)

    Luczak-Rösch, Markus

    Ontologies are an appropriate means to represent knowledge on the Web. Research on ontology engineering reached practices for an integrative lifecycle support. However, a broader success of ontologies in Web-based information systems remains unreached while the more lightweight semantic approaches are rather successful. We assume, paired with the emerging trend of services and microservices on the Web, new dynamic scenarios gain momentum in which a shared knowledge base is made available to several dynamically changing services with disparate requirements. Our work envisions a step towards such a dynamic scenario in which an ontology adapts to the requirements of the accessing services and applications as well as the user's needs in an agile way and reduces the experts' involvement in ontology maintenance processes.

  8. Aircraft agility maneuvers

    NASA Technical Reports Server (NTRS)

    Cliff, Eugene M.; Thompson, Brian G.

    1992-01-01

    A new dynamic model for aircraft motions is presented. This model can be viewed as intermediate between a point-mass model, in which the body attitude angles are control-like, and a rigid-body model, in which the body-attitude angles evolve according to Newton's Laws. Specifically, consideration is given to the case of symmetric flight, and a model is constructed in which the body roll-rate and the body pitch-rate are the controls. In terms of this body-rate model a minimum-time heading change maneuver is formulated. When the bounds on the body-rates are large the results are similar to the point-mass model in that the model can very quickly change the applied forces and produce an acceleration to turn the vehicle. With finite bounds on these rates, the forces change in a smooth way. This leads to a measurable effect of agility.

  9. Elements of an Art - Agile Coaching

    NASA Astrophysics Data System (ADS)

    Lundh, Erik

    This tutorial gives you a lead on becoming or redefining yourself as an Agile Coach. Introduction to elements and dimensions of state-of-the-art Agile Coaching. How to position the agile coach to be effective in a larger setting. Making the agile transition - from a single team to thousands of people. How to support multiple teams as a coach. How to build a coaches network in your company. Challenges when the agile coach is a consultant and the organization is large.

  10. The Telemetry Agile Manufacturing Effort

    SciTech Connect

    Brown, K.D.

    1995-01-01

    The Telemetry Agile Manufacturing Effort (TAME) is an agile enterprising demonstration sponsored by the US Department of Energy (DOE). The project experimented with new approaches to product realization and assessed their impacts on performance, cost, flow time, and agility. The purpose of the project was to design the electrical and mechanical features of an integrated telemetry processor, establish the manufacturing processes, and produce an initial production lot of two to six units. This paper outlines the major methodologies utilized by the TAME, describes the accomplishments that can be attributed to each methodology, and finally, examines the lessons learned and explores the opportunities for improvement associated with the overall effort. The areas for improvement are discussed relative to an ideal vision of the future for agile enterprises. By the end of the experiment, the TAME reduced production flow time by approximately 50% and life cycle cost by more than 30%. Product performance was improved compared with conventional DOE production approaches.

  11. Agile manufacturing: The factory of the future

    NASA Technical Reports Server (NTRS)

    Loibl, Joseph M.; Bossieux, Terry A.

    1994-01-01

    The factory of the future will require an operating methodology which effectively utilizes all of the elements of product design, manufacturing and delivery. The process must respond rapidly to changes in product demand, product mix, design changes or changes in the raw materials. To achieve agility in a manufacturing operation, the design and development of the manufacturing processes must focus on customer satisfaction. Achieving greatest results requires that the manufacturing process be considered from product concept through sales. This provides the best opportunity to build a quality product for the customer at a reasonable rate. The primary elements of a manufacturing system include people, equipment, materials, methods and the environment. The most significant and most agile element in any process is the human resource. Only with a highly trained, knowledgeable work force can the proper methods be applied to efficiently process materials with machinery which is predictable, reliable and flexible. This paper discusses the affect of each element on the development of agile manufacturing systems.

  12. Inserting Agility in System Development

    DTIC Science & Technology

    2012-07-01

    Agile IT Acquisition, IT Box, Scrum Inserting Agility in System Development Matthew R. Kennedy and Lt Col Dan Ward, USAF With the fast-paced nature...1,700 individuals and 71 countries, found Scrum and eXtreme Programming to be the most widely followed method- ologies (VersionOne, 2007). Other...University http://www.dau.mil 259 Defense ARJ, July 2012, Vol. 19 No. 3 : 249–264 Scrum Scrum is a framework used for project management, which is

  13. Identification of candidate miRNA biomarkers from miRNA regulatory network with application to prostate cancer

    PubMed Central

    2014-01-01

    Background MicroRNAs (miRNAs) are a class of non-coding regulatory RNAs approximately 22 nucleotides in length that play a role in a wide range of biological processes. Abnormal miRNA function has been implicated in various human cancers including prostate cancer (PCa). Altered miRNA expression may serve as a biomarker for cancer diagnosis and treatment. However, limited data are available on the role of cancer-specific miRNAs. Integrative computational bioinformatics approaches are effective for the detection of potential outlier miRNAs in cancer. Methods The human miRNA-mRNA target network was reconstructed by integrating multiple miRNA-mRNA interaction datasets. Paired miRNA and mRNA expression profiling data in PCa versus benign prostate tissue samples were used as another source of information. These datasets were analyzed with an integrated bioinformatics framework to identify potential PCa miRNA signatures. In vitro q-PCR experiments and further systematic analysis were used to validate these prediction results. Results Using this bioinformatics framework, we identified 39 miRNAs as potential PCa miRNA signatures. Among these miRNAs, 20 had previously been identified as PCa aberrant miRNAs by low-throughput methods, and 16 were shown to be deregulated in other cancers. In vitro q-PCR experiments verified the accuracy of these predictions. miR-648 was identified as a novel candidate PCa miRNA biomarker. Further functional and pathway enrichment analysis confirmed the association of the identified miRNAs with PCa progression. Conclusions Our analysis revealed the scale-free features of the human miRNA-mRNA interaction network and showed the distinctive topological features of existing cancer miRNA biomarkers from previously published studies. A novel cancer miRNA biomarker prediction framework was designed based on these observations and applied to prostate cancer study. This method could be applied for miRNA biomarker prediction in other cancers. PMID

  14. Reprogramming of miRNA networks in cancer and leukemia.

    PubMed

    Volinia, Stefano; Galasso, Marco; Costinean, Stefan; Tagliavini, Luca; Gamberoni, Giacomo; Drusco, Alessandra; Marchesini, Jlenia; Mascellani, Nicoletta; Sana, Maria Elena; Abu Jarour, Ramzey; Desponts, Caroline; Teitell, Michael; Baffa, Raffaele; Aqeilan, Rami; Iorio, Marilena V; Taccioli, Cristian; Garzon, Ramiro; Di Leva, Gianpiero; Fabbri, Muller; Catozzi, Marco; Previati, Maurizio; Ambs, Stefan; Palumbo, Tiziana; Garofalo, Michela; Veronese, Angelo; Bottoni, Arianna; Gasparini, Pierluigi; Harris, Curtis C; Visone, Rosa; Pekarsky, Yuri; de la Chapelle, Albert; Bloomston, Mark; Dillhoff, Mary; Rassenti, Laura Z; Kipps, Thomas J; Huebner, Kay; Pichiorri, Flavia; Lenze, Dido; Cairo, Stefano; Buendia, Marie-Annick; Pineau, Pascal; Dejean, Anne; Zanesi, Nicola; Rossi, Simona; Calin, George A; Liu, Chang-Gong; Palatini, Jeff; Negrini, Massimo; Vecchione, Andrea; Rosenberg, Anne; Croce, Carlo M

    2010-05-01

    We studied miRNA profiles in 4419 human samples (3312 neoplastic, 1107 nonmalignant), corresponding to 50 normal tissues and 51 cancer types. The complexity of our database enabled us to perform a detailed analysis of microRNA (miRNA) activities. We inferred genetic networks from miRNA expression in normal tissues and cancer. We also built, for the first time, specialized miRNA networks for solid tumors and leukemias. Nonmalignant tissues and cancer networks displayed a change in hubs, the most connected miRNAs. hsa-miR-103/106 were downgraded in cancer, whereas hsa-miR-30 became most prominent. Cancer networks appeared as built from disjointed subnetworks, as opposed to normal tissues. A comparison of these nets allowed us to identify key miRNA cliques in cancer. We also investigated miRNA copy number alterations in 744 cancer samples, at a resolution of 150 kb. Members of miRNA families should be similarly deleted or amplified, since they repress the same cellular targets and are thus expected to have similar impacts on oncogenesis. We correctly identified hsa-miR-17/92 family as amplified and the hsa-miR-143/145 cluster as deleted. Other miRNAs, such as hsa-miR-30 and hsa-miR-204, were found to be physically altered at the DNA copy number level as well. By combining differential expression, genetic networks, and DNA copy number alterations, we confirmed, or discovered, miRNAs with comprehensive roles in cancer. Finally, we experimentally validated the miRNA network with acute lymphocytic leukemia originated in Mir155 transgenic mice. Most of miRNAs deregulated in these transgenic mice were located close to hsa-miR-155 in the cancer network.

  15. Reprogramming of miRNA networks in cancer and leukemia

    PubMed Central

    Volinia, Stefano; Galasso, Marco; Costinean, Stefan; Tagliavini, Luca; Gamberoni, Giacomo; Drusco, Alessandra; Marchesini, Jlenia; Mascellani, Nicoletta; Sana, Maria Elena; Abu Jarour, Ramzey; Desponts, Caroline; Teitell, Michael; Baffa, Raffaele; Aqeilan, Rami; Iorio, Marilena V.; Taccioli, Cristian; Garzon, Ramiro; Di Leva, Gianpiero; Fabbri, Muller; Catozzi, Marco; Previati, Maurizio; Ambs, Stefan; Palumbo, Tiziana; Garofalo, Michela; Veronese, Angelo; Bottoni, Arianna; Gasparini, Pierluigi; Harris, Curtis C.; Visone, Rosa; Pekarsky, Yuri; de la Chapelle, Albert; Bloomston, Mark; Dillhoff, Mary; Rassenti, Laura Z.; Kipps, Thomas J.; Huebner, Kay; Pichiorri, Flavia; Lenze, Dido; Cairo, Stefano; Buendia, Marie-Annick; Pineau, Pascal; Dejean, Anne; Zanesi, Nicola; Rossi, Simona; Calin, George A.; Liu, Chang-Gong; Palatini, Jeff; Negrini, Massimo; Vecchione, Andrea; Rosenberg, Anne; Croce, Carlo M.

    2010-01-01

    We studied miRNA profiles in 4419 human samples (3312 neoplastic, 1107 nonmalignant), corresponding to 50 normal tissues and 51 cancer types. The complexity of our database enabled us to perform a detailed analysis of microRNA (miRNA) activities. We inferred genetic networks from miRNA expression in normal tissues and cancer. We also built, for the first time, specialized miRNA networks for solid tumors and leukemias. Nonmalignant tissues and cancer networks displayed a change in hubs, the most connected miRNAs. hsa-miR-103/106 were downgraded in cancer, whereas hsa-miR-30 became most prominent. Cancer networks appeared as built from disjointed subnetworks, as opposed to normal tissues. A comparison of these nets allowed us to identify key miRNA cliques in cancer. We also investigated miRNA copy number alterations in 744 cancer samples, at a resolution of 150 kb. Members of miRNA families should be similarly deleted or amplified, since they repress the same cellular targets and are thus expected to have similar impacts on oncogenesis. We correctly identified hsa-miR-17/92 family as amplified and the hsa-miR-143/145 cluster as deleted. Other miRNAs, such as hsa-miR-30 and hsa-miR-204, were found to be physically altered at the DNA copy number level as well. By combining differential expression, genetic networks, and DNA copy number alterations, we confirmed, or discovered, miRNAs with comprehensive roles in cancer. Finally, we experimentally validated the miRNA network with acute lymphocytic leukemia originated in Mir155 transgenic mice. Most of miRNAs deregulated in these transgenic mice were located close to hsa-miR-155 in the cancer network. PMID:20439436

  16. Comprehensive Small RNA-Seq of Adeno-Associated Virus (AAV)-Infected Human Cells Detects Patterns of Novel, Non-Coding AAV RNAs in the Absence of Cellular miRNA Regulation

    PubMed Central

    Stutika, Catrin; Mietzsch, Mario; Gogol-Döring, Andreas; Weger, Stefan; Sohn, Madlen; Chen, Wei; Heilbronn, Regine

    2016-01-01

    Most DNA viruses express small regulatory RNAs, which interfere with viral or cellular gene expression. For adeno-associated virus (AAV), a small ssDNA virus with a complex biphasic life cycle miRNAs or other small regulatory RNAs have not yet been described. This is the first comprehensive Illumina-based RNA-Seq analysis of small RNAs expressed by AAV alone or upon co-infection with helper adenovirus or HSV. Several hotspots of AAV-specific small RNAs were detected mostly close to or within the AAV-ITR and apparently transcribed from the newly identified anti-p5 promoter. An additional small RNA hotspot was located downstream of the p40 promoter, from where transcription of non-coding RNAs associated with the inhibition of adenovirus replication were recently described. Parallel detection of known Ad and HSV miRNAs indirectly validated the newly identified small AAV RNA species. The predominant small RNAs were analyzed on Northern blots and by human argonaute protein-mediated co-immunoprecipitation. None of the small AAV RNAs showed characteristics of bona fide miRNAs, but characteristics of alternative RNA processing indicative of differentially regulated AAV promoter-associated small RNAs. Furthermore, the AAV-induced regulation of cellular miRNA levels was analyzed at different time points post infection. In contrast to other virus groups AAV infection had virtually no effect on the expression of cellular miRNA, which underscores the long-established concept that wild-type AAV infection is apathogenic. PMID:27611072

  17. Comprehensive Small RNA-Seq of Adeno-Associated Virus (AAV)-Infected Human Cells Detects Patterns of Novel, Non-Coding AAV RNAs in the Absence of Cellular miRNA Regulation.

    PubMed

    Stutika, Catrin; Mietzsch, Mario; Gogol-Döring, Andreas; Weger, Stefan; Sohn, Madlen; Chen, Wei; Heilbronn, Regine

    2016-01-01

    Most DNA viruses express small regulatory RNAs, which interfere with viral or cellular gene expression. For adeno-associated virus (AAV), a small ssDNA virus with a complex biphasic life cycle miRNAs or other small regulatory RNAs have not yet been described. This is the first comprehensive Illumina-based RNA-Seq analysis of small RNAs expressed by AAV alone or upon co-infection with helper adenovirus or HSV. Several hotspots of AAV-specific small RNAs were detected mostly close to or within the AAV-ITR and apparently transcribed from the newly identified anti-p5 promoter. An additional small RNA hotspot was located downstream of the p40 promoter, from where transcription of non-coding RNAs associated with the inhibition of adenovirus replication were recently described. Parallel detection of known Ad and HSV miRNAs indirectly validated the newly identified small AAV RNA species. The predominant small RNAs were analyzed on Northern blots and by human argonaute protein-mediated co-immunoprecipitation. None of the small AAV RNAs showed characteristics of bona fide miRNAs, but characteristics of alternative RNA processing indicative of differentially regulated AAV promoter-associated small RNAs. Furthermore, the AAV-induced regulation of cellular miRNA levels was analyzed at different time points post infection. In contrast to other virus groups AAV infection had virtually no effect on the expression of cellular miRNA, which underscores the long-established concept that wild-type AAV infection is apathogenic.

  18. Agile automated vision

    NASA Astrophysics Data System (ADS)

    Fandrich, Juergen; Schmitt, Lorenz A.

    1994-11-01

    The microelectronic industry is a protagonist in driving automated vision to new paradigms. Today semiconductor manufacturers use vision systems quite frequently in their fabs in the front-end process. In fact, the process depends on reliable image processing systems. In the back-end process, where ICs are assembled and packaged, today vision systems are only partly used. But in the next years automated vision will become compulsory for the back-end process as well. Vision will be fully integrated into every IC package production machine to increase yields and reduce costs. Modem high-speed material processing requires dedicated and efficient concepts in image processing. But the integration of various equipment in a production plant leads to unifying handling of data flow and interfaces. Only agile vision systems can act with these contradictions: fast, reliable, adaptable, scalable and comprehensive. A powerful hardware platform is a unneglectable requirement for the use of advanced and reliable, but unfortunately computing intensive image processing algorithms. The massively parallel SIMD hardware product LANTERN/VME supplies a powerful platform for existing and new functionality. LANTERN/VME is used with a new optical sensor for IC package lead inspection. This is done in 3D, including horizontal and coplanarity inspection. The appropriate software is designed for lead inspection, alignment and control tasks in IC package production and handling equipment, like Trim&Form, Tape&Reel and Pick&Place machines.

  19. RNASET2 silencing affects miRNAs and target gene expression pattern in a human ovarian cancer cell model.

    PubMed

    Turconi, Giovanna; Scaldaferri, Debora; Fabbri, Marco; Monti, Laura; Lualdi, Marta; Pedrini, Edoardo; Gribaldo, Laura; Taramelli, Roberto; Acquati, Francesco

    2016-12-01

    Ribonucleases (RNases) are hydrolytic enzymes endowed with the ability to either process or degrade ribonucleic acids. Among the many biological functions assigned to RNases, a growing attention has been recently devoted to the control of cancer growth, in the attempt to bring novel therapeutic approaches to clinical oncology. Indeed, several enzymes belonging to different ribonuclease families have been reported in the last decade to display a marked oncosuppressive activity in a wide range of experimental models. The human RNASET2 gene, the only member of the highly conserved T2/Rh/S family of endoribonucleolytic enzymes described in our species, has been shown to display oncosuppressive roles in both in vitro and in vivo models representing several human malignancies. In the present study, we extend previous findings obtained in ovarian cancer models to shed further light on the cell-autonomous roles played by this gene in the context of its oncosuppresive role and to show that RNASET2 silencing can significantly affect the transcriptional output in one of the most thoroughly investigated human ovarian cancer cell lines. Moreover, we report for the first time that RNASET2-mediated changes in the cell transcriptome are in part mediated by its apparent ability to affect the cell's microRNA expression pattern.

  20. Comprehensive expression analysis of miRNA in breast cancer at the miRNA and isomiR levels.

    PubMed

    Wu, Xianjin; Zeng, Rong; Wu, Shaoke; Zhong, Jixin; Yang, Lawei; Xu, Junfa

    2015-02-25

    Breast cancer (BC) is the main factor that leads cause of cancer death in women worldwide. A class of small non-coding RNAs, microRNAs (miRNAs), has been widely studied in human cancers as crucial regulatory molecule. Recent studies indicate that a series of isomiRs can be yielded from a miRNA locus, and these physiological miRNA isoforms have versatile roles in miRNA biogenesis. Herein, we performed a comprehensive analysis of miRNAs at the miRNA and isomiR levels in BC using next-generation sequencing data from The Cancer Genome Atlas (TCGA). Abnormally expressed miRNA (miR-21, miR-221, miR-155, miR-30e and miR-25) and isomiR profiles could be obtained at the miRNA and isomiR levels, and similar biological roles could be detected. IsomiR expression profiles should be further concerned, and especially isomiRs are actual regulatory molecules in the miRNA-mRNA regulatory networks. The study provides a comprehensive expression analysis at the miRNA and isomiR levels in BC, which indicates biological roles of isomiRs.

  1. What Does an Agile Coach Do?

    NASA Astrophysics Data System (ADS)

    Davies, Rachel; Pullicino, James

    The surge in Agile adoption has created a demand for project managers rather than direct their teams. A sign of this trend is the ever-increasing number of people getting certified as scrum masters and agile leaders. Training courses that introduce agile practices are easy to find. But making the transition to coach is not as simple as understanding what agile practices are. Your challenge as an Agile Coach is to support your team in learning how to wield their new Agile tools in creating great software.

  2. Comparative MiRNA Expressional Profiles and Molecular Networks in Human Small Bowel Tissues of Necrotizing Enterocolitis and Spontaneous Intestinal Perforation

    PubMed Central

    Tam, Yuk Him; Ma, Terence Ping Yuen; Lam, Hugh Simon; Cheung, Hon Ming; Lee, Kim Hung; To, Ka Fai; Li, Karen

    2015-01-01

    Background Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are acute intestinal conditions which could result in mortality and severe morbidity in preterm infants. Our objective was to identify dysregulated micro-RNAs (miRNAs) in small bowel tissues of NEC and SIP, and their possible roles in disease pathophysiology. Methods We performed differential miRNA arrays on tissues of NEC (n = 4), SIP (n = 4) and surgical-control (Surg-CTL; n = 4), and validated target miRNAs by qPCR (n = 10 each group). The association of target miRNAs with 52 dysregulated mRNAs was investigated by bioinformatics on functional and base-pair sequence algorithms, and correlation in same tissue samples. Results We presented the first miRNA profiles of NEC, SIP and Surg-CTL intestinal tissues in preterm infants. Of 28 validated miRNAs, 21 were significantly different between NEC or SIP and Surg-CTL. Limited overlapping in the aberrant expression of miRNAs between NEC and SIP indicated their distinct molecular mechanisms. A proposed network of dysregulated miRNA/mRNA pairs in NEC suggested interaction at bacterial receptor TLR4 (miR-31, miR-451, miR-203, miR-4793-3p), mediated via key transcription factors NFKB2 (miR-203), AP-1/FOSL1 (miR-194-3p), FOXA1 (miR-21-3p, miR-431 and miR-1290) and HIF1A (miR-31), and extended downstream to pathways of angiogenesis, arginine metabolism, cell adhesion and chemotaxis, extracellular matrix remodeling, hypoxia/oxidative stress, inflammation and muscle contraction. In contrast, upregulation of miR-451 and miR-223 in SIP suggested modulation of G-protein-mediated muscle contraction. Conclusions The robust response of miRNA dysregulation in NEC and SIP, and concerted involvement of specific miRNAs in the molecular networks indicated their crucial roles in mucosa integrity and disease pathophysiology. PMID:26274503

  3. Neuronal developmental gene and miRNA signatures induced by histone deacetylase inhibitors in human embryonic stem cells

    PubMed Central

    Meganathan, K; Jagtap, S; Srinivasan, S P; Wagh, V; Hescheler, J; Hengstler, J; Leist, M; Sachinidis, A

    2015-01-01

    Human embryonic stem cells (hESCs) may be applied to develop human-relevant sensitive in vitro test systems for monitoring developmental toxicants. The aim of this study was to identify potential developmental toxicity mechanisms of the histone deacetylase inhibitors (HDAC) valproic acid (VPA), suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) relevant to the in vivo condition using a hESC model in combination with specific differentiation protocols and genome-wide gene expression and microRNA profiling. Analysis of the gene expression data showed that VPA repressed neural tube and dorsal forebrain (OTX2, ISL1, EMX2 and SOX10)-related transcripts. In addition, VPA upregulates axonogenesis and ventral forebrain-associated genes, such as SLIT1, SEMA3A, DLX2/4 and GAD2. HDACi-induced expression of miR-378 and knockdown of miR-378 increases the expression of OTX2 and EMX2, which supports our hypothesis that HDACi targets forebrain markers through miR-378. In conclusion, multilineage differentiation in vitro test system is very sensitive for monitoring molecular activities relevant to in vivo neuronal developmental toxicity. Moreover, miR-378 seems to repress the expression of the OTX2 and EMX2 and therefore could be a regulator of the development of neural tube and dorsal forebrain neurons. PMID:25950486

  4. Small RNA zippers lock miRNA molecules and block miRNA function in mammalian cells

    PubMed Central

    Meng, Lingyu; Liu, Cuicui; Lü, Jinhui; Zhao, Qian; Deng, Shengqiong; Wang, Guangxue; Qiao, Jing; Zhang, Chuyi; Zhen, Lixiao; Lu, Ying; Li, Wenshu; Zhang, Yuzhen; Pestell, Richard G.; Fan, Huiming; Chen, Yi-Han; Liu, Zhongmin; Yu, Zuoren

    2017-01-01

    MicroRNAs (miRNAs) loss-of-function phenotypes are mainly induced by chemically modified antisense oligonucleotides. Here we develop an alternative inhibitor for miRNAs, termed ‘small RNA zipper'. It is designed to connect miRNA molecules end to end, forming a DNA–RNA duplex through a complementary interaction with high affinity, high specificity and high stability. Two miRNAs, miR-221 and miR-17, are tested in human breast cancer cell lines, demonstrating the 70∼90% knockdown of miRNA levels by 30–50 nM small RNA zippers. The miR-221 zipper shows capability in rescuing the expression of target genes of miR-221 and reversing the oncogenic function of miR-221 in breast cancer cells. In addition, we demonstrate that the miR-221 zipper attenuates doxorubicin resistance with higher efficiency than anti-miR-221 in human breast cancer cells. Taken together, small RNA zippers are a miRNA inhibitor, which can be used to induce miRNA loss-of-function phenotypes and validate miRNA target genes. PMID:28045030

  5. Circulating miRNAs is a potential marker for gefitinib sensitivity and correlation with EGFR mutational status in human lung cancers

    PubMed Central

    Zhao, Qiang; Cao, Jun; Wu, Yi-Chen; Liu, Xiang; Han, Jing; Huang, Xian-Cong; Jiang, Lie-Hao; Hou, Xiu-Xiu; Mao, Wei-Min; Ling, Zhi-Qiang

    2015-01-01

    miRNA expression is deregulated in non-small cell lung cancer (NSCLC), and some miRNAs are associated with gefitinib sensitivity. Here, we investigated if circulating miRNAs could be a useful biomarker for the prediction of EGFR mutation and the patient’s prognosis. The differential miRNAs related to gefitinib sensitivity were screened and identified by microRNA array. Using Taqman-based real-time RT-PCR, we analyzed the expression of selected miRNAs in tumor tissues and plasma of 150 NSCLC patients. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to determine the association between miRNAs expression and survival. Receiver operating characteristic curve analysis was also performed. Compared with PC9 cell line, 41 microRNAs detected by microarray were significantly differentially expressed in A549 and H1299 cells. The 5 selected hsa-miRNAs were all found differently expressed between wild and mutant EGFR carriers (all P<0.01). Down-regulation of 5 selected miRNAs were independently associated with lymphatic invasion (all P<0.01) and clinical stage (all P<0.01), respectively. Both down-regulation of has-miR-195 (P=0.012) and has-miR-21 (P=0.004) were associated with poor differentiation. All up-regulation of 5 has-miRNAs were associated with smoking (All P<0.05). 5 hsa-miRNAs were up-regulated both in plasma and tissue samples. A model including 4 hsa-miRNAs may predict EGFR mutational status and gefitinib-sensitivity (both AUC: 0.869). Plasma levels of has-miR-125b expression were associated with disease-free survival (P=0.033) and overall survival in the patients (P=0.028). In a word, Circulating 5 selected miRNAs may especially be useful in predicting EGFR mutation, and circulating hsa-miR-125b may have prognostic values in NSCLC patients. PMID:26175938

  6. Biorobotics: using robots to emulate and investigate agile locomotion.

    PubMed

    Ijspeert, Auke J

    2014-10-10

    The graceful and agile movements of animals are difficult to analyze and emulate because locomotion is the result of a complex interplay of many components: the central and peripheral nervous systems, the musculoskeletal system, and the environment. The goals of biorobotics are to take inspiration from biological principles to design robots that match the agility of animals, and to use robots as scientific tools to investigate animal adaptive behavior. Used as physical models, biorobots contribute to hypothesis testing in fields such as hydrodynamics, biomechanics, neuroscience, and prosthetics. Their use may contribute to the design of prosthetic devices that more closely take human locomotion principles into account.

  7. Genomic analysis of miRNAs in an extreme mammalian hibernator, the Arctic ground squirrel.

    PubMed

    Liu, Yuting; Hu, Wenchao; Wang, Haifang; Lu, Minghua; Shao, Chunxuan; Menzel, Corinna; Yan, Zheng; Li, Ying; Zhao, Sen; Khaitovich, Philipp; Liu, Mofang; Chen, Wei; Barnes, Brian M; Yan, Jun

    2010-09-01

    MicroRNAs (miRNAs) are 19- to 25-nucleotide-long small and noncoding RNAs now well-known for their regulatory roles in gene expression through posttranscriptional and translational controls. Mammalian hibernation is a physiological process involving profound changes in set-points for food consumption, body mass and growth, body temperature, and metabolic rate in which miRNAs may play important regulatory roles. In an initial study, we analyzed miRNAs in the liver of an extreme hibernating species, the Arctic ground squirrel (Spermophilus parryii), using massively parallel Illumina sequencing technology. We identified >200 ground squirrel miRNAs, including 18 novel miRNAs specific to ground squirrel and mir-506 that is fast evolving in the ground squirrel lineage. Comparing animals sampled after at least 8 days of continuous torpor (late torpid), within 5 h of a spontaneous arousal episode (early aroused), and 1-2 mo after hibernation had ended (nonhibernating), we identified differentially expressed miRNAs during hibernation, which are also compared with the results from two other miRNA profiling methods: Agilent miRNA microarray and real-time PCR. Among the most significant miRNAs, miR-320 and miR-378 were significantly underexpressed during both stages of hibernation compared with nonhibernating animals, whereas miR-486 and miR-451 were overexpressed in late torpor but returned in early arousal to the levels similar to those in nonhibernating animals. Analyses of their putative target genes suggest that these miRNAs could play an important role in suppressing tumor progression and cell growth during hibernation. High-throughput sequencing data and microarray data have been submitted to GEO database with accession: GSE19808.

  8. [Web server for prediction of miRNAs and their precursors and binding sites].

    PubMed

    Vorozheykin, P S; Titov, I I

    2015-01-01

    A microRNA (miRNA) is a small noncoding RNA molecule about 22 nucleotides in length. The paper describes a web server for predicting miRNAs and their precursors and binding sites. The predictions are based on either sequence similarity to known miRNAs of 223 organisms or context-structural hidden Markov models. It has been shown that the proposed methods of prediction of human miRNAs and pre-miRNAs outperform the existing ones in accuracy. The average deviation of predicted 5'-ends of human miRNAs from actual positions is 3.13 nt in the case of predicting one pair of complementary miRNAs (miRNA-miRNA* duplex). A useful option for our application is the prediction of an additional miRNA pair. In this mode, the pairs closest to actual miRNA deviate by 1.61 nt on average. The proposed method also shows good performance in predicting mouse miRNAs. Binding sites for miRNAs are predicted by two known approaches based on complementarity and thermodynamic stability of the miRNA-mRNA duplex and on a new approach, which takes into account miRNAs competition for the site. The role of the secondary structure in miRNA processing is considered. The web server is available at http://wwwmgs.bionet.nsc.ru/mgs/programs/rnaanalys/.

  9. Transcriptome profiling of microRNA by next-gen deep sequencing reveals known and novel miRNA species in the lipid fraction of human breast milk

    Technology Transfer Automated Retrieval System (TEKTRAN)

    While breast milk has unique health advantages for infants, the mechanisms by which it regulates the physiology of newborns are incompletely understood. miRNAs have been described as functioning transcellularly, and have been previously isolated in cell-free and exosomal form from bodily liquids (se...

  10. Agile Development of Advanced Prototypes

    DTIC Science & Technology

    2014-11-01

    genetically modified babies. A case where researchers supplemented women’s defective mitochondria with healthy mitochondria from a donor was...and immersive experience showing genetic engineering’s implication for the future of medicine. 15. SUBJECT TERMS Agile Development, Games for...provoking perspective on genetic engineering’s implication for the future of medicine. Experiencing Living with Prostheses (Xense) During this period

  11. Making Agile Work for You

    DTIC Science & Technology

    2011-07-20

    Extreme Programming (XP) • SCRUM • Dynamic Systems Development Method (DSDM) • Adaptive Software Development • Crystal • Feature-Driven Development...Carnegie Mellon University Twitter #seiwebinar SCRUM Scrum is an iterative, incremental methodology for managing agile software projects. The Team

  12. Differential expression of miRNA between the monolayer and three dimensional cells after ionizing radiation

    NASA Astrophysics Data System (ADS)

    Pan, Dong; Ren, Zhenxin; Hu, Burong

    2014-04-01

    We detect the expression of miRNA in 2D and 3D human lung epithelial cells (3KT). And our primary experimental results showed that more miRNA in 3D 3KT down regulated than in 2D 3KT cells after not only X-ray but also C-beam irradiation using the miRNA chip assay. Meanwhile, X-ray induced more significantly differential expression of miRNA when the relative expression value of miRNA in 3D cells were compared to 2D cells after irradiation.

  13. Crosstalk between kinases, phosphatases and miRNAs in cancer.

    PubMed

    Abrantes, Júlia L F; Tornatore, Thaís F; Pelizzaro-Rocha, Karin J; de Jesus, Marcelo B; Cartaxo, Rodrigo T; Milani, Renato; Ferreira-Halder, Carmen V

    2014-12-01

    Reversible phosphorylation of proteins, performed by kinases and phosphatases, is the major post translational protein modification in eukaryotic cells. This intracellular event represents a critical regulatory mechanism of several signaling pathways and can be related to a vast array of diseases, including cancer. Cancer research has produced increasing evidence that kinase and phosphatase activity can be compromised by mutations and also by miRNA silencing, performed by small non-coding and endogenously produced RNA molecules that lead to translational repression. miRNAs are believed to target about one-third of human mRNAs while a single miRNA may target about 200 transcripts simultaneously. Regulation of the phosphorylation balance by miRNAs has been a topic of intense research over the last years, spanning topics going as far as cancer aggressiveness and chemotherapy resistance. By addressing recent studies that have shown miRNA expression patterns as phenotypic signatures of cancers and how miRNA influence cellular processes such as apoptosis, cell cycle control, angiogenesis, inflammation and DNA repair, we discuss how kinases, phosphatases and miRNAs cooperatively act in cancer biology.

  14. The potential of miRNAs for diagnosis, treatment and monitoring of breast cancer.

    PubMed

    Bertoli, Gloria; Cava, Claudia; Castiglioni, Isabella

    2016-01-01

    Dysregulation of microRNAs (miRNAs) has a fundamental role in the initiation, development and progression of several human cancers, including breast cancer (BC), since strong evidence has shown that miRNAs can regulate the expression of oncogenes or tumor suppressor genes. A possible role of miRNAs in the diagnosis in BC has been demonstrated. As miRNAs has been found stable in biofluids, extracellular multiple miRNA profiles have been proposed as diagnostic tools, showing better diagnostic performance than individual miRNAs in BC. In this paper, based on the current literature, we present the role of microRNAs in the diagnosis and therapy monitoring of BC. Furthermore, we report new miRNA-based drugs that could be turned into promising therapy for BC, alone or in combination with conventional therapy. We also discuss how extracellular miRNAs could become new, easily accessible, affordable, non-invasive tools for BC patients.

  15. Urinary Exosomal miRNA Signature in Type II Diabetic Nephropathy Patients

    PubMed Central

    Delić, Denis; Eisele, Claudia; Schmid, Ramona; Baum, Patrick; Wiech, Franziska; Gerl, Martin; Zimdahl, Heike; Pullen, Steven S.; Urquhart, Richard

    2016-01-01

    MicroRNAs (miRNAs) are short non-coding RNA species which are important post-transcriptional regulators of gene expression and play an important role in the pathogenesis of diabetic nephropathy. miRNAs are present in urine in a remarkably stable form packaged in extracellular vesicles, predominantly exosomes. In the present study, urinary exosomal miRNA profiling was conducted in urinary exosomes obtained from 8 healthy controls (C), 8 patients with type II diabetes (T2D) and 8 patients with type II diabetic nephropathy (DN) using Agilent´s miRNA microarrays. In total, the expression of 16 miRNA species was deregulated (>2-fold) in DN patients compared to healthy donors and T2D patients: the expression of 14 miRNAs (miR-320c, miR-6068, miR-1234-5p, miR-6133, miR-4270, miR-4739, miR-371b-5p, miR-638, miR-572, miR-1227-5p, miR-6126, miR-1915-5p, miR-4778-5p and miR-2861) was up-regulated whereas the expression of 2 miRNAs (miR-30d-5p and miR-30e-5p) was down-regulated. Most of the deregulated miRNAs are involved in progression of renal diseases. Deregulation of urinary exosomal miRNAs occurred in micro-albuminuric DN patients but not in normo-albuminuric DN patients. We used qRT-PCR based analysis of the most strongly up-regulated miRNAs in urinary exosomes from DN patients, miRNAs miR-320c and miR-6068. The correlation of miRNA expression and micro-albuminuria levels could be replicated in a confirmation cohort. In conclusion, urinary exosomal miRNA content is altered in type II diabetic patients with DN. Deregulated miR-320c, which might have an impact on the TGF-β-signaling pathway via targeting thrombospondin 1 (TSP-1) shows promise as a novel candidate marker for disease progression in type II DN that should be evaluated in future studies. PMID:26930277

  16. An Investigation of Agility Issues in Scrum Teams Using Agility Indicators

    NASA Astrophysics Data System (ADS)

    Pikkarainen, Minna; Wang, Xiaofeng

    Agile software development methods have emerged and become increasingly popular in recent years; yet the issues encountered by software development teams that strive to achieve agility using agile methods are yet to be explored systematically. Built upon a previous study that has established a set of indicators of agility, this study investigates what issues are manifested in software development teams using agile methods. It is focussed on Scrum teams particularly. In other words, the goal of the chapter is to evaluate Scrum teams using agility indicators and therefore to further validate previously presented agility indicators within the additional cases. A multiple case study research method is employed. The findings of the study reveal that the teams using Scrum do not necessarily achieve agility in terms of team autonomy, sharing, stability and embraced uncertainty. The possible reasons include previous organizational plan-driven culture, resistance towards the Scrum roles and changing resources.

  17. Barriers to Achieving Mentally Agile Junior Leaders

    DTIC Science & Technology

    2009-01-21

    To help answer this question, this paper will describe the operational environment the agile leader must be prepared to operate within and the...senior leadership identified their need over eight years ago? To help answer this question, this paper will describe the operational environment the agile...to the reader. BARRIERS TO ACHIEVING MENTALLY AGILE JUNIOR LEADERS Persistent conflict and change characterize the strategic environment . We have

  18. Towards a Comparative Measure of Legged Agility

    DTIC Science & Technology

    2014-06-01

    so for this paper we explore the implications of a well-cited definition within the sports science community holding that agility is “a rapid whole...systems will have negligible agility according to our metric in accor- dance with biological observations that these motions require significantly less...W. Young, “Agility literature review: Classifications, training and testing,” Journal of sports sciences, vol. 24, no. 9, pp. 919–932, 2006. 19. D. L

  19. On the Biomimetic Design of Agile-Robot Legs

    PubMed Central

    Garcia, Elena; Arevalo, Juan Carlos; Muñoz, Gustavo; Gonzalez-de-Santos, Pablo

    2011-01-01

    The development of functional legged robots has encountered its limits in human-made actuation technology. This paper describes research on the biomimetic design of legs for agile quadrupeds. A biomimetic leg concept that extracts key principles from horse legs which are responsible for the agile and powerful locomotion of these animals is presented. The proposed biomimetic leg model defines the effective leg length, leg kinematics, limb mass distribution, actuator power, and elastic energy recovery as determinants of agile locomotion, and values for these five key elements are given. The transfer of the extracted principles to technological instantiations is analyzed in detail, considering the availability of current materials, structures and actuators. A real leg prototype has been developed following the biomimetic leg concept proposed. The actuation system is based on the hybrid use of series elasticity and magneto-rheological dampers which provides variable compliance for natural motion. From the experimental evaluation of this prototype, conclusions on the current technological barriers to achieve real functional legged robots to walk dynamically in agile locomotion are presented. PMID:22247667

  20. On the biomimetic design of agile-robot legs.

    PubMed

    Garcia, Elena; Arevalo, Juan Carlos; Muñoz, Gustavo; Gonzalez-de-Santos, Pablo

    2011-01-01

    The development of functional legged robots has encountered its limits in human-made actuation technology. This paper describes research on the biomimetic design of legs for agile quadrupeds. A biomimetic leg concept that extracts key principles from horse legs which are responsible for the agile and powerful locomotion of these animals is presented. The proposed biomimetic leg model defines the effective leg length, leg kinematics, limb mass distribution, actuator power, and elastic energy recovery as determinants of agile locomotion, and values for these five key elements are given. The transfer of the extracted principles to technological instantiations is analyzed in detail, considering the availability of current materials, structures and actuators. A real leg prototype has been developed following the biomimetic leg concept proposed. The actuation system is based on the hybrid use of series elasticity and magneto-rheological dampers which provides variable compliance for natural motion. From the experimental evaluation of this prototype, conclusions on the current technological barriers to achieve real functional legged robots to walk dynamically in agile locomotion are presented.

  1. Identification of Dirofilaria immitis miRNA using illumina deep sequencing

    PubMed Central

    2013-01-01

    The heartworm Dirofilaria immitis is the causative agent of cardiopulmonary dirofilariosis in dogs and cats, which also infects a wide range of wild mammals and humans. The complex life cycle of D. immitis with several developmental stages in its invertebrate mosquito vectors and its vertebrate hosts indicates the importance of miRNA in growth and development, and their ability to regulate infection of mammalian hosts. This study identified the miRNA profiles of D. immitis of zoonotic significance by deep sequencing. A total of 1063 conserved miRNA candidates, including 68 anti-sense miRNA (miRNA*) sequences, were predicted by computational methods and could be grouped into 808 miRNA families. A significant bias towards family members, family abundance and sequence nucleotides was observed. Thirteen novel miRNA candidates were predicted by alignment with the Brugia malayi genome. Eleven out of 13 predicted miRNA candidates were verified by using a PCR-based method. Target genes of the novel miRNA candidates were predicted by using the heartworm transcriptome dataset. To our knowledge, this is the first report of miRNA profiles in D. immitis, which will contribute to a better understanding of the complex biology of this zoonotic filarial nematode and the molecular regulation roles of miRNA involved. Our findings may also become a useful resource for small RNA studies in other filarial parasitic nematodes. PMID:23331513

  2. Implications of miRNAs in Colorectal Cancer Chemoresistance.

    PubMed

    Ju, Jingfang

    2011-01-01

    With the exponential growth of research efforts on non-coding microRNAs (miRNAs) in the past decade, miRNAs have been demonstrated to be important in many major human diseases, including diabetes, heart disease, and cancer. Due to the broad regulatory function of miRNAs, alterations of their expression can have profound consequences on multiple critical genes and pathways. One of the major issues related to the success of treating advanced colorectal cancer is chemoresistance. In this review, we will present some of the recent advancements in miRNA research related to chemoresistance mechanisms to 5-FU based chemotherapy in colorectal cancer and cancer stem cells. We believe that this miRNA-mediated resistance mechanism will offer novel strategies to develop future anti-cancer therapies.

  3. Assessment of proposed fighter agility metrics

    NASA Technical Reports Server (NTRS)

    Liefer, Randall K.; Valasek, John; Eggold, David P.; Downing, David R.

    1990-01-01

    This paper presents the results of an analysis of proposed metrics to assess fighter aircraft agility. A novel framework for classifying these metrics is developed and applied. A set of transient metrics intended to quantify the axial and pitch agility of fighter aircraft is evaluated with a high fidelity, nonlinear F-18 simulation. Test techniques and data reduction method are proposed, and sensitivities to pilot introduced errors during flight testing is investigated. Results indicate that the power onset and power loss parameters are promising candidates for quantifying axial agility, while maximum pitch up and pitch down rates are for quantifying pitch agility.

  4. Assay Reproducibility in Clinical Studies of Plasma miRNA

    PubMed Central

    Rice, Jonathan; Roberts, Henry; Burton, James; Pan, Jianmin; States, Vanessa; Rai, Shesh N.; Galandiuk, Susan

    2015-01-01

    There are increasing reports of plasma miRNAs as biomarkers of human disease but few standards in methodologic reporting, leading to inconsistent data. We systematically reviewed plasma miRNA studies published between July 2013-June 2014 to assess methodology. Six parameters were investigated: time to plasma extraction, methods of RNA extraction, type of miRNA, quantification, cycle threshold (Ct) setting, and methods of statistical analysis. We compared these data with a proposed standard methodologic technique. Beginning with initial screening for 380 miRNAs using microfluidic array technology and validation in an additional cohort of patients, we compared 11 miRNAs that exhibited differential expression between 16 patients with benign colorectal neoplasms (advanced adenomas) and 16 patients without any neoplasm (controls). Plasma was isolated immediately, 12, 24, 48, or 72 h following phlebotomy. miRNA was extracted using two different techniques (Trizol LS with pre-amplification or modified miRNeasy). We performed Taqman-based RT-PCR assays for the 11 miRNAs with subsequent analyses using a variable Ct setting or a fixed Ct set at 0.01, 0.03, 0.05, or 0.5. Assays were performed in duplicate by two different operators. RNU6 was the internal reference. Systematic review yielded 74 manuscripts meeting inclusion criteria. One manuscript (1.4%) documented all 6 methodological parameters, while < 5% of studies listed Ct setting. In our proposed standard technique, plasma extraction ≤12 h provided consistent ΔCt. miRNeasy extraction yielded higher miRNA concentrations and fewer non-expressed miRNAs compared to Trizol LS (1/704 miRNAs [0.14%] vs 109/704 miRNAs [15%], not expressed, respectively). A fixed Ct bar setting of 0.03 yielded the most reproducible data, provided that <10% miRNA were non-expressed. There was no significant intra-operator variability. There was significant inter-operator variation using Trizol LS extraction, while this was negligible using

  5. Elsevier Trophoblast Research Award Lecture: origin, evolution and future of placenta miRNAs.

    PubMed

    Morales-Prieto, D M; Ospina-Prieto, S; Schmidt, A; Chaiwangyen, W; Markert, U R

    2014-02-01

    MicroRNAs (miRNAs) regulate the expression of a large number of genes in plants and animals. Placental miRNAs appeared late in evolution and can be found only in mammals. Nevertheless, these miRNAs are constantly under evolutionary pressure. As a consequence, miRNA sequences and their mRNA targets may differ between species, and some miRNAs can only be found in humans. Their expression can be tissue- or cell-specific and can vary time-dependently. Human placenta tissue exhibits a specific miRNA expression pattern that dynamically changes during pregnancy and is reflected in the maternal plasma. Some placental miRNAs are involved in or associated with major pregnancy disorders, such as preeclampsia, intrauterine growth restriction or preterm delivery and, therefore, have a strong potential for usage as sensitive and specific biomarkers. In this review we summarize current knowledge on the origin of placental miRNAs, their expression in humans with special regard to trophoblast cells, interspecies differences, and their future as biomarkers. It can be concluded that animal models for human reproduction have a different panel of miRNAs and targets, and can only partly reflect or predict the situation in humans.

  6. Multiply-agile encryption in high speed communication networks

    SciTech Connect

    Pierson, L.G.; Witzke, E.L.

    1997-05-01

    Different applications have different security requirements for data privacy, data integrity, and authentication. Encryption is one technique that addresses these requirements. Encryption hardware, designed for use in high-speed communications networks, can satisfy a wide variety of security requirements if that hardware is key-agile, robustness-agile and algorithm-agile. Hence, multiply-agile encryption provides enhanced solutions to the secrecy, interoperability and quality of service issues in high-speed networks. This paper defines these three types of agile encryption. Next, implementation issues are discussed. While single-algorithm, key-agile encryptors exist, robustness-agile and algorithm-agile encryptors are still research topics.

  7. Teaching Agile Software Development: A Case Study

    ERIC Educational Resources Information Center

    Devedzic, V.; Milenkovic, S. R.

    2011-01-01

    This paper describes the authors' experience of teaching agile software development to students of computer science, software engineering, and other related disciplines, and comments on the implications of this and the lessons learned. It is based on the authors' eight years of experience in teaching agile software methodologies to various groups…

  8. The RITE Approach to Agile Acquisition

    DTIC Science & Technology

    2013-04-01

    Review (SVR), and Production Readiness Review ( PRR ), which were evaluated against Agile development requirements. Further analysis was conducted...Audit (FCA), PRR , Operational Test Readiness Review (OTRR), Physical Configuration Audit (PCA), Integration Readiness Review (IRR), In Service...Technology (DSB Task Force, 2009, p. 48) In the context of the primary milestone reviews (PDR, CDR, and SVR/ PRR ), a nominal Agile development structure was

  9. The Introduction of Agility into Albania.

    ERIC Educational Resources Information Center

    Smith-Stevens, Eileen J.; Shkurti, Drita

    1998-01-01

    Describes a plan to introduce and achieve a national awareness of agility (and easy entry into the world market) for Albania through the relatively stable higher-education order. Agility's four strategic principles are enriching the customer, cooperating to enhance competitiveness, organizing to master change and uncertainty, and leveraging the…

  10. An Agile Course-Delivery Approach

    ERIC Educational Resources Information Center

    Capellan, Mirkeya

    2009-01-01

    In the world of software development, agile methodologies have gained popularity thanks to their lightweight methodologies and flexible approach. Many advocates believe that agile methodologies can provide significant benefits if applied in the educational environment as a teaching method. The need for an approach that engages and motivates…

  11. Lipid Nanoparticles to Deliver miRNA in Cancer.

    PubMed

    Campani, Virginia; De Rosa, Giuseppe; Misso, Gabriella; Zarone, Mayra R; Grimaldi, Anna

    MicroRNAs (miRNAs) are a class of post-transcriptional gene expression modulators. In the past two decades, over 1500 human miRNAs were discovered. These small non-coding RNAs regulate various biological processes, including cell growth, proliferation, differentiation, and cell death. Thus, miRNAs have been proposed as new therapeutical agents in different multifactorial diseases such as cancer. Since miRNAs therapies represent a great promise, many research studies have been focused on the development of delivery strategies to overcome miRNAs biopharmaceutical issues. Lipid delivery systems are undoubtedly the non-viral carriers most largely investigated due to their biocompatibility, biodegradability, easy production, low toxicity and immunogenicity, possibility to easily modify the carriers for targeting strategies. In this mini-review we provide a rapid and updated overview on the lipid delivery system currently used to deliver miRNAs, pointing out the progresses achieved in the optimization of these nanovectors, which led up to the first clinical trial.

  12. Aberrant miRNA profiles associated with chronic benzene poisoning.

    PubMed

    Bai, Wenlin; Chen, Yujiao; Yang, Jing; Niu, Piye; Tian, Lin; Gao, Ai

    2014-06-01

    Chronic occupational benzene exposure is associated with an increased risk of hematological malignancies. To gain an insight into the new biomarkers and molecular mechanisms of chronic benzene poisoning, miRNA profiles and mRNA expression pattern from the peripheral blood mononuclear cells of chronic benzene poisoning patients and health controls matched age and gender without benzene exposure were performed using the Exiqon miRNA PCR ARRAY and Gene Chip Human Gene 2.0ST Arrays, respectively. Totally, 6 up-regulated miRNAs (miR-34a, miR-205, miR-10b, let-7d, miR-185 and miR-423-5p-2) and 7 down-regulated miRNAs (miR-133a, miR-543, hsa-miR-130a, miR-27b,miR-223, miR-142-5p and miR-320b) were found in chronic benzene poisoning group compared to health controls (P ≤ 0.05). By integrating miRNA and mRNA expression data, these differential miRNAs were mainly involved in regulation of transcription from RNA polymerase II promoter, axon guidance, regulation of transcription, DNA-dependent, nervous system development, and regulation of actin cytoskeleton organization. Further, pathway analysis indicated that SMAD4, PLCB1, NFAT5, GNAI2, PTEN, VEGFA, BCL2, CTNNB1 and CCND1 were key target genes of differential miRNAs which were implicated in Adherens junction, TGF-beta signaling pathway, Wnt signaling pathway, tight junction and Pathways in cancer. In conclusion, the aberrant miRNAs might be a potential biomarker of chronic benzene poisoning.

  13. Agile manufacturing from a statistical perspective

    SciTech Connect

    Easterling, R.G.

    1995-10-01

    The objective of agile manufacturing is to provide the ability to quickly realize high-quality, highly-customized, in-demand products at a cost commensurate with mass production. More broadly, agility in manufacturing, or any other endeavor, is defined as change-proficiency; the ability to thrive in an environment of unpredictable change. This report discusses the general direction of the agile manufacturing initiative, including research programs at the National Institute of Standards and Technology (NIST), the Department of Energy, and other government agencies, but focuses on agile manufacturing from a statistical perspective. The role of statistics can be important because agile manufacturing requires the collection and communication of process characterization and capability information, much of which will be data-based. The statistical community should initiate collaborative work in this important area.

  14. Fighter agility metrics, research, and test

    NASA Technical Reports Server (NTRS)

    Liefer, Randall K.; Valasek, John; Eggold, David P.

    1990-01-01

    Proposed new metrics to assess fighter aircraft agility are collected and analyzed. A framework for classification of these new agility metrics is developed and applied. A completed set of transient agility metrics is evaluated with a high fidelity, nonlinear F-18 simulation provided by the NASA Dryden Flight Research Center. Test techniques and data reduction methods are proposed. A method of providing cuing information to the pilot during flight test is discussed. The sensitivity of longitudinal and lateral agility metrics to deviations from the pilot cues is studied in detail. The metrics are shown to be largely insensitive to reasonable deviations from the nominal test pilot commands. Instrumentation required to quantify agility via flight test is also considered. With one exception, each of the proposed new metrics may be measured with instrumentation currently available. Simulation documentation and user instructions are provided in an appendix.

  15. Some Findings Concerning Requirements in Agile Methodologies

    NASA Astrophysics Data System (ADS)

    Rodríguez, Pilar; Yagüe, Agustín; Alarcón, Pedro P.; Garbajosa, Juan

    Agile methods have appeared as an attractive alternative to conventional methodologies. These methods try to reduce the time to market and, indirectly, the cost of the product through flexible development and deep customer involvement. The processes related to requirements have been extensively studied in literature, in most cases in the frame of conventional methods. However, conclusions of conventional methodologies could not be necessarily valid for Agile; in some issues, conventional and Agile processes are radically different. As recent surveys report, inadequate project requirements is one of the most conflictive issues in agile approaches and better understanding about this is needed. This paper describes some findings concerning requirements activities in a project developed under an agile methodology. The project intended to evolve an existing product and, therefore, some background information was available. The major difficulties encountered were related to non-functional needs and management of requirements dependencies.

  16. Agile manufacturing prototyping system (AMPS)

    SciTech Connect

    Garcia, P.

    1998-05-09

    The Agile Manufacturing Prototyping System (AMPS) is being integrated at Sandia National Laboratories. AMPS consists of state of the industry flexible manufacturing hardware and software enhanced with Sandia advancements in sensor and model based control; automated programming, assembly and task planning; flexible fixturing; and automated reconfiguration technology. AMPS is focused on the agile production of complex electromechanical parts. It currently includes 7 robots (4 Adept One, 2 Adept 505, 1 Staubli RX90), conveyance equipment, and a collection of process equipment to form a flexible production line capable of assembling a wide range of electromechanical products. This system became operational in September 1995. Additional smart manufacturing processes will be integrated in the future. An automated spray cleaning workcell capable of handling alcohol and similar solvents was added in 1996 as well as parts cleaning and encapsulation equipment, automated deburring, and automated vision inspection stations. Plans for 1997 and out years include adding manufacturing processes for the rapid prototyping of electronic components such as soldering, paste dispensing and pick-and-place hardware.

  17. CT-assisted agile manufacturing

    NASA Astrophysics Data System (ADS)

    Stanley, James H.; Yancey, Robert N.

    1996-11-01

    The next century will witness at least two great revolutions in the way goods are produced. First, workers will use the medium of virtual reality in all aspects of marketing, research, development, prototyping, manufacturing, sales and service. Second, market forces will drive manufacturing towards small-lot production and just-in-time delivery. Already, we can discern the merging of these megatrends into what some are calling agile manufacturing. Under this new paradigm, parts and processes will be designed and engineered within the mind of a computer, tooled and manufactured by the offspring of today's rapid prototyping equipment, and evaluated for performance and reliability by advanced nondestructive evaluation (NDE) techniques and sophisticated computational models. Computed tomography (CT) is the premier example of an NDE method suitable for future agile manufacturing activities. It is the only modality that provides convenient access to the full suite of engineering data that users will need to avail themselves of computer- aided design, computer-aided manufacturing, and computer- aided engineering capabilities, as well as newly emerging reverse engineering, rapid prototyping and solid freeform fabrication technologies. As such, CT is assured a central, utilitarian role in future industrial operations. An overview of this exciting future for industrial CT is presented.

  18. Novel miRNA-31 and miRNA-200a-Mediated Regulation of Retinoblastoma Proliferation

    PubMed Central

    Montoya, Vanessa; Fan, Hanli; Bryar, Paul J.; Weinstein, Joanna L.; Mets, Marilyn B.; Feng, Gang; Martin, Joshua; Martin, Alissa; Jiang, Hongmei; Laurie, Nikia A.

    2015-01-01

    Retinoblastoma is the most common intraocular tumor in children. Current management includes broad-based treatments such as chemotherapy, enucleation, laser therapy, or cryotherapy. However, therapies that target specific pathways important for retinoblastoma progression could provide valuable alternatives for treatment. MicroRNAs are short, noncoding RNA transcripts that can regulate the expression of target genes, and their aberrant expression often facilitates disease. The identification of post-transcriptional events that occur after the initiating genetic lesions could further define the rapidly aggressive growth displayed by retinoblastoma tumors. In this study, we used two phenotypically different retinoblastoma cell lines to elucidate the roles of miRNA-31 and miRNA-200a in tumor proliferation. Our approach confirmed that miRNAs-31 and -200a expression is significantly reduced in human retinoblastomas. Moreover, overexpression of these two miRNAs restricts the expansion of a highly proliferative cell line (Y79), but does not restrict the growth rate of a less aggressive cell line (Weri1). Gene expression profiling of miRNA-31 and/or miRNA-200a-overexpressing cells identified differentially expressed mRNAs associated with the divergent response of the two cell lines. This work has the potential to enhance the development of targeted therapeutic approaches for retinoblastoma and improve the efficacy of treatment. PMID:26379276

  19. Platelet miRNAs and cardiovascular diseases.

    PubMed

    Fuentes, Eduardo; Palomo, Iván; Alarcón, Marcelo

    2015-07-15

    Activated platelets play a critical role in the acute complications of atherosclerosis that cause life-threatening ischemic events at late stages of the disease. The miRNAs are a novel class of small, non-coding RNAs that play a significant role in both inflammatory and cardiovascular diseases. The miRNAs are known to be present in platelets and exert important regulatory functions. Here we systematically examine the genes that are regulated by platelet miRNAs (miRNA-223,miRNA-126,miRNA-21, miRNA-24 and miRNA-197) and the association with cardiovascular disease risks. Platelet-secreted miRNAs could be novel biomarkers associated with cardiovascular diseases.

  20. miRNAs as biomarkers in colorectal cancer diagnosis and prognosis.

    PubMed

    Ju, Jingfang

    2010-05-01

    Since the discovery of noncoding small miRNAs and their function in controlling mRNA translational rate, the small non-coding miRNA world has become a research wonderland for cancer and other human diseases. Due to the critical regulatory function, miRNA can act as an oncogene or a tumor-suppressor gene. This review will cover some of the recent discoveries of the potential of miRNAs as cancer biomarkers in colorectal cancer, future challenges and solutions.

  1. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes.

    PubMed

    Baskerville, Scott; Bartel, David P

    2005-03-01

    MicroRNAs (miRNAs) are short endogenous RNAs known to post-transcriptionally repress gene expression in animals and plants. A microarray profiling survey revealed the expression patterns of 175 human miRNAs across 24 different human organs. Our results show that proximal pairs of miRNAs are generally coexpressed. In addition, an abrupt transition in the correlation between pairs of expressed miRNAs occurs at a distance of 50 kb, implying that miRNAs separated by <50 kb typically derive from a common transcript. Some microRNAs are within the introns of host genes. Intronic miRNAs are usually coordinately expressed with their host gene mRNA, implying that they also generally derive from a common transcript, and that in situ analyses of host gene expression can be used to probe the spatial and temporal localization of intronic miRNAs.

  2. Mutant p53 inhibits miRNA biogenesis by interfering with the microprocessor complex.

    PubMed

    Garibaldi, F; Falcone, E; Trisciuoglio, D; Colombo, T; Lisek, K; Walerych, D; Del Sal, G; Paci, P; Bossi, G; Piaggio, G; Gurtner, A

    2016-07-21

    Downregulation of microRNAs (miRNAs) is commonly observed in cancers and promotes tumorigenesis suggesting that miRNAs may function as tumor suppressors. However, the mechanism through which miRNAs are regulated in cancer, and the connection between oncogenes and miRNA biogenesis remain poorly understood. The TP53 tumor-suppressor gene is mutated in half of human cancers resulting in an oncogene with gain-of-function activities. Here we demonstrate that mutant p53 (mutp53) oncoproteins modulate the biogenesis of a subset of miRNAs in cancer cells inhibiting their post-transcriptional maturation. Interestingly, among these miRNAs several are also downregulated in human tumors. By confocal, co-immunoprecipitation and RNA-chromatin immunoprecipitation experiments, we show that endogenous mutp53 binds and sequesters RNA helicases p72/82 from the microprocessor complex, interfering with Drosha-pri-miRNAs association. In agreement with this, the overexpression of p72 leads to an increase of mature miRNAs levels. Moreover, functional experiments demonstrate the oncosuppressive role of mutp53-dependent miRNAs (miR-517a, -519a, -218, -105). Our study highlights a previously undescribed mechanism by which mutp53 interferes with Drosha-p72/82 association leading, at least in part, to miRNA deregulation observed in cancer.

  3. Developing communications requirements for Agile Product Realization

    SciTech Connect

    Forsythe, C.; Ashby, M.R.

    1994-03-01

    Sandia National Laboratories has undertaken the Agile Product Realization for Innovative electroMEchanical Devices (A-PRIMED) pilot project to develop and implement technologies for agile design and manufacturing of electrochemical components. Emphasis on information-driven processes, concurrent engineering and multi-functional team communications makes computer-supported cooperative work critical to achieving significantly faster product development cycles. This report describes analyses conducted in developing communications requirements and a communications plan that addresses the unique communications demands of an agile enterprise.

  4. Agile Leaders, Agile Institutions: Educating Adaptive and Innovative Leaders for Today and Tomorrow

    DTIC Science & Technology

    2005-03-18

    to organizational learning , specifically for militaries at war. With these lenses and informed by observations from the CCCs, the paper advances...rapid, effective organizational learning is the essence of organizational agility. In line with this paper’s concept of individual agility...organizational agility is a metaphor for organizational learning that is faster, more flexible, and more sensitive to the speed with which individual experiential

  5. Test Methods for Robot Agility in Manufacturing

    PubMed Central

    Downs, Anthony; Harrison, William; Schlenoff, Craig

    2017-01-01

    Purpose The paper aims to define and describe test methods and metrics to assess industrial robot system agility in both simulation and in reality. Design/methodology/approach The paper describes test methods and associated quantitative and qualitative metrics for assessing robot system efficiency and effectiveness which can then be used for the assessment of system agility. Findings The paper describes how the test methods were implemented in a simulation environment and real world environment. It also shows how the metrics are measured and assessed as they would be in a future competition. Practical Implications The test methods described in this paper will push forward the state of the art in software agility for manufacturing robots, allowing small and medium manufacturers to better utilize robotic systems. Originality / value The paper fulfills the identified need for standard test methods to measure and allow for improvement in software agility for manufacturing robots. PMID:28203034

  6. Agile manufacturing concepts and opportunities in ceramics

    SciTech Connect

    Booth, C.L.; Harmer, M.P.

    1995-08-01

    In 1991 Lehigh University facilitated seminars over a period of 8 months to define manufacturing needs for the 21st century. They concluded that the future will be characterized by rapid changes in technology advances, customer demands, and shifts in market dynamics and coined the term {open_quotes}Agile Manufacturing{close_quotes}. Agile manufacturing refers to the ability to thrive in an environment of constant unpredictable change. Market opportunities are attacked by partnering to form virtual firms to dynamically obtain the required skills for each product opportunity. This paper will describe and compare agile vs. traditional concepts of organization & structure, management policy and ethics, employee environment, product focus, information, and paradigm shift. Examples of agile manufacturing applied to ceramic materials will be presented.

  7. Identification of associations between small molecule drugs and miRNAs based on functional similarity

    PubMed Central

    Dai, EnYu; Yang, Feng; Wang, Shuyuan; Chen, Xiaowen; Yang, Lei; Wang, Yuwen; Jiang, Wei

    2016-01-01

    MicroRNAs (miRNAs) are a class of small non-coding RNA molecules that regulate gene expression at post-transcriptional level. Increasing evidences show aberrant expression of miRNAs in varieties of diseases. Targeting the dysregulated miRNAs with small molecule drugs has become a novel therapy for many human diseases, especially cancer. Here, we proposed a novel computational approach to identify associations between small molecules and miRNAs based on functional similarity of differentially expressed genes. At the significance level of p < 0.01, we constructed the small molecule and miRNA functional similarity network involving 111 small molecules and 20 miRNAs. Moreover, we also predicted associations between drugs and diseases through integrating our identified small molecule-miRNA associations with experimentally validated disease related miRNAs. As a result, we identified 2265 associations between FDA approved drugs and diseases, in which ~35% associations have been validated by comprehensive literature reviews. For breast cancer, we identified 19 potential drugs, in which 12 drugs were supported by previous studies. In addition, we performed survival analysis for the patients from TCGA and GEO database, which indicated that the associated miRNAs of 4 drugs might be good prognosis markers in breast cancer. Collectively, this study proposed a novel approach to predict small molecule and miRNA associations based on functional similarity, which may pave a new way for miRNA-targeted therapy and drug repositioning. PMID:27232942

  8. Expressional analysis of immune-related miRNAs in breast milk.

    PubMed

    Na, R S; E, G X; Sun, W; Sun, X W; Qiu, X Y; Chen, L P; Huang, Y F

    2015-09-25

    Immune-related miRNAs in breast milk are extracellular miRNAs that are related to immune organ development and regulation of the immune function in infants and young animals. The goal of this study was to compare the expression levels of five immune-related miRNAs in breast milk in black goats, humans, and dairy cattle. The miRNAs from milk were extracted and the expression levels were assessed using quantitive RT-PCR methods. MiR-146, miR-155, miR-181a, miR-223, and miR-150 were all detected in Dazu black goat milk, and these miRNAs were significantly more highly expressed in colostrum than in mature milk of goats (P < 0.01), except for miR-150. Further, all five miRNAs were expressed in human colostrum, but patterns differed from those in goats: miR-146 and miR-155 were highly expressed (P < 0.01) in human colostrum, whereas miR-223 was abundant in goat colostrum (P < 0.01). In addition, five miRNAs were significantly higher in bovine mature milk than in goat milk (P < 0.01). Taken together, these results confirm that immune-related miRNAs are rich in breast milk with different expression levels depending on the lactation phase and species.

  9. Agile Port and High Speed Ship Technologies

    DTIC Science & Technology

    2009-12-31

    Report PNW Agile Port System Demonstration Center for the Commercial Deployment of Transportation Technologies milestone agenda for accomplishing the... report summarizes the results of the remaining three projects in the FY05 program cycle, in particular the PNW Agile Port System Demonstration, a system...the accomplishment of each project and the program objectives. With the submission of this report the FY05 CCDoTT Program is complete. Bibliography

  10. SuperAGILE Services at ASDC

    SciTech Connect

    Preger, B.; Verrecchia, F.; Pittori, C.; Antonelli, L. A.; Giommi, P.; Lazzarotto, F.; Evangelista, Y.

    2008-05-22

    The Italian Space Agency Science Data Center (ASDC) is a facility with several responsibilities including support to all the ASI scientific missions as for management and archival of the data, acting as the interface between ASI and the scientific community and providing on-line access to the data hosted. In this poster we describe the services that ASDC provides for SuperAGILE, in particular the ASDC public web pages devoted to the dissemination of SuperAGILE scientific results. SuperAGILE is the X-Ray imager onboard the AGILE mission, and provides the scientific community with orbit-by-orbit information on the observed sources. Crucial source information including position and flux in chosen energy bands will be reported in the SuperAGILE public web page at ASDC. Given their particular interest, another web page will be dedicated entirely to GRBs and other transients, where new event alerts will be notified and where users will find all the available informations on the GRBs detected by SuperAGILE.

  11. Role of Alix in miRNA packaging during extracellular vesicle biogenesis

    PubMed Central

    IAVELLO, ALESSANDRA; FRECH, VALESKA S.L.; GAI, CHIARA; DEREGIBUS, MARIA CHIARA; QUESENBERRY, PETER J.; CAMUSSI, GIOVANNI

    2016-01-01

    Evidence indicates that Alix, an accessory protein of the endosomal sorting complex required for transport (ESCRT), is involved in the biogenesis of extracellular vesicles (EVs). EVs contain selected patterns of microRNAs (miRNAs or miRs); however, little is known about the mechanisms of miRNA enrichment in EVs. The aim of the present study was to evaluate whether Alix is involved in the packaging of miRNAs within EVs released by human liver stem-like cells (HLSCs). EVs released from HLSCs were enriched with miRNAs and expressed Alix and several RNA-binding proteins, including Argonaute 2 (Ago2), a member of the Argonaute family known to be involved in the transport and the processing of miRNAs. Co-immunoprecipitation experiments revealed an association between Alix and Ago2. The results from RT-qPCR indicated that in the Alix/Ago2 immunoprecipitates, miRNAs were detectable. EVs were instrumental in transferring selected miRNAs from HLSCs to human endothelial cells absent in the latter cells. Alix knockdown did not influence the number of EVs released by HLSCs, but it significantly decreased miRNA expression levels in the EVs and consequently their transfer to the endothelium. Our findings indicate that Alix binds to Ago2 and miRNAs, suggesting that it plays a key role in miRNA enrichment during EV biogenesis. These results may represent a novel function of Alix, demonstrating its involvement in the EV-mediated transfer of miRNAs. PMID:26935291

  12. In silico screening of alleged miRNAs associated with cell competition: an emerging cellular event in cancer.

    PubMed

    Patel, Manish; Antala, Bhavesh; Shrivastava, Neeta

    2015-12-01

    Cell competition is identified as a crucial phenomenon for cancer and organ development. There is a possibility that microRNAs (miRNAs) may play an important role in the regulation of expression of genes involved in cell competition. In silico screening of miRNAs is an effort to abridge, economize and expedite the experimental approaches to identification of potential miRNAs involved in cell competition, as no study has reported involvement of miRNAs in cell competition to date. In this study, we used multiple screening steps as follows: (i) selection of cell competition related genes of Drosophila through a literature survey; (ii) homology study of selected cell competition related genes; (iii) identification of miRNAs that target conserved cell competition-related genes through prediction tools; (iv) sequence conservation analysis of identified miRNAs with human genome; (v) identification of conserved cell competition miRNAs using their expression profiles and exploration of roles of their homologous human miRNAs. This study led to the identification of nine potential cell competition miRNAs in the Drosophila genome. Importantly, eighteen human homologs of these nine potential Drosophila miRNAs are well reported for their involvement in different types of cancers. This confirms their probable involvement in cell competition as well, because cell competition is well justified for its involvement in cancer initiation and maintenance.

  13. Methods and matrices: approaches to identifying miRNAs for Nasopharyngeal carcinoma

    PubMed Central

    2014-01-01

    Background Nasopharyngeal carcinoma (NPC) is a solid tumor of the head and neck. Multimodal therapy is highly effective when NPC is detected early. However, due to the location of the tumor and the absence of clinical signs, early detection is difficult, making a biomarker for the early detection of NPC a priority. The dysregulation of small non-coding RNAs (miRNAs) during carcinogenesis is the focus of much current biomarker research. Herein, we examine several miRNA discovery methods using two sample matrices to identify circulating miRNAs (c-miRNAs) associated with NPC. Methods We tested two miRNA discovery workflows on two sample sources for miRNAs associated with NPC. In the first workflow, we assumed that NPC tumor tissue would be enriched for miRNAs, so we compared miRNA expression in FFPE from NPC cases and controls using microarray and RNA-Seq technologies. Candidate miRNAs from both technologies were verified by qPCR in FFPE and sera from an independent NPC sample set. In a second workflow, we directly interrogated NPC case and control sera by RNA-Seq for c-miRNAs associated with NPC, with candidate c-miRNAs verified by qPCR in the sera from the same independent NPC sample set. Results Both microarray and RNA-Seq narrowed the miRNA signature to 1-5% of the known mature human miRNAs. Moreover, these two methods produced similar results when applied to the same sample type (FFPE), with RNA-Seq additionally indicating “unknown” miRNAs associated with NPC. However, we found different miRNA profiles in NPC sera compared to FFPE using RNA-Seq, with the few overlapping miRNAs found to be significantly up-regulated in FFPE significantly down-regulated in sera (and vice versa). Despite the different miRNA profiles found in FFPE and sera, both profiles strongly associated with NPC, providing two potential sources for biomarker signatures for NPC. Conclusions We determined that the direct interrogation of sera by RNA-Seq was the most informative method for

  14. miRNA Profiles in Plasma from Patients with Sleep Disorders Reveal Dysregulation of miRNAs in Narcolepsy and Other Central Hypersomnias

    PubMed Central

    Holm, Anja; Bang-Berthelsen, Claus Heiner; Knudsen, Stine; Kornum, Birgitte R.; Modvig, Signe; Jennum, Poul; Gammeltoft, Steen

    2014-01-01

    Study Objectives: MicroRNAs (miRNAs) have been implicated in the pathogenesis of human diseases including neurological disorders. The aim is to address the involvement of miRNAs in the pathophysiology of central hypersomnias including autoimmune narcolepsy with cataplexy and hypocretin deficiency (type 1 narcolepsy), narcolepsy without cataplexy (type 2 narcolepsy), and idiopathic hypersomnia. Design: We conducted high-throughput analysis of miRNA in plasma from three groups of patients—with type 1 narcolepsy, type 2 narcolepsy, and idiopathic hypersomnia, respectively—in comparison with healthy controls using quantitative real-time polymerase chain reaction (qPCR) panels. Setting: University hospital based sleep clinic and research laboratories. Patients: Twelve patients with type 1 narcolepsy, 12 patients with type 2 narcolepsy, 12 patients with idiopathic hypersomnia, and 12 healthy controls. Measurements and Results: By analyzing miRNA in plasma with qPCR we identified 50, 24, and 6 miRNAs that were different in patients with type 1 narcolepsy, type 2 narcolepsy, and idiopathic hypersomnia, respectively, compared with healthy controls. Twenty miRNA candidates who fulfilled the criteria of at least two-fold difference and p-value < 0.05 were selected to validate the miRNA changes in an independent cohort of patients. Four miRNAs differed significantly between type 1 narcolepsy patients and healthy controls. Levels of miR-30c, let-7f, and miR-26a were higher, whereas the level of miR-130a was lower in type 1 narcolepsy than healthy controls. The miRNA differences were not specific for type 1 narcolepsy, since the levels of the four miRNAs were also altered in patients with type 2 narcolepsy and idiopathic hypersomnia compared with healthy controls. Conclusion: The levels of four miRNAs differed in plasma from patients with type 1 narcolepsy, type 2 narcolepsy and idiopathic hypersomnia suggesting that alterations of miRNAs may be involved in the

  15. Software ``Best'' Practices: Agile Deconstructed

    NASA Astrophysics Data System (ADS)

    Fraser, Steven

    Software “best” practices depend entirely on context - in terms of the problem domain, the system constructed, the software designers, and the “customers” ultimately deriving value from the system. Agile practices no longer have the luxury of “choosing” small non-mission critical projects with co-located teams. Project stakeholders are selecting and adapting practices based on a combina tion of interest, need and staffing. For example, growing product portfolios through a merger or the acquisition of a company exposes legacy systems to new staff, new software integration challenges, and new ideas. Innovation in communications (tools and processes) to span the growth and contraction of both information and organizations, while managing the adoption of changing software practices, is imperative for success. Traditional web-based tools such as web pages, document libraries, and forums are not suf ficient. A blend of tweeting, blogs, wikis, instant messaging, web-based confer encing, and telepresence creates a new dimension of communication “best” practices.

  16. miRNAs regulated by estrogens, tamoxifen, and endocrine disruptors and their downstream gene targets

    PubMed Central

    Klinge, Carolyn M.

    2015-01-01

    MicroRNAs (miRNAs) are short (22 nucleotides), single-stranded, non-coding RNAs that form complimentary base-pairs with the 3’ untranslated region of target mRNAs within the RNA-induced silencing complex (RISC) and block translation and/or stimulate mRNA transcript degradation. The non-coding miRBase (release 21, June 2014) reports that human genome contains ~2,588 mature miRNAs which regulate ~ 60% of human protein-coding mRNAs. Dysregulation of miRNA expression has been implicated in estrogen-related diseases including breast and endometrial cancers. The mechanism for estrogen regulation of miRNA expression and the role of estrogen-regulated miRNAs in normal homeostasis, reproduction, lactation, and in cancer is an area of great research and clinical interest. Estrogens regulate miRNAs transcription through estrogen receptors α and β in a tissue-specific and cell-dependent manner. This review focuses primary on the regulation of miRNA expression by ligand-activated ERs and their bona fide gene targets and includes miRNAs regulation by tamoxifen and endocrine disrupting chemicals (EDCs) in breast cancer and cell lines. PMID:25659536

  17. miRNAs in brain development

    SciTech Connect

    Petri, Rebecca; Malmevik, Josephine; Fasching, Liana; Åkerblom, Malin; Jakobsson, Johan

    2014-02-01

    MicroRNAs (miRNAs) are small, non-coding RNAs that negatively regulate gene expression at the post-transcriptional level. In the brain, a large number of miRNAs are expressed and there is a growing body of evidence demonstrating that miRNAs are essential for brain development and neuronal function. Conditional knockout studies of the core components in the miRNA biogenesis pathway, such as Dicer and DGCR8, have demonstrated a crucial role for miRNAs during the development of the central nervous system. Furthermore, mice deleted for specific miRNAs and miRNA-clusters demonstrate diverse functional roles for different miRNAs during the development of different brain structures. miRNAs have been proposed to regulate cellular functions such as differentiation, proliferation and fate-determination of neural progenitors. In this review we summarise the findings from recent studies that highlight the importance of miRNAs in brain development with a focus on the mouse model. We also discuss the technical limitations of current miRNA studies that still limit our understanding of this family of non-coding RNAs and propose the use of novel and refined technologies that are needed in order to fully determine the impact of specific miRNAs in brain development. - Highlights: • miRNAs are essential for brain development and neuronal function. • KO of Dicer is embryonically lethal. • Conditional Dicer KO results in defective proliferation or increased apoptosis. • KO of individual miRNAs or miRNA families is necessary to determine function.

  18. miRNA Digger: a comprehensive pipeline for genome-wide novel miRNA mining.

    PubMed

    Yu, Lan; Shao, Chaogang; Ye, Xinghuo; Meng, Yijun; Zhou, Yincong; Chen, Ming

    2016-01-06

    MicroRNAs (miRNAs) are important regulators of gene expression. The recent advances in high-throughput sequencing (HTS) technique have greatly facilitated large-scale detection of the miRNAs. However, thoroughly discovery of novel miRNAs from the available HTS data sets remains a major challenge. In this study, we observed that Dicer-mediated cleavage sites for the processing of the miRNA precursors could be mapped by using degradome sequencing data in both animals and plants. In this regard, a novel tool, miRNA Digger, was developed for systematical discovery of miRNA candidates through genome-wide screening of cleavage signals based on degradome sequencing data. To test its sensitivity and reliability, miRNA Digger was applied to discover miRNAs from four organs of Arabidopsis. The results revealed that a majority of already known mature miRNAs along with their miRNA*s expressed in these four organs were successfully recovered. Notably, a total of 30 novel miRNA-miRNA* pairs that have not been registered in miRBase were discovered by miRNA Digger. After target prediction and degradome sequencing data-based validation, eleven miRNA-target interactions involving six of the novel miRNAs were identified. Taken together, miRNA Digger could be applied for sensitive detection of novel miRNAs and it could be freely downloaded from http://www.bioinfolab.cn/miRNA_Digger/index.html.

  19. Fighter agility metrics. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Liefer, Randall K.

    1990-01-01

    Fighter flying qualities and combat capabilities are currently measured and compared in terms relating to vehicle energy, angular rates and sustained acceleration. Criteria based on these measurable quantities have evolved over the past several decades and are routinely used to design aircraft structures, aerodynamics, propulsion and control systems. While these criteria, or metrics, have the advantage of being well understood, easily verified and repeatable during test, they tend to measure the steady state capability of the aircraft and not its ability to transition quickly from one state to another. Proposed new metrics to assess fighter aircraft agility are collected and analyzed. A framework for classification of these new agility metrics is developed and applied. A complete set of transient agility metrics is evaluated with a high fidelity, nonlinear F-18 simulation. Test techniques and data reduction methods are proposed. A method of providing cuing information to the pilot during flight test is discussed. The sensitivity of longitudinal and lateral agility metrics to deviations from the pilot cues is studied in detail. The metrics are shown to be largely insensitive to reasonable deviations from the nominal test pilot commands. Instrumentation required to quantify agility via flight test is also considered. With one exception, each of the proposed new metrics may be measured with instrumentation currently available.

  20. Gamma-ray Astrophysics with AGILE

    SciTech Connect

    Longo, Francesco |; Tavani, M.; Barbiellini, G.; Argan, A.; Basset, M.; Boffelli, F.; Bulgarelli, A.; Caraveo, P.; Cattaneo, P.; Chen, A.; Costa, E.; Del Monte, E.; Di Cocco, G.; Di Persio, G.; Donnarumma, I.; Feroci, M.; Fiorini, M.; Foggetta, L.; Froysland, T.; Frutti, M.

    2007-07-12

    AGILE will explore the gamma-ray Universe with a very innovative instrument combining for the first time a gamma-ray imager and a hard X-ray imager. AGILE will be operational in spring 2007 and it will provide crucial data for the study of Active Galactic Nuclei, Gamma-Ray Bursts, unidentified gamma-ray sources. Galactic compact objects, supernova remnants, TeV sources, and fundamental physics by microsecond timing. The AGILE instrument is designed to simultaneously detect and image photons in the 30 MeV - 50 GeV and 15 - 45 keV energy bands with excellent imaging and timing capabilities, and a large field of view covering {approx} 1/5 of the entire sky at energies above 30 MeV. A CsI calorimeter is capable of GRB triggering in the energy band 0.3-50 MeV AGILE is now (March 2007) undergoing launcher integration and testing. The PLSV launch is planned in spring 2007. AGILE is then foreseen to be fully operational during the summer of 2007.

  1. Enterprise Technologies Deployment for Agile Manufacturing

    SciTech Connect

    Neal, R.E.

    1992-11-01

    This report is intended for high-level technical planners who are responsible for planning future developments for their company or Department of Energy/Defense Programs (DOE/DP) facilities. On one hand, the information may be too detailed or contain too much manufacturing technology jargon for a high-level, nontechnical executive, while at the same time an expert in any of the four infrastructure fields (Product Definition/Order Entry, Planning and Scheduling, Shop Floor Management, and Intelligent Manufacturing Systems) will know more than is conveyed here. The purpose is to describe a vision of technology deployment for an agile manufacturing enterprise. According to the 21st Century Manufacturing Enterprise Strategy, the root philosophy of agile manufacturing is that ``competitive advantage in the new systems will belong to agile manufacturing enterprises, capable of responding rapidly to demand for high-quality, highly customized products.`` Such agility will be based on flexible technologies, skilled workers, and flexible management structures which collectively will foster cooperative initiatives in and among companies. The remainder of this report is dedicated to sharpening our vision and to establishing a framework for defining specific project or pre-competitive project goals which will demonstrate agility through technology deployment.

  2. Enterprise Technologies Deployment for Agile Manufacturing

    SciTech Connect

    Neal, R.E.

    1992-11-01

    This report is intended for high-level technical planners who are responsible for planning future developments for their company or Department of Energy/Defense Programs (DOE/DP) facilities. On one hand, the information may be too detailed or contain too much manufacturing technology jargon for a high-level, nontechnical executive, while at the same time an expert in any of the four infrastructure fields (Product Definition/Order Entry, Planning and Scheduling, Shop Floor Management, and Intelligent Manufacturing Systems) will know more than is conveyed here. The purpose is to describe a vision of technology deployment for an agile manufacturing enterprise. According to the 21st Century Manufacturing Enterprise Strategy, the root philosophy of agile manufacturing is that competitive advantage in the new systems will belong to agile manufacturing enterprises, capable of responding rapidly to demand for high-quality, highly customized products.'' Such agility will be based on flexible technologies, skilled workers, and flexible management structures which collectively will foster cooperative initiatives in and among companies. The remainder of this report is dedicated to sharpening our vision and to establishing a framework for defining specific project or pre-competitive project goals which will demonstrate agility through technology deployment.

  3. Altered miRNA expression in the cervix during pregnancy associated with lead and mercury exposure

    PubMed Central

    Sanders, Alison P; Burris, Heather H; Just, Allan C; Motta, Valeria; Amarasiriwardena, Chitra; Svensson, Katherine; Oken, Emily; Solano-Gonzalez, Maritsa; Mercado-Garcia, Adriana; Pantic, Ivan; Schwartz, Joel; Tellez-Rojo, Martha M; Baccarelli, Andrea A; Wright, Robert O

    2015-01-01

    Aim: Toxic metals including lead and mercury are associated with adverse pregnancy outcomes. This study aimed to assess the association between miRNA expression in the cervix during pregnancy with lead and mercury levels. Materials & methods: We obtained cervical swabs from pregnant women (n = 60) and quantified cervical miRNA expression. Women's blood lead, bone lead and toenail mercury levels were analyzed. We performed linear regression to examine the association between metal levels and expression of 74 miRNAs adjusting for covariates. Results: Seventeen miRNAs were negatively associated with toenail mercury levels, and tibial bone lead levels were associated with decreased expression of miR-575 and miR-4286. Conclusion: The findings highlight miRNAs in the human cervix as novel responders to maternal chemical exposure during pregnancy. PMID:26418635

  4. Bioinformatics of cardiovascular miRNA biology.

    PubMed

    Kunz, Meik; Xiao, Ke; Liang, Chunguang; Viereck, Janika; Pachel, Christina; Frantz, Stefan; Thum, Thomas; Dandekar, Thomas

    2015-12-01

    MicroRNAs (miRNAs) are small ~22 nucleotide non-coding RNAs and are highly conserved among species. Moreover, miRNAs regulate gene expression of a large number of genes associated with important biological functions and signaling pathways. Recently, several miRNAs have been found to be associated with cardiovascular diseases. Thus, investigating the complex regulatory effect of miRNAs may lead to a better understanding of their functional role in the heart. To achieve this, bioinformatics approaches have to be coupled with validation and screening experiments to understand the complex interactions of miRNAs with the genome. This will boost the subsequent development of diagnostic markers and our understanding of the physiological and therapeutic role of miRNAs in cardiac remodeling. In this review, we focus on and explain different bioinformatics strategies and algorithms for the identification and analysis of miRNAs and their regulatory elements to better understand cardiac miRNA biology. Starting with the biogenesis of miRNAs, we present approaches such as LocARNA and miRBase for combining sequence and structure analysis including phylogenetic comparisons as well as detailed analysis of RNA folding patterns, functional target prediction, signaling pathway as well as functional analysis. We also show how far bioinformatics helps to tackle the unprecedented level of complexity and systemic effects by miRNA, underlining the strong therapeutic potential of miRNA and miRNA target structures in cardiovascular disease. In addition, we discuss drawbacks and limitations of bioinformatics algorithms and the necessity of experimental approaches for miRNA target identification. This article is part of a Special Issue entitled 'Non-coding RNAs'.

  5. Neuropilin-1 is a receptor for extracellular miRNA and AGO2/miRNA complexes and mediates the internalization of miRNAs that modulate cell function

    PubMed Central

    Prud'homme, Gerald J.; Glinka, Yelena; Lichner, Zsuzsanna; Yousef, George M.

    2016-01-01

    Extracellular miRNAs are increasingly studied as markers for specific diseases. They are released in biological fluids in a remarkably stable form, and may play a role in intercellular communication. They are thought to be protected against degradation by either encapsulation within microparticles, or by binding to proteins (mostly AGO2). The particulate forms may be internalized by endocytosis or membrane fusion, but the protein-bound forms require a receptor mechanism for their uptake. A major question is whether there are natural cell-membrane receptors that capture and internalize protein-bound functional miRNAs. We examined neuropilin-1 (NRP1), in view of its properties as a receptor for many ligands, including growth factors such as vascular endothelial growth factor (VEGF), and efficiency at mediating ligand internalization. It is expressed by endothelial cells, many other normal cell types, and cancer cells. Here, we report that NRP1 binds miRNAs with high affinity, and promotes their entry into the cell. Furthermore, the internalized miRNAs remain functional, as they specifically regulate proliferation and migration of cancer cells, as well as tube formation by human endothelial cells. Anti-NRP1 antibodies or NRP1 siRNA knockdown block miRNA effects, further confirming NRP1-mediated uptake. VEGF does not compete with miRNAs for binding to NRP1. In addition, NRP1 binds extracellular AGO2 (carrying miRNA or not), and internalizes AGO2/miRNA complexes. Because miRNA bound to AGO2 appears to the most abundant form in body fluids, this may have important physiological and pathological effects. PMID:27486976

  6. Humans and Their Impact on Cyber Agility

    DTIC Science & Technology

    2012-06-01

    Figure B-1: Hierarchical View of Measures of Effectiveness19 Where: MoM = Set of variables that focus the assessment on the issues of interest...and see a story about incest , one might be offended at the very thought while others would not be as shocked because it is "natural" for their way

  7. Dissecting the regulation rules of cancer-related miRNAs based on network analysis

    PubMed Central

    Liu, Zhongyu; Guo, Yanzhi; Pu, Xuemei; Li, Menglong

    2016-01-01

    miRNAs (microRNAs) are a set of endogenous and small non-coding RNAs which specifically induce degradation of target mRNAs or inhibit protein translation to control gene expression. Obviously, aberrant miRNA expression in human cells will lead to a serious of changes in protein-protein interaction network (PPIN), thus to activate or inactivate some pathways related to various diseases, especially carcinogenesis. In this study, we systematically constructed the miRNA-regulated co-expressed protein-protein interaction network (CePPIN) for 17 cancers firstly. We investigated the topological parameters and functional annotation for the proteins in CePPIN, especially for those miRNA targets. We found that targets regulated by more miRNAs tend to play a more important role in the forming process of cancers. We further elucidated the miRNA regulation rules in PPIN from a more systematical perspective. By GO and KEGG pathway analysis, miRNA targets are involved in various cellular processes mostly related to cell cycle, such as cell proliferation, growth, differentiation, etc. Through the Pfam classification, we found that miRNAs belonging to the same family tend to have targets from the same family which displays the synergistic function of these miRNAs. Finally, the case study on miR-519d and miR-21-regulated sub-network was performed to support our findings. PMID:27694936

  8. SuperAGILE and Gamma Ray Bursts

    SciTech Connect

    Pacciani, Luigi; Costa, Enrico; Del Monte, Ettore; Donnarumma, Immacolata; Evangelista, Yuri; Feroci, Marco; Frutti, Massimo; Lazzarotto, Francesco; Lapshov, Igor; Rubini, Alda; Soffitta, Paolo; Tavani, Marco; Barbiellini, Guido; Mastropietro, Marcello; Morelli, Ennio; Rapisarda, Massimo

    2006-05-19

    The solid-state hard X-ray imager of AGILE gamma-ray mission -- SuperAGILE -- has a six arcmin on-axis angular resolution in the 15-45 keV range, a field of view in excess of 1 steradian. The instrument is very light: 5 kg only. It is equipped with an on-board self triggering logic, image deconvolution, and it is able to transmit the coordinates of a GRB to the ground in real-time through the ORBCOMM constellation of satellites. Photon by photon Scientific Data are sent to the Malindi ground station at every contact. In this paper we review the performance of the SuperAGILE experiment (scheduled for a launch in the middle of 2006), after its first onground calibrations, and show the perspectives for Gamma Ray Bursts.

  9. An investigation of fighter aircraft agility

    NASA Technical Reports Server (NTRS)

    Valasek, John; Downing, David R.

    1993-01-01

    This report attempts to unify in a single document the results of a series of studies on fighter aircraft agility funded by the NASA Ames Research Center, Dryden Flight Research Facility and conducted at the University of Kansas Flight Research Laboratory during the period January 1989 through December 1993. New metrics proposed by pilots and the research community to assess fighter aircraft agility are collected and analyzed. The report develops a framework for understanding the context into which the various proposed fighter agility metrics fit in terms of application and testing. Since new metrics continue to be proposed, this report does not claim to contain every proposed fighter agility metric. Flight test procedures, test constraints, and related criteria are developed. Instrumentation required to quantify agility via flight test is considered, as is the sensitivity of the candidate metrics to deviations from nominal pilot command inputs, which is studied in detail. Instead of supplying specific, detailed conclusions about the relevance or utility of one candidate metric versus another, the authors have attempted to provide sufficient data and analyses for readers to formulate their own conclusions. Readers are therefore ultimately responsible for judging exactly which metrics are 'best' for their particular needs. Additionally, it is not the intent of the authors to suggest combat tactics or other actual operational uses of the results and data in this report. This has been left up to the user community. Twenty of the candidate agility metrics were selected for evaluation with high fidelity, nonlinear, non real-time flight simulation computer programs of the F-5A Freedom Fighter, F-16A Fighting Falcon, F-18A Hornet, and X-29A. The information and data presented on the 20 candidate metrics which were evaluated will assist interested readers in conducting their own extensive investigations. The report provides a definition and analysis of each metric; details

  10. The Influence of Agility Training on Physiological and Cognitive Performance

    DTIC Science & Technology

    2010-11-01

    training, subjects completed a physical and cognitive battery of serum cortisol, VO2max, vertical jump , reaction time, Illinois Agility Test , body...strong trends toward the agility group improving more than the traditional group on VO2max (p=0.12), vertical jump (p=0.06), Illinois Agility Test ...levels, maximal oxygen uptake, Illinois Agility Test , Makoto reaction time, and vertical jump . The cognitive portion of the testing sessions

  11. MicroRNA Profile of Lung Tumor Tissues Is Associated with a High Risk Plasma miRNA Signature

    PubMed Central

    Fortunato, Orazio; Verri, Carla; Pastorino, Ugo; Sozzi, Gabriella; Boeri, Mattia

    2016-01-01

    Lung cancer is the most common cause of cancer deaths worldwide. MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression. Many studies have reported that alterations in miRNA expression are involved in several human tumors. We have previously identified a circulating miRNA signature classifier (MSC) able to discriminate lung cancer with more aggressive features. In the present work, microarray miRNA profiling of tumor tissues collected from 19 lung cancer patients with an available MSC result were perform in order to find a possible association between miRNA expression and the MSC risk level. Eleven tissue mature miRNAs and six miRNA precursors were observed to be associated with the plasma MSC risk level of patients. Not one of these miRNAs was included in the MSC algorithm. A pathway enrichment analysis revealed a role of these miRNA in the main pathways determining lung cancer aggressiveness. Overall, these findings add to the knowledge that tissue and plasma miRNAs behave as excellent diagnostic and prognostic biomarkers, which may find rapid application in clinical settings. PMID:27600084

  12. Theoretical aspects of the agile mirror

    NASA Astrophysics Data System (ADS)

    Manheimer, Wallace M.; Fernsler, Richard

    1994-01-01

    A planar plasma mirror which can be oriented electronically could have the capability of providing electronic steering of a microwave beam in a radar or electronic warfare system. This system is denoted the agile mirror. A recent experiment has demonstrated such a planar plasma and the associated microwave reflection. This plasma was produced by a hollow cathode glow discharge, where the hollow cathode was a grooved metallic trench in a Lucite plate. Various theoretical aspects of this configuration of an agile mirror are examined here.

  13. Regulation of human chondrocyte function through direct inhibition of cartilage master regulator SOX9 by microRNA-145 (miRNA-145).

    PubMed

    Martinez-Sanchez, Aida; Dudek, Katarzyna A; Murphy, Chris L

    2012-01-06

    Articular cartilage enables weight bearing and near friction-free movement in the joints. Critical to its function is the production of a specialized, mechanocompetent extracellular matrix controlled by master regulator transcription factor SOX9. Mutations in SOX9 cause campomelic dysplasia, a haploinsufficiency disorder resulting in severe skeletal defects and dwarfism. Although much is understood about how SOX9 regulates cartilage matrix synthesis and hence joint function, how this master regulator is itself regulated remains largely unknown. Here we identify a specific microRNA, miR-145, as a direct regulator of SOX9 in normal healthy human articular chondrocytes. We show that miR-145 directly represses SOX9 expression in human cells through a unique binding site in its 3'-UTR not conserved in mice. Modulation of miR-145 induced profound changes in the human chondrocyte phenotype. Specifically, increased miR-145 levels cause greatly reduced expression of critical cartilage extracellular matrix genes (COL2A1 and aggrecan) and tissue-specific microRNAs (miR-675 and miR-140) and increased levels of the hypertrophic markers RUNX2 and MMP13, characteristic of changes occurring in osteoarthritis. We propose miR-145 as an important regulator of human chondrocyte function and a new target for cartilage repair.

  14. Columbia University: Computational Human High-grade Glioblastoma Multiforme Interactome - miRNA (Post-transcriptional) Layer | Office of Cancer Genomics

    Cancer.gov

    The Human High-Grade Glioma Interactome (HGi) contains a genome-wide complement of molecular interactions that are Glioblastoma Multiforme (GBM)-specific. HGi v3 contains the post-transcriptional layer of the HGi, which includes the miRNA-target (RNA-RNA) layer of the interactome. Read the Abstract

  15. miRNA gene counts in chromosomes vary widely in a species and biogenesis of miRNA largely depends on transcription or post-transcriptional processing of coding genes

    PubMed Central

    Ghorai, Atanu; Ghosh, Utpal

    2014-01-01

    MicroRNAs target specific mRNA(s) to silence its expression and thereby regulate various cellular processes. We have investigated miRNA gene counts in chromosomes for 20 different species and observed wide variation. Certain chromosomes have extremely high number of miRNA gene compared with others in all the species. For example, high number of miRNA gene in X chromosome and the least or absence of miRNA gene in Y chromosome was observed in all species. To search the criteria governing such variation of miRNA gene counts in chromosomes, we have selected three parameters- length, number of non-coding and coding genes in a chromosome. We have calculated Pearson's correlation coefficient of miRNA gene counts with length, number of non-coding and coding genes in a chromosome for all 20 species. Major number of species showed that number of miRNA gene was not correlated with chromosome length. Eighty five percent of species under study showed strong positive correlation coefficient (r ≥ 0.5) between the numbers of miRNA gene vs. non-coding gene in chromosomes as expected because miRNA is a sub-set of non-coding genes. 55% species under study showed strong positive correlation coefficient (r ≥ 0.5) between numbers of miRNA gene vs. coding gene. We hypothesize biogenesis of miRNA largely depends on coding genes, an evolutionary conserved process. Chromosomes having higher number of miRNA genes will be most likely playing regulatory roles in several cellular processes including different disorders. In humans, cancer and cardiovascular disease associated miRNAs are mostly intergenic and located in Chromosome 19, X, 14, and 1. PMID:24808907

  16. Planning, Estimating, and Monitoring Progress in Agile Systems Development Environments

    DTIC Science & Technology

    2010-04-01

    Jilemanifesto.orgf Nt:JRJ’HRDP GRUMMAN Agile Terminology Term Definition P d B kl R i /U S i b l dro uct ac og equ rements ser tor es to e comp ete Iteration...Marion, McKelvey, & Uhl- Bien . (2007). Leadership Quarterly, 18(4), 298-318. Agile Development Practices Agile Project Management with Scrum Ken Schwaber

  17. A knowledge base for the discovery of function, diagnostic potential and drug effects on cellular and extracellular miRNAs

    PubMed Central

    2014-01-01

    Background MicroRNAs (miRNAs) are small noncoding RNAs that play an important role in the regulation of various biological processes through their interaction with cellular mRNAs. A significant amount of miRNAs has been found in extracellular human body fluids (e.g. plasma and serum) and some circulating miRNAs in the blood have been successfully revealed as biomarkers for diseases including cardiovascular diseases and cancer. Released miRNAs do not necessarily reflect the abundance of miRNAs in the cell of origin. It is claimed that release of miRNAs from cells into blood and ductal fluids is selective and that the selection of released miRNAs may correlate with malignancy. Moreover, miRNAs play a significant role in pharmacogenomics by down-regulating genes that are important for drug function. In particular, the use of drugs should be taken into consideration while analyzing plasma miRNA levels as drug treatment. This may impair their employment as biomarkers. Description We enriched our manually curated extracellular/circulating microRNAs database, miRandola, by providing (i) a systematic comparison of expression profiles of cellular and extracellular miRNAs, (ii) a miRNA targets enrichment analysis procedure, (iii) information on drugs and their effect on miRNA expression, obtained by applying a natural language processing algorithm to abstracts obtained from PubMed. Conclusions This allows users to improve the knowledge about the function, diagnostic potential, and the drug effects on cellular and circulating miRNAs. PMID:25077952

  18. Inference of miRNA targets using evolutionary conservation and pathway analysis

    PubMed Central

    Gaidatzis, Dimos; van Nimwegen, Erik; Hausser, Jean; Zavolan, Mihaela

    2007-01-01

    Background MicroRNAs have emerged as important regulatory genes in a variety of cellular processes and, in recent years, hundreds of such genes have been discovered in animals. In contrast, functional annotations are available only for a very small fraction of these miRNAs, and even in these cases only partially. Results We developed a general Bayesian method for the inference of miRNA target sites, in which, for each miRNA, we explicitly model the evolution of orthologous target sites in a set of related species. Using this method we predict target sites for all known miRNAs in flies, worms, fish, and mammals. By comparing our predictions in fly with a reference set of experimentally tested miRNA-mRNA interactions we show that our general method performs at least as well as the most accurate methods available to date, including ones specifically tailored for target prediction in fly. An important novel feature of our model is that it explicitly infers the phylogenetic distribution of functional target sites, independently for each miRNA. This allows us to infer species-specific and clade-specific miRNA targeting. We also show that, in long human 3' UTRs, miRNA target sites occur preferentially near the start and near the end of the 3' UTR. To characterize miRNA function beyond the predicted lists of targets we further present a method to infer significant associations between the sets of targets predicted for individual miRNAs and specific biochemical pathways, in particular those of the KEGG pathway database. We show that this approach retrieves several known functional miRNA-mRNA associations, and predicts novel functions for known miRNAs in cell growth and in development. Conclusion We have presented a Bayesian target prediction algorithm without any tunable parameters, that can be applied to sequences from any clade of species. The algorithm automatically infers the phylogenetic distribution of functional sites for each miRNA, and assigns a posterior

  19. Application of miRNAs as Biomarkers of Exposure and Effects ...

    EPA Pesticide Factsheets

    Of the known epigenetic mechanisms, non-coding RNA and more specifically, microRNA (miRNA), offer the most immediate promise for risk assessment applications because these molecules can serve as excellent biomarkers of toxicity. The advantages of miRNA versus more classical protein toxicity biomarkers include: greater stability and earlier appearance in biofluids that can be obtained by relatively non-invasive approaches; tissue- and/or cell-specific expression patterns; evolutionary conservation in both sequence and function across species; and novel technologies for sensitive and accurate quantification. Further, information on individual miRNA is readily available through databases such as miRBase and others. Thus miRNA biomarkers offer substantial benefits in terms of cost, time, convenience, sensitivity, and specificity when assessing environmental-induced toxicity in model systems or human cohorts. Although this field is rapidly expanding, documented examples include associations of miR-155 with lymphocytic leukemia, miR-122 with liver toxicity; miR-206 with skeletal muscle disease; and miR-208a-3p with cardiac toxicity. Despite their promise, some challenges in using miRNAs as toxicity biomarkers remain, including the need for improved methods for normalizing miRNA measurements, translating findings of biofluid-based miRNA biomarker alterations in experimental models to human health and specific cell/tissue injury, and finally, the need to better defi

  20. Biogenesis and regulation of the let-7 miRNAs and their functional implications.

    PubMed

    Lee, Hosuk; Han, Sungwook; Kwon, Chang Seob; Lee, Daeyoup

    2016-02-01

    The let-7 miRNA was one of the first miRNAs discovered in the nematode, Caenorhabditis elegans, and its biological functions show a high level of evolutionary conservation from the nematode to the human. Unlike in C. elegans, higher animals have multiple isoforms of let-7 miRNAs; these isoforms share a consensus sequence called the 'seed sequence' and these isoforms are categorized into let-7 miRNA family. The expression of let-7 family is required for developmental timing and tumor suppressor function, but must be suppressed for the self-renewal of stem cells. Therefore, let-7 miRNA biogenesis must be carefully controlled. To generate a let-7 miRNA, a primary transcript is produced by RNA polymerase II and then subsequently processed by Drosha/DGCR8, TUTase, and Dicer. Because dysregulation of let-7 processing is deleterious, biogenesis of let-7 is tightly regulated by cellular factors, such as the RNA binding proteins, LIN28A/B and DIS3L2. In this review, we discuss the biological functions and biogenesis of let-7 miRNAs, focusing on the molecular mechanisms of regulation of let-7 biogenesis in vertebrates, such as the mouse and the human.

  1. Psmir: a database of potential associations between small molecules and miRNAs

    PubMed Central

    Meng, Fanlin; Wang, Jing; Dai, Enyu; Yang, Feng; Chen, Xiaowen; Wang, Shuyuan; Yu, Xuexin; Liu, Dianming; Jiang, Wei

    2016-01-01

    miRNAs are key post-transcriptional regulators of many essential biological processes, and their dysregulation has been validated in almost all human cancers. Restoring aberrantly expressed miRNAs might be a novel therapeutics. Recently, many studies have demonstrated that small molecular compounds can affect miRNA expression. Thus, prediction of associations between small molecules and miRNAs is important for investigation of miRNA-targeted drugs. Here, we analyzed 39 miRNA-perturbed gene expression profiles, and then calculated the similarity of transcription responses between miRNA perturbation and drug treatment to predict drug-miRNA associations. At the significance level of 0.05, we obtained 6501 candidate associations between 1295 small molecules and 25 miRNAs, which included 624 FDA approved drugs. Finally, we constructed the Psmir database to store all potential associations and the related materials. In a word, Psmir served as a valuable resource for dissecting the biological significance in small molecules’ effects on miRNA expression, which will facilitate developing novel potential therapeutic targets or treatments for human cancers. Psmir is supported by all major browsers, and is freely available at http://www.bio-bigdata.com/Psmir/. PMID:26759061

  2. Psmir: a database of potential associations between small molecules and miRNAs.

    PubMed

    Meng, Fanlin; Wang, Jing; Dai, Enyu; Yang, Feng; Chen, Xiaowen; Wang, Shuyuan; Yu, Xuexin; Liu, Dianming; Jiang, Wei

    2016-01-13

    miRNAs are key post-transcriptional regulators of many essential biological processes, and their dysregulation has been validated in almost all human cancers. Restoring aberrantly expressed miRNAs might be a novel therapeutics. Recently, many studies have demonstrated that small molecular compounds can affect miRNA expression. Thus, prediction of associations between small molecules and miRNAs is important for investigation of miRNA-targeted drugs. Here, we analyzed 39 miRNA-perturbed gene expression profiles, and then calculated the similarity of transcription responses between miRNA perturbation and drug treatment to predict drug-miRNA associations. At the significance level of 0.05, we obtained 6501 candidate associations between 1295 small molecules and 25 miRNAs, which included 624 FDA approved drugs. Finally, we constructed the Psmir database to store all potential associations and the related materials. In a word, Psmir served as a valuable resource for dissecting the biological significance in small molecules' effects on miRNA expression, which will facilitate developing novel potential therapeutic targets or treatments for human cancers. Psmir is supported by all major browsers, and is freely available at http://www.bio-bigdata.com/Psmir/.

  3. Caenorhabditis elegans period homolog lin-42 regulates the timing of heterochronic miRNA expression.

    PubMed

    McCulloch, Katherine A; Rougvie, Ann E

    2014-10-28

    MicroRNAs (miRNAs) are small RNAs that regulate gene expression posttranscriptionally via the 3' UTR of target mRNAs and were first identified in the Caenorhabditis elegans heterochronic pathway. miRNAs have since been found in many organisms and have broad functions, including control of differentiation and pluripotency in humans. lin-4 and let-7-family miRNAs regulate developmental timing in C. elegans, and their proper temporal expression ensures cell lineage patterns are correctly timed and sequentially executed. Although much is known about miRNA biogenesis, less is understood about how miRNA expression is timed and regulated. lin-42, the worm homolog of the circadian rhythm gene period of flies and mammals, is another core component of the heterochronic gene pathway. lin-42 mutants have a precocious phenotype, in which later-stage programs are executed too early, but the placement of lin-42 in the timing pathway is unclear. Here, we demonstrate that lin-42 negatively regulates heterochronic miRNA transcription. let-7 and the related miRNA miR-48 accumulate precociously in lin-42 mutants. This defect reflects transcriptional misregulation because enhanced expression of both primary miRNA transcripts (pri-miRNAs) and a let-7 promoter::gfp fusion are observed. The pri-miRNA levels oscillate during larval development, in a pattern reminiscent of lin-42 expression. Importantly, we show that lin-42 is not required for this cycling; instead, peak amplitude is increased. Genetic analyses further confirm that lin-42 acts through let-7 family miRNAs. Taken together, these data show that a key function of lin-42 in developmental timing is to dampen pri-miRNAs levels, preventing their premature expression as mature miRNAs.

  4. Assessing sample and miRNA profile quality in serum and plasma or other biofluids.

    PubMed

    Blondal, Thorarinn; Jensby Nielsen, Søren; Baker, Adam; Andreasen, Ditte; Mouritzen, Peter; Wrang Teilum, Maria; Dahlsveen, Ina K

    2013-01-01

    MicroRNAs (miRNAs) constitute a class of small cellular RNAs (typically 21-23nt) that function as post-transcriptional regulators of gene expression. Current estimates indicate that more than one third of the cellular transcriptome is regulated by miRNAs, although they are relatively few in number (less than 2000 human miRNAs). The high relative stability of miRNA in common clinical tissues and biofluids (e.g. plasma, serum, urine, saliva, etc.) and the ability of miRNA expression profiles to accurately classify discrete tissue types and disease states have positioned miRNA quantification as a promising new tool for a wide range of diagnostic applications. Furthermore miRNAs have been shown to be rapidly released from tissues into the circulation with the development of pathology. To facilitate discovery and clinical development of miRNA-based biomarkers, we developed a genome-wide Locked Nucleic Acid (LNA™)-based miRNA qPCR platform with unparalleled sensitivity and robustness. The platform allows high-throughput profiling of miRNAs from important clinical sources without the need for pre-amplification. Using this system, we have profiled thousands of biofluid samples including blood derived plasma and serum. An extensive quality control (QC) system has been implemented in order to secure technical excellence and reveal any unwanted bias coming from pre-analytical or analytical variables. We present our approaches to sample and RNA QC as well as data QC and normalization. Specifically we have developed normal reference ranges for circulating miRNAs in serum and plasma as well as a hemolysis indicator based on microRNA expression.

  5. miRNA-10b sponge: An anti-breast cancer study in vitro

    PubMed Central

    LIANG, AI-LING; ZHANG, TING-TING; ZHOU, NING; WU, CUI YUN; LIN, MAN-HUA; LIU, YONG-JUN

    2016-01-01

    Breast cancer is a malignant tumor with the highest incidence among women. Breast cancer metastasis is the major cause of treatment failure and mortality among such patients. MicroRNAs (miRNAs) are a class of small molecular non-coding regulatory RNAs, which act as oncogenes or tumor suppressors in breast cancer. miRNA-10b has been found to exhibit a high expression level in advanced and metastatic breast cancer, and is closely related to breast cancer metastasis. An miRNA sponge is an mRNA with several repeated sequences of complete or incomplete complementarity to the natural miRNA in its 3′ non-translating region. It acts as a sponge adsorbing miRNAs and ensures their separation from their targets and inhibits their function. The present study designed a sponge plasmid against miRNA-10b and transiently transfected it into high and low metastatic human breast cancer cell lines MDA-MB-231 and MCF-7, and analyzed the effects of the miRNA-10b sponge on the growth and proliferation, migration and invasion in these cell lines. qRT-PCR results found that the sponge plasmid effectively inhibited the expression of miRNA-10b, and upregulated the expression of the miRNA-10b target protein HOXD-10. The results from the CCK-8 assay found that the miRNA-10b sponge inhibited the growth of breast cancer cell lines MDA-MB-231 and MCF-7. Results of the plate cloning experiments indicated that the miRNA-10b sponge suppressed the colony formation of the MDA-MB-231 and MCF-7 cells. The results of wound healing and Transwell assays showed that the miRNA-10b sponge inhibited the migration and invasion of the breast cancer cell lines MDA-MB-231 and MCF-7. Our results demonstrated that the miRNA-10b sponge effectively inhibited the growth and proliferation of breast cancer MDA-MB-231 and MCF-7 cells. In addition, it also restrained the migration and invasion of human highly metastatic breast cancer MDA-MB-231 cells. PMID:26820121

  6. On-the-fly selection of cell-specific enhancers, genes, miRNAs and proteins across the human body using SlideBase

    PubMed Central

    Ienasescu, Hans; Li, Kang; Andersson, Robin; Vitezic, Morana; Rennie, Sarah; Chen, Yun; Vitting-Seerup, Kristoffer; Lagoni, Emil; Boyd, Mette; Bornholdt, Jette; de Hoon, Michiel J. L.; Kawaji, Hideya; Lassmann, Timo; Hayashizaki, Yoshihide; Forrest, Alistair R. R.; Carninci, Piero; Sandelin, Albin

    2016-01-01

    Genomics consortia have produced large datasets profiling the expression of genes, micro-RNAs, enhancers and more across human tissues or cells. There is a need for intuitive tools to select subsets of such data that is the most relevant for specific studies. To this end, we present SlideBase, a web tool which offers a new way of selecting genes, promoters, enhancers and microRNAs that are preferentially expressed/used in a specified set of cells/tissues, based on the use of interactive sliders. With the help of sliders, SlideBase enables users to define custom expression thresholds for individual cell types/tissues, producing sets of genes, enhancers etc. which satisfy these constraints. Changes in slider settings result in simultaneous changes in the selected sets, updated in real time. SlideBase is linked to major databases from genomics consortia, including FANTOM, GTEx, The Human Protein Atlas and BioGPS. Database URL: http://slidebase.binf.ku.dk PMID:28025337

  7. On-the-fly selection of cell-specific enhancers, genes, miRNAs and proteins across the human body using SlideBase.

    PubMed

    Ienasescu, Hans; Li, Kang; Andersson, Robin; Vitezic, Morana; Rennie, Sarah; Chen, Yun; Vitting-Seerup, Kristoffer; Lagoni, Emil; Boyd, Mette; Bornholdt, Jette; de Hoon, Michiel J L; Kawaji, Hideya; Lassmann, Timo; Hayashizaki, Yoshihide; Forrest, Alistair R R; Carninci, Piero; Sandelin, Albin

    2016-01-01

    Genomics consortia have produced large datasets profiling the expression of genes, micro-RNAs, enhancers and more across human tissues or cells. There is a need for intuitive tools to select subsets of such data that is the most relevant for specific studies. To this end, we present SlideBase, a web tool which offers a new way of selecting genes, promoters, enhancers and microRNAs that are preferentially expressed/used in a specified set of cells/tissues, based on the use of interactive sliders. With the help of sliders, SlideBase enables users to define custom expression thresholds for individual cell types/tissues, producing sets of genes, enhancers etc. which satisfy these constraints. Changes in slider settings result in simultaneous changes in the selected sets, updated in real time. SlideBase is linked to major databases from genomics consortia, including FANTOM, GTEx, The Human Protein Atlas and BioGPS.Database URL: http://slidebase.binf.ku.dk.

  8. Lean and Agile: An Epistemological Reflection

    ERIC Educational Resources Information Center

    Browaeys, Marie-Joelle; Fisser, Sandra

    2012-01-01

    Purpose: The aim of the paper is to contribute to the discussion of treating the concepts of lean and agile in isolation or combination by presenting an alternative view from complexity thinking on these concepts, considering an epistemological approach to this topic. Design/methodology/approach: The paper adopts an epistemological approach, using…

  9. Achieving agility through parameter space qualification

    SciTech Connect

    Diegert, K.V.; Easterling, R.G.; Ashby, M.R.; Benavides, G.L.; Forsythe, C.; Jones, R.E.; Longcope, D.B.; Parratt, S.W.

    1995-02-01

    The A-primed (Agile Product Realization of Innovative electro-Mechanical Devices) project is defining and proving processes for agile product realization for the Department of Energy complex. Like other agile production efforts reported in the literature, A-primed uses concurrent engineering and information automation technologies to enhance information transfer. A unique aspect of our approach to agility is the qualification during development of a family of related product designs and their production processes, rather than a single design and its attendant processes. Applying engineering principles and statistical design of experiments, economies of test and analytic effort are realized for the qualification of the device family as a whole. Thus the need is minimized for test and analysis to qualify future devices from this family, thereby further reducing the design-to-production cycle time. As a measure of the success of the A-primed approach, the first design took 24 days to produce, and operated correctly on the first attempt. A flow diagram for the qualification process is presented. Guidelines are given for implementation, based on the authors experiences as members of the A-primed qualification team.

  10. The Holy Grail of Agile Acquisition

    DTIC Science & Technology

    2010-04-01

    Bestsellers …” [Erwin 2009] Motivation • Despite of Erwin’s recommendation… – Agility seems to be a simple concept and it is commonly perceived as a virtue...osd mil/dapaproject/>. . . Erwin 2009 Erwin, S.I., Washington Pulse, Pentagon Brass: Stay Away From Management Bestsellers , National Defense, August

  11. AGILE and Gamma-Ray Bursts

    SciTech Connect

    Longo, Francesco; Tavani, M.; Barbiellini, G.; Argan, A.; Basset, M.; Boffelli, F.; Bulgarelli, A.; Caraveo, P.; Cattaneo, P.; Chen, A.; Costa, E.; Del Monte, E.; Di Cocco, G.; Di Persio, G.; Donnarumma, I.; Feroci, M.; Fiorini, M.; Foggetta, L.; Froysland, T.; Frutti, M.

    2006-05-19

    AGILE is a Scientific Mission dedicated to high-energy astrophysics supported by ASI with scientific participation of INAF and INFN. The AGILE instrument is designed to simultaneously detect and image photons in the 30 MeV - 50 GeV and 15 - 45 keV energy bands with excellent imaging and timing capabilities, and a large field of view covering {approx} 1/5 of the entire sky at energies above 30 MeV. A CsI calorimeter is capable of GRB triggering in the energy band 0.3-50 MeV. The broadband detection of GRBs and the study of implications for particle acceleration and high energy emission are primary goals of th emission. AGILE can image GRBs with 2-3 arcminutes error boxes in the hard X-ray range, and provide broadband photon-by photon detection in the 15-45 keV, 03-50 MeV, and 30 MeV-30 GeV energy ranges. Microsecond on-board photon tagging and a {approx} 100 microsecond gamma-ray detection deadtime will be crucial for fast GRB timing. On-board calculated GRB coordinates and energy fluxes will be quickly transmitted to the ground by an ORBCOMM transceiver. AGILE have recently (December 2005) completed its gamma-ray calibration. It is now (January 2006) undergoing satellite integration and testing. The PLSV launch is planned in early 2006. AGILE is then foreseen to be fully operational during the summer of 2006. It will be the only mission entirely dedicated to high-energy astrophysics above 30 MeV during the period mid-2006/mid-2007.

  12. Investigating the strategic antecedents of agility in humanitarian logistics.

    PubMed

    L'Hermitte, Cécile; Brooks, Benjamin; Bowles, Marcus; Tatham, Peter H

    2016-12-16

    This study investigates the strategic antecedents of operational agility in humanitarian logistics. It began by identifying the particular actions to be taken at the strategic level of a humanitarian organisation to support field-level agility. Next, quantitative data (n=59) were collected on four strategic-level capabilities (being purposeful, action-focused, collaborative, and learning-oriented) and on operational agility (field responsiveness and flexibility). Using a quantitative analysis, the study tested the relationship between organisational capacity building and operational agility and found that the four strategic-level capabilities are fundamental building blocks of agility. Collectively they account for 52 per cent of the ability of humanitarian logisticians to deal with ongoing changes and disruptions in the field. This study emphasises the need for researchers and practitioners to embrace a broader perspective of agility in humanitarian logistics. In addition, it highlights the inherently strategic nature of agility, the development of which involves focusing simultaneously on multiple drivers.

  13. Development of a circulating miRNA assay to monitor tumor burden: From mouse to man.

    PubMed

    Greystoke, Alastair; Ayub, Mahmood; Rothwell, Dominic G; Morris, Dan; Burt, Deborah; Hodgkinson, Cassandra L; Morrow, Christopher J; Smith, Nigel; Aung, Kyaw; Valle, Juan; Carter, Louise; Blackhall, Fiona; Dive, Caroline; Brady, Ged

    2016-02-01

    Circulating miRNA stability suggests potential utility of miRNA based biomarkers to monitor tumor burden and/or progression, particularly in cancer types where serial biopsy is impractical. Assessment of miRNA specificity and sensitivity is challenging within the clinical setting. To address this, circulating miRNAs were examined in mice bearing human SCLC tumor xenografts and SCLC patient derived circulating tumor cell explant models (CDX). We identified 49 miRNAs using human TaqMan Low Density Arrays readily detectable in 10 μl tail vein plasma from mice carrying H526 SCLC xenografts that were low or undetectable in non-tumor bearing controls. Circulating miR-95 measured serially in mice bearing CDX was detected with tumor volumes as low as 10 mm(3) and faithfully reported subsequent tumor growth. Having established assay sensitivity in mouse models, we identified 26 miRNAs that were elevated in a stage dependent manner in a pilot study of plasma from SCLC patients (n = 16) compared to healthy controls (n = 11) that were also elevated in the mouse models. We selected a smaller panel of 10 previously reported miRNAs (miRs 95, 141, 200a, 200b, 200c, 210, 335#, 375, 429) that were consistently elevated in SCLC, some of which are reported to be elevated in other cancer types. Using a multiplex qPCR assay, elevated levels of miRNAs across the panel were also observed in a further 66 patients with non-small cell lung, colorectal or pancreatic cancers. The utility of this circulating miRNA panel as an early warning of tumor progression across several tumor types merits further evaluation in larger studies.

  14. MiRNA-27a promotes the proliferation and invasion of human gastric cancer MGC803 cells by targeting SFRP1 via Wnt/β-catenin signaling pathway

    PubMed Central

    Wu, Fang; Li, Jun; Guo, Ni; Wang, Xiao-Hui; Liao, Yu-Qian

    2017-01-01

    This study aims to elucidate the effects of microRNA-27a (miR-27a) on the proliferation and invasion of gastric cancer (GC) cells by targeting SFRP1 via Wnt/β-catenin signaling pathway. GC and normal adjacent tissues were collected from 273 GC patients. Human gastric cancer cell line (MGC803) and normal human gastric mucosal cell line (GES-1) were cultured. The miR-27a mRNA expression was analyzed using Quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) test was used to detect miR-27a and SFRP1 protein expressions. After transfection, cells were divided into five groups: the negative control (NC) group, the miR-27a inhibitor group, the miR-27a mimics group, the miR-27a inhibitor + SFRP1 siRNA group and the miR-27a mimics + SFRP1 overexpression group. Western blotting was conducted to test SFRP1 and Wnt/β-catenin protein expression. Analysis for the target gene of miR-27a was performed using Luciferase assay. Cell proliferation, migration and invasion were determined by CCK8 and Transwell assay. The dual-luciferase reporter assay system was applied to analyze the effects of miR-27a on Wnt/β-catenin signaling pathway. In GC tissue and cell line, miR-27a protein and mRNA expressions were up-regulated, and SFRP1 protein and mRNA expressions were down-regulated. Luciferase assay indicated that miR-27a might target SFRP1 and regulate its expressions. When miR-27a was down-regulated, SFRP1 was up-regulated, and β-catenin, Wnt, p-β-catenin, and p-Wnt were significantly down-regulated. Compared with the NC group, the proliferation, migration and invasion of GC cells were remarkably increased in the miR-27a group, but these were declined in the miR-27a mimics + SFRP1 overexpression group. The proliferation, migration and invasion of GC cells were elevated in the miR-27a inhibitor + SFRP1 siRNA group compared with the miR-27a inhibitor group. These results showed that miR-27a was highly expressed in GC tissues and cells, and it might

  15. The Emerging Role of miRNAs in HTLV-1 Infection and ATLL Pathogenesis

    PubMed Central

    Moles, Ramona; Nicot, Christophe

    2015-01-01

    Human T-cell leukemia virus (HTLV)-1 is a human retrovirus and the etiological agent of adult T-cell leukemia/lymphoma (ATLL), a fatal malignancy of CD4/CD25+ T lymphocytes. In recent years, cellular as well as virus-encoded microRNA (miRNA) have been shown to deregulate signaling pathways to favor virus life cycle. HTLV-1 does not encode miRNA, but several studies have demonstrated that cellular miRNA expression is affected in infected cells. Distinct mechanisms such as transcriptional, epigenetic or interference with miRNA processing machinery have been involved. This article reviews the current knowledge of the role of cellular microRNAs in virus infection, replication, immune escape and pathogenesis of HTLV-1. PMID:26205403

  16. miRNA-141 attenuates UV-induced oxidative stress via activating Keap1-Nrf2 signaling in human retinal pigment epithelium cells and retinal ganglion cells.

    PubMed

    Cheng, Li-Bo; Li, Ke-Ran; Yi, Nan; Li, Xiu-Miao; Wang, Feng; Xue, Bo; Pan, Ying-Shun; Yao, Jin; Jiang, Qin; Wu, Zhi-Feng

    2017-01-04

    Activation of NF-E2-related factor 2 (Nrf2) signaling could protect cells from ultra violet (UV) radiation. We aim to provoke Nrf2 activation via downregulating its inhibitor Keap1 by microRNA-141 ("miR-141"). In both human retinal pigment epithelium cells (RPEs) and retinal ganglion cells (RGCs), forced-expression of miR-141 downregulated Keap1, causing Nrf2 stabilization, accumulation and nuclear translocation, which led to transcription of multiple antioxidant-responsive element (ARE) genes (HO1, NOQ1 and GCLC). Further, UV-induced reactive oxygen species (ROS) production and cell death were significantly attenuated in miR-141-expressing RPEs and RGCs. On the other hand, depletion of miR-141 via expressing its inhibitor antagomiR-141 led to Keap1 upregulation and Nrf2 degradation, which aggravated UV-induced death of RPEs and RGCs. Significantly, Nrf2 shRNA knockdown almost abolished miR-141-mediated cytoprotection against UV in RPEs. These results demonstrate that miR-141 targets Keap1 to activate Nrf2 signaling, which protects RPEs and RGCs from UV radiation.

  17. MiRNAs in bone diseases.

    PubMed

    Moore, Benjamin T; Xiao, Peng

    2013-01-01

    MicroRNAs (miRNAs), which mainly inhibit protein expression by targeting the 3'UTR (untranslated region) of mRNAs, are known to play various roles in the pathogenesis of many different types of diseases. Specifically, in bone diseases, recent emphasis has been placed on the involvement of miRNAs in the differentiation and proliferation of bone and cartilage cells, particularly with regards to how these mechanisms contribute to bone homeostasis. In this review, we summarize miRNAs that are important in the differentiation and proliferation of bone cells, and specific miRNAs associated with bone diseases, such as osteoporosis, osteoarthritis and rheumatoid arthritis. This review also provides the perspective that miRNA studies will identify not only new mechanisms in basic bone research, but also potential novel diagnostic biomarkers and drug targets for bone diseases.

  18. Loss of miRNAs during processing and storage of cow's (Bos taurus) milk.

    PubMed

    Howard, Katherine M; Jati Kusuma, Rio; Baier, Scott R; Friemel, Taylor; Markham, Laura; Vanamala, Jairam; Zempleni, Janos

    2015-01-21

    MicroRNAs (miRs, miRNAs) play central roles in gene regulation. Previously, we reported that miRNAs from pasteurized, store-bought bovine milk have biological activity in humans. Here, we assessed the effects of milk processing, storage, somatic cell content, and handling by consumers on the degradation of miRNAs in milk; we also quantified miRNAs in dairy products. Pasteurization and homogenization caused a 63% loss of miR-200c, whereas a 67% loss observed for miR-29b was statistically significant only in skim milk. Effects of cold storage and somatic cell content were quantitatively minor (<2% loss). Heating in the microwave caused a 40% loss of miR-29b but no loss of miR-200c. The milk fat content had no effect on miRNA stability during storage and microwave heating. The concentrations of miRNAs in dairy products were considerably lower than in store-bought milk. We conclude that processing of milk by dairies and handling by consumers causes a significant loss of miRNAs.

  19. Expression of miRNAs in ovine fetal gonads: potential role in gonadal differentiation

    PubMed Central

    2011-01-01

    Background Gonadal differentiation in the mammalian fetus involves a complex dose-dependent genetic network. Initiation and progression of fetal ovarian and testicular pathways are accompanied by dynamic expression patterns of thousands of genes. We postulate these expression patterns are regulated by small non-coding RNAs called microRNAs (miRNAs). The aim of this study was to identify the expression of miRNAs in mammalian fetal gonads using sheep as a model. Methods We determined the expression of 128 miRNAs by real time PCR in early-gestational (gestational day (GD) 42) and mid-gestational (GD75) sheep ovaries and testes. Expression data were further examined and validated by bioinformatic analysis. Results Expression analysis revealed significant differences between ovaries and testes among 24 miRNAs at GD42, and 43 miRNAs at GD75. Bioinformatic analysis revealed that a number of differentially expressed miRNAs are predicted to target genes known to be important in mammalian gonadal development, including ESR1, CYP19A1, and SOX9. In situ hybridization revealed miR-22 localization within fetal testicular cords. As estrogen signaling is important in human and sheep ovarian development, these data indicate that miR-22 is involved in repressing estrogen signaling within fetal testes. Conclusions Based on our results we postulate that gene expression networks underlying fetal gonadal development are regulated by miRNAs. PMID:21223560

  20. miReader: Discovering Novel miRNAs in Species without Sequenced Genome

    PubMed Central

    2013-01-01

    Along with computational approaches, NGS led technologies have caused a major impact upon the discoveries made in the area of miRNA biology, including novel miRNAs identification. However, to this date all microRNA discovery tools compulsorily depend upon the availability of reference or genomic sequences. Here, for the first time a novel approach, miReader, has been introduced which could discover novel miRNAs without any dependence upon genomic/reference sequences. The approach used NGS read data to build highly accurate miRNA models, molded through a Multi-boosting algorithm with Best-First Tree as its base classifier. It was comprehensively tested over large amount of experimental data from wide range of species including human, plants, nematode, zebrafish and fruit fly, performing consistently with >90% accuracy. Using the same tool over Illumina read data for Miscanthus, a plant whose genome is not sequenced; the study reported 21 novel mature miRNA duplex candidates. Considering the fact that miRNA discovery requires handling of high throughput data, the entire approach has been implemented in a standalone parallel architecture. This work is expected to cause a positive impact over the area of miRNA discovery in majority of species, where genomic sequence availability would not be a compulsion any more. PMID:23805282

  1. MiRNA-10b sponge: An anti-breast cancer study in vitro.

    PubMed

    Liang, Ai-Ling; Zhang, Ting-Ting; Zhou, Ning; Wu, Cui Yun; Lin, Man-Hua; Liu, Yong-Jun

    2016-04-01

    Breast cancer is a malignant tumor with the highest incidence among women. Breast cancer metastasis is the major cause of treatment failure and mortality among such patients. MicroRNAs (miRNAs) are a class of small molecular non-coding regulatory RNAs, which act as oncogenes or tumor suppressors in breast cancer. miRNA-10b has been found to exhibit a high expression level in advanced and metastatic breast cancer, and is closely related to breast cancer metastasis. An miRNA sponge is an mRNA with several repeated sequences of complete or incomplete complementarity to the natural miRNA in its 3' non-translating region. It acts as a sponge adsorbing miRNAs and ensures their separation from their targets and inhibits their function. The present study designed a sponge plasmid against miRNA-10b and transiently transfected it into high and low metastatic human breast cancer cell lines MDA-MB-231 and MCF-7, and analyzed the effects of the miRNA-10b sponge on the growth and proliferation, migration and invasion in these cell lines. qRT-PCR results found that the sponge plasmid effectively inhibited the expression of miRNA-10b, and upregulated the expression of the miRNA‑10b target protein HOXD-10. The results from the CCK-8 assay found that the miRNA-10b sponge inhibited the growth of breast cancer cell lines MDA-MB-231 and MCF-7. Results of the plate cloning experiments indicated that the miRNA-10b sponge suppressed the colony formation of the MDA-MB-231 and MCF-7 cells. The results of wound healing and Transwell assays showed that the miRNA-10b sponge inhibited the migration and invasion of the breast cancer cell lines MDA-MB-231 and MCF-7. Our results demonstrated that the miRNA-10b sponge effectively inhibited the growth and proliferation of breast cancer MDA-MB-231 and MCF-7 cells. In addition, it also restrained the migration and invasion of human highly metastatic breast cancer MDA-MB-231 cells.

  2. miRNA Expression Profiling Enables Risk Stratification in Archived and Fresh Neuroblastoma Tumor Samples

    PubMed Central

    De Preter, Katleen; Mestdagh, Pieter; Vermeulen, Joëlle; Zeka, Fjoralba; Naranjo, Arlene; Bray, Isabella; Castel, Victoria; Chen, Caifu; Drozynska, Elzbieta; Eggert, Angelika; Hogarty, Michael D.; Iżycka-Swieszewska, Ewa; London, Wendy B.; Noguera, Rosa; Piqueras, Marta; Bryan, Kenneth; Schowe, Benjamin; van Sluis, Peter; Molenaar, Jan J.; Schramm, Alexander; Schulte, Johannes H.; Stallings, Raymond L.; Versteeg, Rogier; Laureys, Geneviève; Van Roy, Nadine; Speleman, Frank; Vandesompele, Jo

    2012-01-01

    Purpose More accurate assessment of prognosis is important to further improve the choice of risk-related therapy in neuroblastoma (NB) patients. In this study, we aimed to establish and validate a prognostic miRNA signature for children with NB and tested it in both fresh frozen and archived formalin-fixed paraffin-embedded (FFPE) samples. Experimental Design Four hundred-thirty human mature miRNAs were profiled in two patient subgroups with maximally divergent clinical courses. Univariate logistic regression analysis was used to select miRNAs correlating with NB patient survival. A 25-miRNA gene signature was built using 51 training samples, tested on 179 test samples, and validated on an independent set of 304 fresh frozen tumor samples and 75 archived FFPE samples. Results The 25-miRNA signature significantly discriminates the test patients with respect to progression-free and overall survival (P < 0.0001), both in the overall population and in the cohort of high-risk patients. Multivariate analysis indicates that the miRNA signature is an independent predictor of patient survival after controlling for current risk factors. The results were confirmed in an external validation set. In contrast to a previously published mRNA classifier, the 25-miRNA signature was found to be predictive for patient survival in a set of 75 FFPE neuroblastoma samples. Conclusions In this study, we present the largest NB miRNA expression study so far, including more than 500 NB patients. We established and validated a robust miRNA classifier, able to identify a cohort of high-risk NB patients at greater risk for adverse outcome using both fresh frozen and archived material. PMID:22031095

  3. Changes in the miRNA profile under the influence of anabolic steroids in bovine liver.

    PubMed

    Becker, Christiane; Riedmaier, Irmgard; Reiter, Martina; Tichopad, Ales; Pfaffl, Michael W; Meyer, Heinrich H D

    2011-03-21

    miRNAs are regulatory RNA molecules. The analytical interest rose over the past 10 years especially in clinical diagnostics as miRNAs show specific expression patterns in several human diseases like diabetes or cancer. Therefore, it is expected that miRNA profiles might be used as biomarkers in early diagnosis. The idea of establishing biomarkers is also present in veterinary drug analysis, e.g. in the surveillance of illegal use of anabolics. Transcriptomics is a promising approach in the detection of anabolics misuse. However, miRNA expression patterns have shown their superiority over mRNA patterns in clinical diagnostics. Thus, the influence of anabolic steroids on miRNA expression in bovine liver should be investigated and an expression pattern should be validated, which might be used as a treatment biomarker. An animal experiment was conducted with 18 heifers equally allocated to a control and a treatment group, which was implanted with TBA plus E2. Liver samples were screened for miRNA expression using PCR arrays. Expression of 11 prominent miRNAs was validated via single assay qPCR. Herein, the following expression pattern could be found with an up-regulation of miR-29c and miR-103 and a down-regulation of miR-34a, miR-181c, miR-20a and miR-15a (p<0.05 each). Using principal components analysis (PCA), the control group could clearly be distinguished from the treatment group, when integrating gene expression results from both miRNA and mRNA. So, the combination of different transcribed targets (mRNA plus miRNA) might be a promising approach to find a valid expression pattern to be used for anabolic treatment screening.

  4. Joint Profiling of miRNAs and mRNAs Reveals miRNA Mediated Gene Regulation in the Göttingen Minipig Obesity Model

    PubMed Central

    Alkan, Ferhat; Keinicke, Helle; Jacobsen, Mette J.; Gorodkin, Jan; Fredholm, Merete; Cirera, Susanna

    2016-01-01

    Obesity and its comorbidities are an increasing challenge for both affected individuals and health care systems, worldwide. In obese individuals, perturbation of expression of both protein-coding genes and microRNAs (miRNA) are seen in obesity-relevant tissues (i.e. adipose tissue, liver and skeletal muscle). miRNAs are small non-coding RNA molecules which have important regulatory roles in a wide range of biological processes, including obesity. Rodents are widely used animal models for human diseases including obesity. However, not all research is applicable for human health or diseases. In contrast, pigs are emerging as an excellent animal model for obesity studies, due to their similarities in their metabolism, their digestive tract and their genetics, when compared to humans. The Göttingen minipig is a small sized easy-to-handle pig breed which has been extensively used for modeling human obesity, due to its capacity to develop severe obesity when fed ad libitum. The aim of this study was to identify differentially expressed of protein-coding genes and miRNAs in a Göttingen minipig obesity model. Liver, skeletal muscle and abdominal adipose tissue were sampled from 7 lean and 7 obese minipigs. Differential gene expression was investigated using high-throughput quantitative real-time PCR (qPCR) on 90 mRNAs and 72 miRNAs. The results revealed de-regulation of several obesity and inflammation-relevant protein-coding genes and miRNAs in all tissues examined. Many genes that are known to be de-regulated in obese humans were confirmed in the obese minipigs and several of these genes have target sites for miRNAs expressed in the opposing direction of the gene, confirming miRNA-mediated regulation in obesity. These results confirm the translational value of the pig for human obesity studies. PMID:27902747

  5. Fall 2014 SEI Research Review Applying Agile Methods to DoD

    DTIC Science & Technology

    2014-10-28

    2014 © 2014 Carnegie Mellon University Agile Defense Adoption Proponents Team (ADAPT) member E-Learning Agile Course Multiple Presentations ... presentations , program committees: GSAW 2014, Agile 2014, Contracts in Agile International Meeting, AFEI/SEI DoD Agile Summit, GAO Working Groups 8

  6. XP Workshop on Agile Product Line Engineering

    NASA Astrophysics Data System (ADS)

    Ghanam, Yaser; Cooper, Kendra; Abrahamsson, Pekka; Maurer, Frank

    Software Product Line Engineering (SPLE) promises to lower the costs of developing individual applications as they heavily reuse existing artifacts. Besides decreasing costs, software reuse achieves faster development and higher quality. Traditionally, SPLE favors big design upfront and employs traditional, heavy weight processes. On the other hand, agile methods have been proposed to rapidly develop high quality software by focusing on producing working code while reducing upfront analysis and design. Combining both paradigms, although is challenging, can yield significant improvements.

  7. Compact, Automated, Frequency-Agile Microspectrofluorimeter

    NASA Technical Reports Server (NTRS)

    Fernandez, Salvador M.; Guignon, Ernest F.

    1995-01-01

    Compact, reliable, rugged, automated cell-culture and frequency-agile microspectrofluorimetric apparatus developed to perform experiments involving photometric imaging observations of single live cells. In original application, apparatus operates mostly unattended aboard spacecraft; potential terrestrial applications include automated or semiautomated diagnosis of pathological tissues in clinical laboratories, biomedical instrumentation, monitoring of biological process streams, and portable instrumentation for testing biological conditions in various environments. Offers obvious advantages over present laboratory instrumentation.

  8. Diagnostic and prognostic significance of miRNA signatures in tissues and plasma of endometrioid endometrial carcinoma patients.

    PubMed

    Torres, Anna; Torres, Kamil; Pesci, Anna; Ceccaroni, Marcello; Paszkowski, Tomasz; Cassandrini, Paola; Zamboni, Giuseppe; Maciejewski, Ryszard

    2013-04-01

    The aim of our study was to define tissue and plasma miRNA signatures, which could potentially serve as diagnostic and prognostic markers in endometrioid endometrial cancer (EEC) and to investigate miRNA profiles in regard to clinicopathological characteristics. Tissue and plasma samples were collected from 122 women (77 EEC and 45 controls). Expression profiling of 866 human miRNAs and 89 human viral miRNAs was performed in 24 samples and was followed by qPCR validation in 104 patients. Expression of 16 miRNAs was analyzed in 48 plasma samples. Microarray study revealed regulation of 21 miRNAs in EEC tissues comparing to normal endometrium. Altered expression of 17 miRNAs was confirmed by qPCR performed in 104 tissue samples. Seven miRNAs were upregulated and two were downregulated in EEC plasma samples. Expression of a number of miRNAs was associated with International Federation of Gynecology and Obstetrics stage, grade, relapse and nodal metastases. Two miRNA signatures: miR-92a/miR-410 and miR-92a/miR-205/miR-410 classified tumor tissues with higher accuracy in comparison to single miRNAs (AUC: 0.977, 95% CI: 0.927-0.996 and 0.984, 95% CI: 0.938-0.999, respectively). miRNA signature composed of miR-205 and miR-200a predicted relapse with AUC of 0.854 (95% CI: 0.691-0.951). Tissue miRNA signatures were independent prognostic markers of overall (miR-1228/miR-200c/miR-429, HR: 2.98) and progression-free survival (miR-1228/miR-429, HR: 2.453). Plasma miRNA signatures: miR-9/miR-1228 and miR-9/miR-92a, classified EEC plasma samples with high accuracy yielding AUCs of 0.909 (95% CI: 0.789-973) and 0.913 (95% CI: 0.794-0.976), respectively. We conclude that miRNA signatures hold a great promise to become noninvasive biomarkers for early EEC detection and prognosis.

  9. RAS-MAPK pathway epigenetic activation in cancer: miRNAs in action

    PubMed Central

    Masliah-Planchon, Julien; Garinet, Simon; Pasmant, Eric

    2016-01-01

    The highly conserved RAS-mitogen activated protein kinase (MAPK) signaling pathway is involved in a wide range of cellular processes including differentiation, proliferation, and survival. Somatic mutations in genes encoding RAS-MAPK components frequently occur in many tumors, making the RAS-MAPK a critical pathway in human cancer. Since the pioneering study reporting that let-7 miRNA acted as tumor suppressor by repressing the RAS oncogene, growing evidence has suggested the importance of miRNAs targeting the RAS-MAPK in oncogenesis. MiRNAs alterations in human cancers may act as a rheostat of the oncogenic RAS signal that is often amplified as cancers progress. However, specific mechanisms leading to miRNAs deregulation and their functional consequences in cancer are far from being fully elucidated. In this review, we provide an experimental-validated map of RAS-MAPK oncomiRs and tumor suppressor miRNAs from transmembrane receptor to downstream ERK proteins. MiRNAs could be further considered as potential genetic biomarkers for diagnosis, prognosis, or therapeutic purpose. PMID:26646588

  10. In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation

    PubMed Central

    Palmieri, Dario; De Luca, Luciana; Consiglio, Jessica; You, Jia; Rocci, Alberto; Talabere, Tiffany; Piovan, Claudia; Lagana, Alessandro; Cascione, Luciano; Guan, Jingwen; Gasparini, Pierluigi; Balatti, Veronica; Nuovo, Gerard; Coppola, Vincenzo; Hofmeister, Craig C.; Marcucci, Guido; Byrd, John C.; Volinia, Stefano; Shapiro, Charles L.; Freitas, Michael A.

    2013-01-01

    Numerous studies have described the altered expression and the causal role of microRNAs (miRNAs) in human cancer. However, to date, efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here we find that nucleolin (NCL), a major nucleolar protein, posttranscriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, that are causally involved in breast cancer initiation, progression, and drug resistance. We also show that NCL is commonly overexpressed in human breast tumors and that its expression correlates with that of NCL-dependent miRNAs. Finally, inhibition of NCL using guanosine-rich aptamers reduces the levels of NCL-dependent miRNAs and their target genes, thus reducing breast cancer cell aggressiveness both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer. PMID:23610125

  11. MiRNAs and miRNA Polymorphisms Modify Drug Response

    PubMed Central

    Li, Mu-Peng; Hu, Yao-Dong; Hu, Xiao-Lei; Zhang, Yan-Jiao; Yang, Yong-Long; Jiang, Chun; Tang, Jie; Chen, Xiao-Ping

    2016-01-01

    Differences in expression of drug response-related genes contribute to inter-individual variation in drugs’ biological effects. MicroRNAs (miRNAs) are small noncoding RNAs emerging as new players in epigenetic regulation of gene expression at post-transcriptional level. MiRNAs regulate the expression of genes involved in drug metabolism, drug transportation, drug targets and downstream signal molecules directly or indirectly. MiRNA polymorphisms, the genetic variations affecting miRNA expression and/or miRNA-mRNA interaction, provide a new insight into the understanding of inter-individual difference in drug response. Here, we provide an overview of the recent progress in miRNAs mediated regulation of biotransformation enzymes, drug transporters, and nuclear receptors. We also describe the implications of miRNA polymorphisms in cancer chemotherapy response. PMID:27834829

  12. Aberration of miRNAs Expression in Leukocytes from Sporadic Amyotrophic Lateral Sclerosis

    PubMed Central

    Chen, YongPing; Wei, QianQian; Chen, XuePing; Li, ChunYu; Cao, Bei; Ou, RuWei; Hadano, Shinji; Shang, Hui-Fang

    2016-01-01

    Background: Accumulating evidence indicates that miRNAs play an important role in the development of amyotrophic lateral sclerosis (ALS). Most of previous studies on miRNA dysregulation in ALS focused on the alterative expression in ALS animal model or in limited samples from European patients with ALS. In the present study, the miRNA expression profiles were investigated in Chinese ALS patients to explore leukocytes miRNAs as a potential biomarker for the diagnosis of ALS. Methods: We analyzed the expression profiles of 1733 human mature miRNAs using microarray technology in leukocytes obtained from 5 patients with sporadic ALS (SALS) and 5 healthy controls. An independent group of 83 SALS patients, 24 Parkinson's disease (PD) patients and 61 controls was used for validation by real-time polymerase chain reaction assay. Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. In addition, target genes and signaling information of validated differential expression miRNAs were predicted using Bioinformatics. Results: Eleven miRNAs, including four over-expressed and seven under-expressed miRNAs detected in SALS patients compared to healthy controls were selected for validation. Four under-expressed microRNAs, including hsa-miR-183, hsa-miR-193b, hsa-miR-451, and hsa-miR-3935, were confirmed in validation stage by comparison of 83 SALS patients and 61 HCs. Moreover, we identified a miRNA panel (hsa-miR-183, hsa-miR-193b, hsa-miR-451, and hsa-miR-3935) having a high diagnostic accuracy of SALS (AUC 0.857 for the validation group). However, only hsa-miR-183 was significantly lower in SALS patients than that in PD patients and in HCs, while no differences were found between PD patients and HCs. By bioinformatics analysis, we obtained a large number of target genes and signaling information that are linked to neurodegeneration. Conclusion: This study provided evidence of abnormal miRNA expression patterns in the peripheral

  13. Future Research in Agile Systems Development: Applying Open Innovation Principles Within the Agile Organisation

    NASA Astrophysics Data System (ADS)

    Conboy, Kieran; Morgan, Lorraine

    A particular strength of agile approaches is that they move away from ‘introverted' development and intimately involve the customer in all areas of development, supposedly leading to the development of a more innovative and hence more valuable information system. However, we argue that a single customer representative is too narrow a focus to adopt and that involvement of stakeholders beyond the software development itself is still often quite weak and in some cases non-existent. In response, we argue that current thinking regarding innovation in agile development needs to be extended to include multiple stakeholders outside the business unit. This paper explores the intra-organisational applicability and implications of open innovation in agile systems development. Additionally, it argues for a different perspective of project management that includes collaboration and knowledge-sharing with other business units, customers, partners, and other relevant stakeholders pertinent to the business success of an organisation, thus embracing open innovation principles.

  14. Identification and comparative analyses of myocardial miRNAs involved in the fetal response to maternal obesity

    PubMed Central

    Muralimanoharan, Sribalasubashini; Huffman, Steven; Cox, Laura A.; Nathanielsz, Peter W.; Myatt, Leslie; Nijland, Mark J.

    2013-01-01

    Human and animal studies show that suboptimal intrauterine environments lead to fetal programming, predisposing offspring to disease in later life. Maternal obesity has been shown to program offspring for cardiovascular disease (CVD), diabetes, and obesity. MicroRNAs (miRNAs) are small, noncoding RNA molecules that act as key regulators of numerous cellular processes. Compelling evidence links miRNAs to the control of cardiac development and etiology of cardiac pathology; however, little is known about their role in the fetal cardiac response to maternal obesity. Our aim was to sequence and profile the cardiac miRNAs that are dysregulated in the hearts of baboon fetuses born to high fat/high fructose-diet (HFD) fed mothers for comparison with fetal hearts from mothers eating a regular diet. Eighty miRNAs were differentially expressed. Of those, 55 miRNAs were upregulated and 25 downregulated with HFD. Twenty-two miRNAs were mapped to human; 14 of these miRNAs were previously reported to be dysregulated in experimental or human CVD. We used an Ingenuity Pathway Analysis to integrate miRNA profiling and bioinformatics predictions to determine miRNA-regulated processes and genes potentially involved in fetal programming. We found a correlation between miRNA expression and putative gene targets involved in developmental disorders and CVD. Cellular death, growth, and proliferation were the most affected cellular functions in response to maternal obesity. Thus, the current study reveals significant alterations in cardiac miRNA expression in the fetus of obese baboons. The epigenetic modifications caused by adverse prenatal environment may represent one of the mechanisms underlying fetal programming of CVD. PMID:23922128

  15. Rolling and tumbling: status of the SuperAGILE experiment

    NASA Astrophysics Data System (ADS)

    Del Monte, E.; Costa, E.; di Persio, G.; Donnarumma, I.; Evangelista, Y.; Feroci, M.; Lapshov, I.; Lazzarotto, F.; Mastropietro, M.; Morelli, E.; Pacciani, L.; Rapisarda, M.; Rubini, A.; Soffitta, P.; Tavani, M.; Argan, A.; Trois, A.

    2010-07-01

    The SuperAGILE experiment is the hard X-ray monitor of the AGILE mission. It is a 2 x one-dimensional imager, with 6-arcmin angular resolution in the energy range 18 - 60 keV and a field of view in excess of 1 steradian. SuperAGILE is successfully operating in orbit since Summer 2007, providing long-term monitoring of bright sources and prompt detection and localization of gamma-ray bursts. Starting on October 2009 the AGILE mission lost its reaction wheel and the satellite attitude is no longer stabilized. The current mode of operation of the AGILE satellite is a Spinning Mode, around the Sun-pointing direction, with an angular velocity of about 0.8 degree/s (corresponding to 8 times the SuperAGILE point spread function every second). In these new conditions, SuperAGILE continuously scans a much larger fraction of the sky, with much smaller exposure to each region. In this paper we review some of the results of the first 2.5 years of "standard" operation of SuperAGILE, and show how new implementations in the data analysis software allows to continue the hard X-ray sky monitoring by SuperAGILE also in the new attitude conditions.

  16. Applying Agile MethodstoWeapon/Weapon-Related Software

    SciTech Connect

    Adams, D; Armendariz, M; Blackledge, M; Campbell, F; Cloninger, M; Cox, L; Davis, J; Elliott, M; Granger, K; Hans, S; Kuhn, C; Lackner, M; Loo, P; Matthews, S; Morrell, K; Owens, C; Peercy, D; Pope, G; Quirk, R; Schilling, D; Stewart, A; Tran, A; Ward, R; Williamson, M

    2007-05-02

    This white paper provides information and guidance to the Department of Energy (DOE) sites on Agile software development methods and the impact of their application on weapon/weapon-related software development. The purpose of this white paper is to provide an overview of Agile methods, examine the accepted interpretations/uses/practices of these methodologies, and discuss the applicability of Agile methods with respect to Nuclear Weapons Complex (NWC) Technical Business Practices (TBPs). It also provides recommendations on the application of Agile methods to the development of weapon/weapon-related software.

  17. miRNAs associated with immune response in teleost fish.

    PubMed

    Andreassen, Rune; Høyheim, Bjørn

    2017-02-28

    MicroRNAs (miRNAs) have been identified as important post transcriptional regulators of gene expression. In higher vertebrates, a subset of miRNAs has been identified as important regulators of a number of key genes in immune system gene networks, and this paper review recent studies on miRNAs associated with immune response in teleost fish. Challenge studies conducted in several species have identified differently expressed miRNAs associated with viral or bacterial infection. The results from these studies point out several miRNAs that are likely to have evolutionary conserved functions that are related to immune response in teleost fish. Changed expression levels of mature miRNAs from the five miRNA genes miRNA-462, miRNA-731, miRNA-146, miRNA-181 and miRNA-223 are observed following viral as well as bacterial infection in several teleost fish. Furthermore, significant changes in expression of mature miRNAs from the five genes miRNA-21, miRNA-155, miRNA-1388, miRNA-99 and miRNA-100 are observed in multiple studies of virus infected fish while changes in expression of mature miRNA from the three genes miRNA-122, miRNA-192 and miRNA-451 are observed in several studies of fish with bacterial infections. Interestingly, some of these genes are not present in higher vertebrates. The function of the evolutionary conserved miRNAs responding to infection depends on the target gene(s) they regulate. A few target genes have been identified while a large number of target genes have been predicted by in silico analysis. The results suggest that many of the targets are genes from the host's immune response gene networks. We propose a model with expected temporal changes in miRNA expression if they target immune response activators/effector genes or immune response inhibitors, respectively. The best way to understand the function of a miRNA is to identify its target gene(s), but as the amount of genome resources for teleost fish is limited, with less well characterized genomes

  18. mirPRo–a novel standalone program for differential expression and variation analysis of miRNAs

    PubMed Central

    Shi, Jieming; Dong, Min; Li, Lei; Liu, Lin; Luz-Madrigal, Agustin; Tsonis, Panagiotis A.; Del Rio-Tsonis, Katia; Liang, Chun

    2015-01-01

    Being involved in many important biological processes, miRNAs can regulate gene expression by targeting mRNAs to facilitate their degradation or translational inhibition. Many miRNA sequencing studies reveal that miRNA variations such as isomiRs and “arm switching” are biologically relevant. However, existing standalone tools usually do not provide comprehensive, detailed information on miRNA variations. To deepen our understanding of miRNA variability, we developed a new standalone tool called “mirPRo” to quantify known miRNAs and predict novel miRNAs. Compared with the most widely used standalone program, miRDeep2, mirPRo offers several new functions including read cataloging based on genome annotation, optional seed region check, miRNA family expression quantification, isomiR identification and categorization, and “arm switching” detection. Our comparative data analyses using three datasets from mouse, human and chicken demonstrate that mirPRo is more accurate than miRDeep2 by avoiding over-counting of sequence reads and by implementing different approaches in adapter trimming, mapping and quantification. mirPRo is an open-source standalone program (https://sourceforge.net/projects/mirpro/). PMID:26434581

  19. A PCR-Based Method to Construct Lentiviral Vector Expressing Double Tough Decoy for miRNA Inhibition

    PubMed Central

    Luo, Lan; Liu, Nian; Kang, Kang; Qu, Junle; Peng, Wenda; Gou, Deming

    2015-01-01

    DNA vector-encoded Tough Decoy (TuD) miRNA inhibitor is attracting increased attention due to its high efficiency in miRNA suppression. The current methods used to construct TuD vectors are based on synthesizing long oligonucleotides (~90 mer), which have been costly and problematic because of mutations during synthesis. In this study, we report a PCR-based method for the generation of double Tough Decoy (dTuD) vector in which only two sets of shorter oligonucleotides (< 60 mer) were used. Different approaches were employed to test the inhibitory potency of dTuDs. We demonstrated that dTuD is the most efficient method in miRNA inhibition in vitro and in vivo. Using this method, a mini dTuD library against 88 human miRNAs was constructed and used for a high-throughput screening (HTS) of AP-1 pathway-related miRNAs. Seven miRNAs (miR-18b-5p, -101-3p, -148b-3p, -130b-3p, -186-3p, -187-3p and -1324) were identified as candidates involved in AP-1 pathway regulation. This novel method allows for an accurate and cost-effective generation of dTuD miRNA inhibitor, providing a powerful tool for efficient miRNA suppression in vitro and in vivo. PMID:26624995

  20. The role of miRNAs in the regulation of inflammatory processes during hepatofibrogenesis

    PubMed Central

    Roy, Sanchari; Benz, Fabian; Luedde, Tom

    2015-01-01

    Liver cirrhosis represents the end stage of most chronic inflammatory liver diseases and is a major global health burden. Despite the enormous relevance of cirrhotic disease, pharmacological strategies for prevention or treatment of hepatic fibrosis are still limited, underlining the need to establish a better understanding of the molecular mechanisms underlying the pathogenesis of hepatic cirrhosis. Recently, miRNAs have emerged as a new class of RNAs that do not withhold the information to encode for proteins but regulate whole gene expression networks during different physiological and pathological processes. Various authors demonstrated that miRNA species are functionally involved in the regulation of chronic liver damage and development of liver cirrhosis in inflamed livers. Moreover, circulating miRNA patterns were suggested to serve as blood-based biomarkers indicating liver injury and progression to hepatic cirrhosis and cancer. Here we summarize current findings on a potential role of miRNAs in the cascade leading from liver inflammation to liver fibrosis and finally hepatocellular carcinoma. We compare data from animal models with findings on miRNAs dysregulated in human patients and finally highlight a potential use of miRNAs as biomarkers for liver injury, fibrosis and cancer. PMID:25713802

  1. Hippo signaling regulates Microprocessor and links cell density-dependent miRNA biogenesis to cancer

    PubMed Central

    Mori, Masaki; Triboulet, Robinson; Mohseni, Morvarid; Schlegelmilch, Karin; Shrestha, Kriti; Camargo, Fernando D.; Gregory, Richard I.

    2014-01-01

    SUMMARY Global downregulation of microRNAs (miRNAs) is commonly observed in human cancers and can have a causative role in tumorigenesis. The mechanisms responsible for this phenomenon remain poorly understood. Here we show that YAP, the downstream target of the tumor-suppressive Hippo signaling pathway regulates miRNA biogenesis in a cell density-dependent manner. At low cell density, nuclear YAP binds and sequesters p72 (DDX17), a regulatory component of the miRNA processing machinery. At high cell density, Hippo-mediated cytoplasmic retention of YAP facilitates p72 association with Microprocessor and binding to a specific sequence motif in pri-miRNAs. Inactivation of the Hippo pathway or expression of constitutively active YAP causes widespread miRNA suppression in cells and tumors and a corresponding post-transcriptional induction of MYC expression. Thus, the Hippo pathway links contact-inhibition regulation to miRNA biogenesis and may be responsible for the widespread miRNA repression observed in cancer. PMID:24581491

  2. The Role of miRNAs in Common Inflammatory Arthropathies: Osteoarthritis and Gouty Arthritis

    PubMed Central

    Papanagnou, Panagiota; Stivarou, Theodora; Tsironi, Maria

    2016-01-01

    MicroRNAs (miRNAs) are small, non-coding RNA species that are highly evolutionarily conserved, from higher invertebrates to man. Up to 1000 miRNAs have been identified in human cells thus far, where they are key regulators of the expression of numerous targets at the post-transcriptional level. They are implicated in various processes, including cell differentiation, metabolism, and inflammation. An expanding list of miRNAs is known to be involved in the pathogenesis of common, non-autoimmune inflammatory diseases. Interestingly, osteoarthritis (OA) is now being conceptualized as a metabolic disease, as there is a correlation among hyperuricemia and metabolic syndrome (MetS). Experimental evidence suggests that metabolic deregulation is a commonality between these different pathological entities, and that miRNAs are key players in the modulation of metabolic routes. In light of these findings, this review discusses the role of miRNAs in OA and gouty arthritis, as well as the possible therapeutic targetability of miRNAs in these diseases. PMID:27845712

  3. Detection of Exosomal miRNAs in the Plasma of Melanoma Patients

    PubMed Central

    Pfeffer, Susan R.; Grossmann, Kenneth F.; Cassidy, Pamela B.; Yang, Chuan He; Fan, Meiyun; Kopelovich, Levy; Leachman, Sancy A.; Pfeffer, Lawrence M.

    2015-01-01

    MicroRNAs (miRNAs) are a class of 22–25 nucleotide RNAs that control gene expression at the post-transcriptional level. MiRNAs have potential as cancer biomarkers. Melanoma is a highly aggressive form of skin cancer accounting for almost 4% of cancers among men and women, and ~80% of skin cancer-related deaths in the US. In the present study we analyzed plasma-derived exosomal miRNAs from clinically affected and unaffected familial melanoma patients (CDKN2A/p16 gene carriers) and compared them with affected (nonfamilial melanoma) and unaffected control subjects in order to identify novel risk biomarkers for melanoma. Intact miRNAs can be isolated from the circulation because of their presence in exosomes. A number of differentially regulated miRNAs identified by NanoString human V2 miRNA array were validated by quantitative PCR. Significantly, miR-17, miR-19a, miR-21, miR-126, and miR-149 were expressed at higher levels in patients with metastatic sporadic melanoma as compared with familial melanoma patients or unaffected control subjects. Surprisingly, no substantial differences in miRNA expression were detected between familial melanoma patients (all inclusive) and unaffected control subjects. The miRNAs differentially expressed in the different patient cohorts, especially in patients with metastatic melanoma, may play important roles in tumor progression and metastasis, and may be used as predictive biomarkers to monitor remission as well as relapse following therapeutic intervention. PMID:26694476

  4. Pluripotent and Multipotent Stem Cells Display Distinct Hypoxic miRNA Expression Profiles

    PubMed Central

    Agrawal, Rahul; Dale, Tina P.; Al-Zubaidi, Mohammed A.; Benny Malgulwar, Prit; Forsyth, Nicholas R.; Kulshreshtha, Ritu

    2016-01-01

    MicroRNAs are reported to have a crucial role in the regulation of self-renewal and differentiation of stem cells. Hypoxia has been identified as a key biophysical element of the stem cell culture milieu however, the link between hypoxia and miRNA expression in stem cells remains poorly understood. We therefore explored miRNA expression in hypoxic human embryonic and mesenchymal stem cells (hESCs and hMSCs). A total of 50 and 76 miRNAs were differentially regulated by hypoxia (2% O2) in hESCs and hMSCs, respectively, with a negligible overlap of only three miRNAs. We found coordinate regulation of precursor and mature miRNAs under hypoxia suggesting their regulation mainly at transcriptional level. Hypoxia response elements were located upstream of 97% of upregulated hypoxia regulated miRNAs (HRMs) suggesting hypoxia-inducible-factor (HIF) driven transcription. HIF binding to the candidate cis-elements of specific miRNAs under hypoxia was confirmed by Chromatin immunoprecipitation coupled with qPCR. Role analysis of a subset of upregulated HRMs identified linkage to reported inhibition of differentiation while a downregulated subset of HRMs had a putative role in the promotion of differentiation. MiRNA-target prediction correlation with published hypoxic hESC and hMSC gene expression profiles revealed HRM target genes enriched in the cytokine:cytokine receptor, HIF signalling and pathways in cancer. Overall, our study reveals, novel and distinct hypoxia-driven miRNA signatures in hESCs and hMSCs with the potential for application in optimised culture and differentiation models for both therapeutic application and improved understanding of stem cell biology. PMID:27783707

  5. Agile Data Curation: A conceptual framework and approach for practitioner data management

    NASA Astrophysics Data System (ADS)

    Young, J. W.; Benedict, K. K.; Lenhardt, W. C.

    2015-12-01

    Data management occurs across a range of science and related activities such as decision-support. Exemplars within the science community operate data management systems that are extensively planned before implementation, staffed with robust data management expertise, equipped with appropriate services and technologies, and often highly structured. However, this is not the only approach to data management and almost certainly not the typical experience. The other end of the spectrum is often an ad hoc practitioner team, with changing requirements, limited training in data management, and resource constrained for both equipment and human resources. Much of the existing data management literature serves the exemplar community and ignores the ad hoc practitioners. Somewhere in the middle are examples where data are repurposed for new uses thereby generating new data management challenges. This submission presents a conceptualization of an Agile Data Curation approach that provides foundational principles for data management efforts operating across the spectrum of data generation and use from large science systems to efforts with constrained resources, limited expertise, and evolving requirements. The underlying principles to Agile Data Curation are a reapplication of agile software development principles to data management. The historical reality for many data management efforts is operating in a practioner environment so Agile Data Curation utilizes historical and current case studies to validate the foundational principles and through comparison learn lessons for future application. This submission will provide an overview of the Agile Data Curation, cover the foundational principles to the approach, and introduce a framework for gathering, classifying, and applying lessons from case studies of practitioner data management.

  6. Agile informatics: application of agile project management to the development of a personal health application.

    PubMed

    Chung, Jeanhee; Pankey, Evan; Norris, Ryan J

    2007-10-11

    We describe the application of the Agile method-- a short iteration cycle, user responsive, measurable software development approach-- to the project management of a modular personal health record, iHealthSpace, to be deployed to the patients and providers of a large academic primary care practice.

  7. Agile Development Methods for Space Operations

    NASA Technical Reports Server (NTRS)

    Trimble, Jay; Webster, Chris

    2012-01-01

    Main stream industry software development practice has gone from a traditional waterfall process to agile iterative development that allows for fast response to customer inputs and produces higher quality software at lower cost. How can we, the space ops community, adopt state of the art software development practice, achieve greater productivity at lower cost, and maintain safe and effective space flight operations? At NASA Ames, we are developing Mission Control Technologies Software, in collaboration with Johnson Space Center (JSC) and, more recently, the Jet Propulsion Laboratory (JPL).

  8. Modelling fire-fighter responses to exercise and asymmetric infrared radiation using a dynamic multi-mode model of human physiology and results from the sweating agile thermal manikin.

    PubMed

    Richards, M G M; Fiala, D

    2004-09-01

    In this study, predicted dynamic physiological responses are compared with wear trials results for firefighter suits: impermeable (A), semi-permeable (B) and permeable (C), and underwear. Wear trials consisted of three rest phases and two moderate work phases, with a frontal infrared (IR) radiation exposure of 500 W/m2 for the last 15 min of each work phase. Simulations were performed by detailed modelling of the experimental boundary conditions, including the inhomogeneous IR radiation combined with clothing properties for still and walking conditions measured using the Sweating Agile thermal Manikin. Accounting for the effect of sweat gland activity suppression with increased skin wettedness, the predicted total moisture loss was insignificantly different (P<0.05) from the wear trial value for suits B and C but was 37% too high for suit A. Predicted evolution of core, mean skin and local skin temperatures agreed well with the wear trial results for all clothing. Root mean square deviations ranged from 0.11 degrees C to 0.26 degrees C for core temperatures and from 0.28 degrees C to 0.38 degrees C for mean skin temperatures, which where typically lower than the experimental error. Transient thermodynamic processes occurring within suit A may account for the delayed/reduced fall in core temperature following exercise.

  9. A Roadmap for Using Agile Development in a Traditional Environment

    NASA Technical Reports Server (NTRS)

    Streiffert, Barbara; Starbird, Thomas; Grenander, Sven

    2006-01-01

    One of the newer classes of software engineering techniques is called 'Agile Development'. In Agile Development software engineers take small implementation steps and, in some cases, they program in pairs. In addition, they develop automatic tests prior to implementing their small functional piece. Agile Development focuses on rapid turnaround, incremental planning, customer involvement and continuous integration. Agile Development is not the traditional waterfall method or even a rapid prototyping method (although this methodology is closer to Agile Development). At the Jet Propulsion Laboratory (JPL) a few groups have begun Agile Development software implementations. The difficulty with this approach becomes apparent when Agile Development is used in an organization that has specific criteria and requirements handed down for how software development is to be performed. The work at the JPL is performed for the National Aeronautics and Space Agency (NASA). Both organizations have specific requirements, rules and processes for developing software. This paper will discuss some of the initial uses of the Agile Development methodology, the spread of this method and the current status of the successful incorporation into the current JPL development policies and processes.

  10. A Roadmap for Using Agile Development in a Traditional Environment

    NASA Technical Reports Server (NTRS)

    Streiffert, Barbara A.; Starbird, Thomas; Grenander, Sven

    2006-01-01

    One of the newer classes of software engineering techniques is called 'Agile Development'. In Agile Development software engineers take small implementation steps and, in some cases they program in pairs. In addition, they develop automatic tests prior to implementing their small functional piece. Agile Development focuses on rapid turnaround, incremental planning, customer involvement and continuous integration. Agile Development is not the traditional waterfall method or even a rapid prototyping method (although this methodology is closer to Agile Development). At Jet Propulsion Laboratory (JPL) a few groups have begun Agile Development software implementations. The difficulty with this approach becomes apparent when Agile Development is used in an organization that has specific criteria and requirements handed down for how software development is to be performed. The work at the JPL is performed for the National Aeronautics and Space Agency (NASA). Both organizations have specific requirements, rules and procedure for developing software. This paper will discuss the some of the initial uses of the Agile Development methodology, the spread of this method and the current status of the successful incorporation into the current JPL development policies.

  11. Agile manufacturing in Intelligence, Surveillance and Reconnaissance (ISR)

    NASA Astrophysics Data System (ADS)

    DiPadua, Mark; Dalton, George

    2016-05-01

    The objective of the Agile Manufacturing for Intelligence, Surveillance, and Reconnaissance (AMISR) effort is to research, develop, design and build a prototype multi-intelligence (multi-INT), reconfigurable pod demonstrating benefits of agile manufacturing and a modular open systems approach (MOSA) to make podded intelligence, surveillance, and reconnaissance (ISR) capability more affordable and operationally flexible.

  12. Peridigm summary report : lessons learned in development with agile components.

    SciTech Connect

    Salinger, Andrew Gerhard; Mitchell, John Anthony; Littlewood, David John; Parks, Michael L.

    2011-09-01

    This report details efforts to deploy Agile Components for rapid development of a peridynamics code, Peridigm. The goal of Agile Components is to enable the efficient development of production-quality software by providing a well-defined, unifying interface to a powerful set of component-based software. Specifically, Agile Components facilitate interoperability among packages within the Trilinos Project, including data management, time integration, uncertainty quantification, and optimization. Development of the Peridigm code served as a testbed for Agile Components and resulted in a number of recommendations for future development. Agile Components successfully enabled rapid integration of Trilinos packages into Peridigm. A cost of this approach, however, was a set of restrictions on Peridigm's architecture which impacted the ability to track history-dependent material data, dynamically modify the model discretization, and interject user-defined routines into the time integration algorithm. These restrictions resulted in modifications to the Agile Components approach, as implemented in Peridigm, and in a set of recommendations for future Agile Components development. Specific recommendations include improved handling of material states, a more flexible flow control model, and improved documentation. A demonstration mini-application, SimpleODE, was developed at the onset of this project and is offered as a potential supplement to Agile Components documentation.

  13. Development of an agility assessment module for preliminary fighter design

    NASA Technical Reports Server (NTRS)

    Ngan, Angelen; Bauer, Brent; Biezad, Daniel; Hahn, Andrew

    1996-01-01

    A FORTRAN computer program is presented to perform agility analysis on fighter aircraft configurations. This code is one of the modules of the NASA Ames ACSYNT (AirCraft SYNThesis) design code. The background of the agility research in the aircraft industry and a survey of a few agility metrics are discussed. The methodology, techniques, and models developed for the code are presented. FORTRAN programs were developed for two specific metrics, CCT (Combat Cycle Time) and PM (Pointing Margin), as part of the agility module. The validity of the code was evaluated by comparing with existing flight test data. Example trade studies using the agility module along with ACSYNT were conducted using Northrop F-20 Tigershark and McDonnell Douglas F/A-18 Hornet aircraft models. The sensitivity of thrust loading and wing loading on agility criteria were investigated. The module can compare the agility potential between different configurations and has the capability to optimize agility performance in the preliminary design process. This research provides a new and useful design tool for analyzing fighter performance during air combat engagements.

  14. Agile Methods for Open Source Safety-Critical Software

    PubMed Central

    Enquobahrie, Andinet; Ibanez, Luis; Cheng, Patrick; Yaniv, Ziv; Cleary, Kevin; Kokoori, Shylaja; Muffih, Benjamin; Heidenreich, John

    2011-01-01

    The introduction of software technology in a life-dependent environment requires the development team to execute a process that ensures a high level of software reliability and correctness. Despite their popularity, agile methods are generally assumed to be inappropriate as a process family in these environments due to their lack of emphasis on documentation, traceability, and other formal techniques. Agile methods, notably Scrum, favor empirical process control, or small constant adjustments in a tight feedback loop. This paper challenges the assumption that agile methods are inappropriate for safety-critical software development. Agile methods are flexible enough to encourage the right amount of ceremony; therefore if safety-critical systems require greater emphasis on activities like formal specification and requirements management, then an agile process will include these as necessary activities. Furthermore, agile methods focus more on continuous process management and code-level quality than classic software engineering process models. We present our experiences on the image-guided surgical toolkit (IGSTK) project as a backdrop. IGSTK is an open source software project employing agile practices since 2004. We started with the assumption that a lighter process is better, focused on evolving code, and only adding process elements as the need arose. IGSTK has been adopted by teaching hospitals and research labs, and used for clinical trials. Agile methods have matured since the academic community suggested they are not suitable for safety-critical systems almost a decade ago, we present our experiences as a case study for renewing the discussion. PMID:21799545

  15. Integrated product definition representation for agile numerical control applications

    SciTech Connect

    Simons, W.R. Jr.; Brooks, S.L.; Kirk, W.J. III; Brown, C.W.

    1994-11-01

    Realization of agile manufacturing capabilities for a virtual enterprise requires the integration of technology, management, and work force into a coordinated, interdependent system. This paper is focused on technology enabling tools for agile manufacturing within a virtual enterprise specifically relating to Numerical Control (N/C) manufacturing activities and product definition requirements for these activities.

  16. Agile Methods for Open Source Safety-Critical Software.

    PubMed

    Gary, Kevin; Enquobahrie, Andinet; Ibanez, Luis; Cheng, Patrick; Yaniv, Ziv; Cleary, Kevin; Kokoori, Shylaja; Muffih, Benjamin; Heidenreich, John

    2011-08-01

    The introduction of software technology in a life-dependent environment requires the development team to execute a process that ensures a high level of software reliability and correctness. Despite their popularity, agile methods are generally assumed to be inappropriate as a process family in these environments due to their lack of emphasis on documentation, traceability, and other formal techniques. Agile methods, notably Scrum, favor empirical process control, or small constant adjustments in a tight feedback loop. This paper challenges the assumption that agile methods are inappropriate for safety-critical software development. Agile methods are flexible enough to encourage the rightamount of ceremony; therefore if safety-critical systems require greater emphasis on activities like formal specification and requirements management, then an agile process will include these as necessary activities. Furthermore, agile methods focus more on continuous process management and code-level quality than classic software engineering process models. We present our experiences on the image-guided surgical toolkit (IGSTK) project as a backdrop. IGSTK is an open source software project employing agile practices since 2004. We started with the assumption that a lighter process is better, focused on evolving code, and only adding process elements as the need arose. IGSTK has been adopted by teaching hospitals and research labs, and used for clinical trials. Agile methods have matured since the academic community suggested they are not suitable for safety-critical systems almost a decade ago, we present our experiences as a case study for renewing the discussion.

  17. Transcriptional regulation of mammalian miRNA genes

    PubMed Central

    Schanen, Brian C.; Li, Xiaoman

    2010-01-01

    MicroRNAs (miRNAs) are members of a growing family of non-coding transcripts, 21-23 nucleotides long, which regulate a diverse collection of biological processes and various diseases by RNA-mediated gene-silencing mechanisms. While currently many studies focus on defining the regulatory functions of miRNAs, few are directed towards how miRNA genes are themselves transcriptionally regulated. Recent studies of miRNA transcription have elucidated RNA polymerase II as the major polymerase of miRNAs, however, little is known of the structural features of miRNA promoters, especially those of mammalian miRNAs. Here, we review the current literature regarding features conserved among miRNA promoters useful for their detection and the current novel methodologies available to enable researchers to advance our understanding of the transcriptional regulation of miRNA genes. PMID:20977933

  18. A Case Study of Coordination in Distributed Agile Software Development

    NASA Astrophysics Data System (ADS)

    Hole, Steinar; Moe, Nils Brede

    Global Software Development (GSD) has gained significant popularity as an emerging paradigm. Companies also show interest in applying agile approaches in distributed development to combine the advantages of both approaches. However, in their most radical forms, agile and GSD can be placed in each end of a plan-based/agile spectrum because of how work is coordinated. We describe how three GSD projects applying agile methods coordinate their work. We found that trust is needed to reduce the need of standardization and direct supervision when coordinating work in a GSD project, and that electronic chatting supports mutual adjustment. Further, co-location and modularization mitigates communication problems, enables agility in at least part of a GSD project, and renders the implementation of Scrum of Scrums possible.

  19. Visual Display of 5p-arm and 3p-arm miRNA Expression with a Mobile Application.

    PubMed

    Pan, Chao-Yu; Kuo, Wei-Ting; Chiu, Chien-Yuan; Lin, Wen-Chang

    2017-01-01

    MicroRNAs (miRNAs) play important roles in human cancers. In previous studies, we have demonstrated that both 5p-arm and 3p-arm of mature miRNAs could be expressed from the same precursor and we further interrogated the 5p-arm and 3p-arm miRNA expression with a comprehensive arm feature annotation list. To assist biologists to visualize the differential 5p-arm and 3p-arm miRNA expression patterns, we utilized a user-friendly mobile App to display. The Cancer Genome Atlas (TCGA) miRNA-Seq expression information. We have collected over 4,500 miRNA-Seq datasets from 15 TCGA cancer types and further processed them with the 5p-arm and 3p-arm annotation analysis pipeline. In order to be displayed with the RNA-Seq Viewer App, annotated 5p-arm and 3p-arm miRNA expression information and miRNA gene loci information were converted into SQLite tables. In this distinct application, for any given miRNA gene, 5p-arm miRNA is illustrated on the top of chromosome ideogram and 3p-arm miRNA is illustrated on the bottom of chromosome ideogram. Users can then easily interrogate the differentially 5p-arm/3p-arm expressed miRNAs with their mobile devices. This study demonstrates the feasibility and utility of RNA-Seq Viewer App in addition to mRNA-Seq data visualization.

  20. Visual Display of 5p-arm and 3p-arm miRNA Expression with a Mobile Application

    PubMed Central

    Pan, Chao-Yu; Kuo, Wei-Ting; Chiu, Chien-Yuan

    2017-01-01

    MicroRNAs (miRNAs) play important roles in human cancers. In previous studies, we have demonstrated that both 5p-arm and 3p-arm of mature miRNAs could be expressed from the same precursor and we further interrogated the 5p-arm and 3p-arm miRNA expression with a comprehensive arm feature annotation list. To assist biologists to visualize the differential 5p-arm and 3p-arm miRNA expression patterns, we utilized a user-friendly mobile App to display. The Cancer Genome Atlas (TCGA) miRNA-Seq expression information. We have collected over 4,500 miRNA-Seq datasets from 15 TCGA cancer types and further processed them with the 5p-arm and 3p-arm annotation analysis pipeline. In order to be displayed with the RNA-Seq Viewer App, annotated 5p-arm and 3p-arm miRNA expression information and miRNA gene loci information were converted into SQLite tables. In this distinct application, for any given miRNA gene, 5p-arm miRNA is illustrated on the top of chromosome ideogram and 3p-arm miRNA is illustrated on the bottom of chromosome ideogram. Users can then easily interrogate the differentially 5p-arm/3p-arm expressed miRNAs with their mobile devices. This study demonstrates the feasibility and utility of RNA-Seq Viewer App in addition to mRNA-Seq data visualization. PMID:28271066

  1. Serum-circulating miRNAs predict neuroblastoma progression in mouse model of high-risk metastatic disease

    PubMed Central

    Ramraj, Satish Kumar; Aravindan, Sheeja; Somasundaram, Dinesh Babu; Herman, Terence S.; Natarajan, Mohan; Aravindan, Natarajan

    2016-01-01

    Background Circulating miRNAs have momentous clinical relevance as prognostic biomarkers and in the progression of solid tumors. Recognizing novel candidates of neuroblastoma-specific circulating miRNAs would allow us to identify potential prognostic biomarkers that could predict the switch from favorable to high-risk metastatic neuroblastoma (HR-NB). Results Utilizing mouse models of favorable and HR-NB and whole miRnome profiling, we identified high serum levels of 34 and low levels of 46 miRNAs in animals with HR-NB. Preferential sequence homology exclusion of mouse miRNAs identified 25 (11 increased; 14 decreased) human-specific prognostic marker candidates, of which, 21 were unique to HR-NB. miRNA QPCR validated miRnome profile. Target analysis defined the candidate miRNAs' signal transduction flow-through and demonstrated their converged roles in tumor progression. miRNA silencing studies verified the function of select miRNAs on the translation of at least 14 target proteins. Expressions of critical targets that correlate tumor progression in tissue of multifarious organs identify the orchestration of HR-NB. Significant (>10 fold) increase in serum levels of miR-381, miR-548h, and miR-580 identify them as potential prognostic markers for neuroblastoma progression. Conclusion For the first time, we identified serum-circulating miRNAs that predict the switch from favorable to HR-NB and, further imply that these miRNAs could play a functional role in tumor progression. PMID:26921195

  2. Use of Mature miRNA Strand Selection in miRNAs Families in Cervical Cancer Development.

    PubMed

    Granados-López, Angelica Judith; Ruiz-Carrillo, José Luis; Servín-González, Luis Steven; Martínez-Rodríguez, José Luis; Reyes-Estrada, Claudia Araceli; Gutiérrez-Hernández, Rosalinda; López, Jesús Adrián

    2017-02-14

    Aberrant miRNA expression is well recognized as a cancer hallmark, nevertheless miRNA function and expression does not always correlate in patients tissues and cell lines studies. In addition to this issue, miRNA strand usage conduces to increased cell signaling pathways modulation diversifying cellular processes regulation. In cervical cancer, 20 miRNA families are involved in carcinogenesis induction and development to this moment. These families have 5p and 3p strands with different nucleotide (nt) chain sizes. In general, mature 5p strands are larger: two miRNAs of 24 nt, 24 miRNAs of 23 nt, 35 miRNAs of 22 nt and three miRNAs of 21 nt. On the other hand, the 3p strands lengths observed are: seven miRNAs of 23 nt, 50 miRNAs of 22 nt, six miRNAs of 21 nt and four miRNAs of 20 nt. Based on the analysis of the 20 miRNA families associated with cervical cancer, 67 3p strands and 65 5p strands are selected suggesting selectivity and specificity mechanisms regulating cell processes like proliferation, apoptosis, migration, invasion, metabolism and Warburg effect. The insight reviewed here could be used in the miRNA based therapy, diagnosis and prognosis approaches.

  3. Use of Mature miRNA Strand Selection in miRNAs Families in Cervical Cancer Development

    PubMed Central

    Granados-López, Angelica Judith; Ruiz-Carrillo, José Luis; Servín-González, Luis Steven; Martínez-Rodríguez, José Luis; Reyes-Estrada, Claudia Araceli; Gutiérrez-Hernández, Rosalinda; López, Jesús Adrián

    2017-01-01

    Aberrant miRNA expression is well recognized as a cancer hallmark, nevertheless miRNA function and expression does not always correlate in patients tissues and cell lines studies. In addition to this issue, miRNA strand usage conduces to increased cell signaling pathways modulation diversifying cellular processes regulation. In cervical cancer, 20 miRNA families are involved in carcinogenesis induction and development to this moment. These families have 5p and 3p strands with different nucleotide (nt) chain sizes. In general, mature 5p strands are larger: two miRNAs of 24 nt, 24 miRNAs of 23 nt, 35 miRNAs of 22 nt and three miRNAs of 21 nt. On the other hand, the 3p strands lengths observed are: seven miRNAs of 23 nt, 50 miRNAs of 22 nt, six miRNAs of 21 nt and four miRNAs of 20 nt. Based on the analysis of the 20 miRNA families associated with cervical cancer, 67 3p strands and 65 5p strands are selected suggesting selectivity and specificity mechanisms regulating cell processes like proliferation, apoptosis, migration, invasion, metabolism and Warburg effect. The insight reviewed here could be used in the miRNA based therapy, diagnosis and prognosis approaches. PMID:28216603

  4. ImmunemiR - a database of prioritized immune miRNA disease associations and its interactome.

    PubMed

    Prabahar, Archana; Natarajan, Jeyakumar

    2017-01-17

    MicroRNAs are the key regulators of gene expression and their abnormal expression in the immune system may be associated with several human diseases such as inflammation, cancer and autoimmune diseases. Elucidation of microRNA (miRNA) disease association through the interactome will deepen the understanding of its disease mechanisms. In this present study, miRNAs specific to immune related diseases were retrieved from curated databases and literature based on MeSH classification of immune system diseases. In total 245 immune miRNAs associated with 92 OMIM disease categories were identified and they are prioritized to specific immune diseases using random walk ranking algorithm. These data were compiled as ImmunemiR, a database of prioritized immune miRNA disease associations. This database provides both text based annotation information and network visualization of its interactome network. To our knowledge, ImmunemiR is the first available database to provide a comprehensive repository of human immune disease associated miRNAs with network visualization options of its target genes, protein-protein interactions (PPI).

  5. Urinary chromium is associated with changes in leukocyte miRNA expression in obese subjects

    PubMed Central

    Dioni, L; Sucato, S; Motta, V; Iodice, S; Angelici, L; Favero, C; Cavalleri, T; Vigna, L; Albetti, B; Fustinoni, S; Bertazzi, P; Pesatori, A; Bollati, V

    2017-01-01

    Background/Objectives: Epidemiological studies suggest a link between chromium (Cr) status and cardiovascular disease. Increased urinary excretion of Cr was reported in subjects with diabetes compared with non-diabetic controls and those with non-diabetic insulin resistance. Epigenetic alterations have been linked to the presence of Cr, and microRNA (miRNA) expression has been implicated in the pathogenesis of metabolic diseases and cardiovascular diseases (CVDs). We investigated the association between Cr excretion and miRNA expression in leukocytes from obese subjects. We also examined the relationship between altered miRNA expression and selected clinical parameters to further investigate mechanisms linking Cr to metabolic diseases and CVDs. Subjects/Methods: We analyzed urinary Cr in 90 Italian subjects using inductively coupled plasma-mass spectrometry. Peripheral blood miRNA levels were screened with TaqMan Low-Density Array Human MicroRNA A. Cr level-associated expression of miRNAs was detected with multivariate regression analyses, and the top 10 candidate miRNAs were selected for validation. We also used multivariate regression analyses to assess possible associations between validated miRNAs and glycated hemoglobin (A1c) and blood pressure (BP). The validated miRNAs were further investigated by functional analysis with Ingenuity Pathway Analysis software. Results: Urinary Cr levels (mean: 0.35 μg/l; s.d.=0.24) ranged from 0.05 to 1.27 μg/l. In the screening phase, 43 miRNAs were negatively associated with Cr. Of the top 10 miRNAs selected for validation, nine (miR-451, miR-301, miR-15b, miR-21, miR-26a, miR-362-3p, miR-182, miR-183 and miR-486-3p) were downregulated in association with Cr (P-false discovery rate (FDR)<0.10). miR-451 expression was associated with A1c (β=–0.06; P=0.0416), whereas miR-486-3p expression was associated both with diastolic (β=2.1; P=0.004) and systolic BP (β=3.3; P=0.003). Conclusions: These results indicate that mi

  6. Reflections on Software Agility and Agile Methods: Challenges, Dilemmas, & the Way Ahead

    DTIC Science & Technology

    2005-05-11

    Mellon University 10 Research Team Richard Baskerville and Balasubramanian Ramesh Department of Computer Information Systems, Georgia State University...University 38 References Agile Manifesto. http://agilemanifesto.org/ Baskerville , R., Pries-Heje, J., Levine, L., & Ramesh, B. (2005). The high speed...balancing game: How software companies cope with Internet speed. Scandinavian Journal of Information Systems 16, 11-54. Baskerville , R., Levine, L

  7. RNA Binding Proteins in the miRNA Pathway.

    PubMed

    Connerty, Patrick; Ahadi, Alireza; Hutvagner, Gyorgy

    2015-12-26

    microRNAs (miRNAs) are short ~22 nucleotides (nt) ribonucleic acids which post-transcriptionally regulate gene expression. miRNAs are key regulators of all cellular processes, and the correct expression of miRNAs in an organism is crucial for proper development and cellular function. As a result, the miRNA biogenesis pathway is highly regulated. In this review, we outline the basic steps of miRNA biogenesis and miRNA mediated gene regulation focusing on the role of RNA binding proteins (RBPs). We also describe multiple mechanisms that regulate the canonical miRNA pathway, which depends on a wide range of RBPs. Moreover, we hypothesise that the interaction between miRNA regulation and RBPs is potentially more widespread based on the analysis of available high-throughput datasets.

  8. miRNA as molecular target of polyphenols underlying their biological effects.

    PubMed

    Milenkovic, Dragan; Jude, Baptiste; Morand, Christine

    2013-09-01

    Polyphenols are the most abundant antioxidants in the human diet and are widespread constituents of fruits and beverages, such as tea, coffee, and wine. Epidemiological, clinical, and animal studies support a role of polyphenols in the prevention of various chronic diseases. For a long time, their direct antioxidant effect has been reported as the mechanism responsible for the observed health properties. However, recent findings revealed that polyphenols could interact with cellular signaling cascades regulating the activity of transcription factors and consequently affecting the expression of genes. Together with this classical regulatory pathway, polyphenols have been shown to affect the expression of microRNAs (miRNA). miRNAs are small, noncoding RNAs implicated in the regulation of gene expression that control both physiological and pathological processes such as development and cancer. Furthermore, expression of miRNAs can be affected by different external stimuli including nutrients such as vitamins, lipids, and phytochemicals. In this paper, we review studies assessing modulation of miRNAs expression by dietary polyphenols that could constitute a new pathway by which these compounds may exert their health effects. Over 100 miRNAs, involved in the control of different cellular processes such as inflammation or apoptosis, were identified as modulated by polyphenols. Most of the studies were performed in vitro using different cell lines, particularly cancer cell lines, and few studies were performed in animals. From all these data, miRNAs appear as interesting mediators in regulating polyphenols' biological effects; however, further studies are needed to validate miRNA targets and particularly in physiologically relevant conditions taking into account the bioavailability of dietary polyphenols.

  9. Virus-Mediated Alterations in miRNA Factors and Degradation of Viral miRNAs by MCPIP1

    PubMed Central

    Happel, Christine; Ramalingam, Dhivya; Ziegelbauer, Joseph M.

    2016-01-01

    Kaposi’s sarcoma-associated herpesvirus (KSHV), the causative agent of Kaposi’s sarcoma, encodes 25 mature viral miRNAs. MCP-1-induced protein-1 (MCPIP1), a critical regulator of immune homeostasis, has been shown to suppress miRNA biosynthesis via cleavage of precursor miRNAs through its RNase domain. We demonstrate that MCPIP1 can directly cleave KSHV and EBV precursor miRNAs and that MCPIP1 expression is repressed following de novo KSHV infection. In addition, repression with siRNAs to MCPIP1 in KSHV-infected cells increased IL-6 and KSHV miRNA expression, supporting a role for MCPIP1 in IL-6 and KSHV miRNA regulation. We also provide evidence that KSHV miRNAs repress MCPIP1 expression by targeting the 3’UTR of MCPIP1. Conversely, expression of essential miRNA biogenesis components Dicer and TRBP is increased following latent KSHV infection. We propose that KSHV infection inhibits a negative regulator of miRNA biogenesis (MCPIP1) and up-regulates critical miRNA processing components to evade host mechanisms that inhibit expression of viral miRNAs. KSHV-mediated alterations in miRNA biogenesis represent a novel mechanism by which KSHV interacts with its host and a new mechanism for the regulation of viral miRNA expression. PMID:27893764

  10. Discovery of miRNAs and Their Corresponding miRNA Genes in Atlantic Cod (Gadus morhua): Use of Stable miRNAs as Reference Genes Reveals Subgroups of miRNAs That Are Highly Expressed in Particular Organs

    PubMed Central

    Andreassen, Rune; Rangnes, Fredrik; Sivertsen, Maria; Chiang, Michelle; Tran, Michelle; Worren, Merete Molton

    2016-01-01

    Background Atlantic cod (Gadus morhua) is among the economically most important species in the northern Atlantic Ocean and a model species for studying development of the immune system in vertebrates. MicroRNAs (miRNAs) are an abundant class of small RNA molecules that regulate fundamental biological processes at the post-transcriptional level. Detailed knowledge about a species miRNA repertoire is necessary to study how the miRNA transcriptome modulate gene expression. We have therefore discovered and characterized mature miRNAs and their corresponding miRNA genes in Atlantic cod. We have also performed a validation study to identify suitable reference genes for RT-qPCR analysis of miRNA expression in Atlantic cod. Finally, we utilized the newly characterized miRNA repertoire and the dedicated RT-qPCR method to reveal miRNAs that are highly expressed in certain organs. Results The discovery analysis revealed 490 mature miRNAs (401 unique sequences) along with precursor sequences and genomic location of the miRNA genes. Twenty six of these were novel miRNA genes. Validation studies ranked gmo-miR-17-1—5p or the two-gene combination gmo-miR25-3p and gmo-miR210-5p as most suitable qPCR reference genes. Analysis by RT-qPCR revealed 45 miRNAs with significantly higher expression in tissues from one or a few organs. Comparisons to other vertebrates indicate that some of these miRNAs may regulate processes like growth, lipid metabolism, immune response to microbial infections and scar damage repair. Three teleost-specific and three novel Atlantic cod miRNAs were among the differentially expressed miRNAs. Conclusions The number of known mature miRNAs was considerably increased by our identification of miRNAs and miRNA genes in Atlantic cod. This will benefit further functional studies of miRNA expression using deep sequencing methods. The validation study showed that stable miRNAs are suitable reference genes for RT-qPCR analysis of miRNA expression. Applying RT-qPCR we

  11. Compact, flexible, frequency agile parametric wavelength converter

    DOEpatents

    Velsko, Stephan P.; Yang, Steven T.

    2002-01-01

    This improved Frequency Agile Optical Parametric Oscillator provides near on-axis pumping of a single QPMC with a tilted periodically poled grating to overcome the necessity to find a particular crystal that will permit collinear birefringence in order to obtain a desired tuning range. A tilted grating design and the elongation of the transverse profile of the pump beam in the angle tuning plane of the FA-OPO reduces the rate of change of the overlap between the pumped volume in the crystal and the resonated and non-resonated wave mode volumes as the pump beam angle is changed. A folded mirror set relays the pivot point for beam steering from a beam deflector to the center of the FA-OPO crystal. This reduces the footprint of the device by as much as a factor of two over that obtained when using the refractive telescope design.

  12. Agile: From Software to Mission System

    NASA Technical Reports Server (NTRS)

    Trimble, Jay; Shirley, Mark H.; Hobart, Sarah Groves

    2016-01-01

    The Resource Prospector (RP) is an in-situ resource utilization (ISRU) technology demonstration mission, designed to search for volatiles at the Lunar South Pole. This is NASA's first near real time tele-operated rover on the Moon. The primary objective is to search for volatiles at one of the Lunar Poles. The combination of short mission duration, a solar powered rover, and the requirement to explore shadowed regions makes for an operationally challenging mission. To maximize efficiency and flexibility in Mission System design and thus to improve the performance and reliability of the resulting Mission System, we are tailoring Agile principles that we have used effectively in ground data system software development and applying those principles to the design of elements of the mission operations system.

  13. Fast and Simplified Method for High Through-put Isolation of miRNA from Highly Purified High Density Lipoprotein

    PubMed Central

    Seneshaw, Mulugeta; Mirshahi, Faridoddin; Min, Hae-Ki; Asgharpour, Amon; Mirshahi, Shervin; Daita, Kalyani; Boyett, Sherry; Santhekadur, Prasanna K.; Fuchs, Michael; Sanyal, Arun J.

    2016-01-01

    Small non-coding RNAs (miRNAs) have been implicated in a variety of human diseases including metabolic syndromes. They may be utilized as biomarkers for diagnosis and prognosis or may serve as targets for drug development, respectively. Recently it has been shown that miRNAs are carried in lipoproteins, particularly high density lipoproteins (HDL) and are delivered to recipient cells for uptake. This raises the possibility that miRNAs play a critical and pivotal role in cellular and organ function via regulation of gene expression as well as messenger for cell-cell communications and crosstalk between organs. Current methods for miRNA isolation from purified HDL are impractical when utilizing small samples on a large scale. This is largely due to the time consuming and laborious methods used for lipoprotein isolation. We have developed a simplified approach to rapidly isolate purified HDL suitable for miRNA analysis from plasma samples. This method should facilitate investigations into the role of miRNAs in health and disease and in particular provide new insights into the variety of biological functions, outside of the reverse cholesterol transport, that have been ascribed to HDL. Also, the miRNA species which are present in HDL can provide valuable information of clinical biomarkers for diagnosis of various diseases. PMID:27501005

  14. Moving target detection for frequency agility radar by sparse reconstruction.

    PubMed

    Quan, Yinghui; Li, YaChao; Wu, Yaojun; Ran, Lei; Xing, Mengdao; Liu, Mengqi

    2016-09-01

    Frequency agility radar, with randomly varied carrier frequency from pulse to pulse, exhibits superior performance compared to the conventional fixed carrier frequency pulse-Doppler radar against the electromagnetic interference. A novel moving target detection (MTD) method is proposed for the estimation of the target's velocity of frequency agility radar based on pulses within a coherent processing interval by using sparse reconstruction. Hardware implementation of orthogonal matching pursuit algorithm is executed on Xilinx Virtex-7 Field Programmable Gata Array (FPGA) to perform sparse optimization. Finally, a series of experiments are performed to evaluate the performance of proposed MTD method for frequency agility radar systems.

  15. Moving target detection for frequency agility radar by sparse reconstruction

    NASA Astrophysics Data System (ADS)

    Quan, Yinghui; Li, YaChao; Wu, Yaojun; Ran, Lei; Xing, Mengdao; Liu, Mengqi

    2016-09-01

    Frequency agility radar, with randomly varied carrier frequency from pulse to pulse, exhibits superior performance compared to the conventional fixed carrier frequency pulse-Doppler radar against the electromagnetic interference. A novel moving target detection (MTD) method is proposed for the estimation of the target's velocity of frequency agility radar based on pulses within a coherent processing interval by using sparse reconstruction. Hardware implementation of orthogonal matching pursuit algorithm is executed on Xilinx Virtex-7 Field Programmable Gata Array (FPGA) to perform sparse optimization. Finally, a series of experiments are performed to evaluate the performance of proposed MTD method for frequency agility radar systems.

  16. Agile rediscovering values: Similarities to continuous improvement strategies

    NASA Astrophysics Data System (ADS)

    Díaz de Mera, P.; Arenas, J. M.; González, C.

    2012-04-01

    Research in the late 80's on technological companies that develop products of high value innovation, with sufficient speed and flexibility to adapt quickly to changing market conditions, gave rise to the new set of methodologies known as Agile Management Approach. In the current changing economic scenario, we considered very interesting to study the similarities of these Agile Methodologies with other practices whose effectiveness has been amply demonstrated in both the West and Japan. Strategies such as Kaizen, Lean, World Class Manufacturing, Concurrent Engineering, etc, would be analyzed to check the values they have in common with the Agile Approach.

  17. Exosomes as miRNA Carriers: Formation-Function-Future.

    PubMed

    Yu, Xiaojie; Odenthal, Margarete; Fries, Jochen W U

    2016-12-02

    Exosomes, which are one of the smallest extracellular vesicles released from cells, have been shown to carry different nucleic acids, including microRNAs (miRNAs). miRNAs significantly regulate cell growth and metabolism by posttranscriptional inhibition of gene expression. The rapidly changing understanding of exosomes' formation and function in delivering miRNAs from cell to cell has prompted us to review current knowledge in exosomal miRNA secretion mechanisms as well as possible therapeutic applications for personalized medicine.

  18. Agile parallel bioinformatics workflow management using Pwrake

    PubMed Central

    2011-01-01

    Background In bioinformatics projects, scientific workflow systems are widely used to manage computational procedures. Full-featured workflow systems have been proposed to fulfil the demand for workflow management. However, such systems tend to be over-weighted for actual bioinformatics practices. We realize that quick deployment of cutting-edge software implementing advanced algorithms and data formats, and continuous adaptation to changes in computational resources and the environment are often prioritized in scientific workflow management. These features have a greater affinity with the agile software development method through iterative development phases after trial and error. Here, we show the application of a scientific workflow system Pwrake to bioinformatics workflows. Pwrake is a parallel workflow extension of Ruby's standard build tool Rake, the flexibility of which has been demonstrated in the astronomy domain. Therefore, we hypothesize that Pwrake also has advantages in actual bioinformatics workflows. Findings We implemented the Pwrake workflows to process next generation sequencing data using the Genomic Analysis Toolkit (GATK) and Dindel. GATK and Dindel workflows are typical examples of sequential and parallel workflows, respectively. We found that in practice, actual scientific workflow development iterates over two phases, the workflow definition phase and the parameter adjustment phase. We introduced separate workflow definitions to help focus on each of the two developmental phases, as well as helper methods to simplify the descriptions. This approach increased iterative development efficiency. Moreover, we implemented combined workflows to demonstrate modularity of the GATK and Dindel workflows. Conclusions Pwrake enables agile management of scientific workflows in the bioinformatics domain. The internal domain specific language design built on Ruby gives the flexibility of rakefiles for writing scientific workflows. Furthermore, readability

  19. Comparative analysis of EV isolation procedures for miRNAs detection in serum samples

    PubMed Central

    Andreu, Zoraida; Rivas, Eva; Sanguino-Pascual, Aitana; Lamana, Amalia; Marazuela, Mónica; González-Alvaro, Isidoro; Sánchez-Madrid, Francisco; de la Fuente, Hortensia; Yáñez-Mó, María

    2016-01-01

    Extracellular vesicles (EVs) are emerging as potent non-invasive biomarkers. However, current methodologies are time consuming and difficult to translate to clinical practice. To analyse EV-encapsulated circulating miRNA, we searched for a quick, easy and economic method to enrich frozen human serum samples for EV. We compared the efficiency of several protocols and commercial kits to isolate EVs. Different methods based on precipitation, columns or filter systems were tested and compared with ultracentrifugation, which is the most classical protocol to isolate EVs. EV samples were assessed for purity and quantity by nanoparticle tracking analysis and western blot or cytometry against major EV protein markers. For biomarker validation, levels of a set of miRNAs were determined in EV fractions and compared with their levels in total serum. EVs isolated with precipitation-based methods were enriched for a subgroup of miRNAs that corresponded to miRNAs described to be encapsulated into EVs (miR-126, miR-30c and miR-143), while the detection of miR-21, miR-16-5p and miR-19a was very low compared with total serum. Our results point to precipitation using polyethylene glycol (PEG) as a suitable method for an easy and cheap enrichment of serum EVs for miRNA analyses. The overall performance of PEG was very similar, or better than other commercial precipitating reagents, in both protein and miRNA yield, but in comparison to them PEG is much cheaper. Other methods presented poorer results, mostly when assessing miRNA by qPCR analyses. Using PEG precipitation in a longitudinal study with human samples, we demonstrated that miRNA could be assessed in frozen samples up to 8 years of storage. We report a method based on a cut-off value of mean of fold EV detection versus serum that provides an estimate of the degree of encapsulation of a given miRNA. PMID:27330048

  20. miRNA-149* promotes cell proliferation and suppresses apoptosis by mediating JunB in T-cell acute lymphoblastic leukemia.

    PubMed

    Fan, Sheng-Jin; Li, Hui-Bo; Cui, Gang; Kong, Xiao-Lin; Sun, Li-Li; Zhao, Yan-Qiu; Li, Ying-Hua; Zhou, Jin

    2016-02-01

    MicroRNA-149* (miRNA-149*) functions as an oncogenic regulator in human melanoma. However, the effect of miRNA-149* on T-cell acute lymphoblastic leukemia (T-ALL) is unclear. Here we aimed to analyze the effects of miRNA-149* on in vitro T-ALL cells and to uncover the target for miRNA-149* in these cells. The miRNA-149* level was determined in multiple cell lines and bone marrow cells derived from patients with T-ALL, B acute lymphoblastic leukemia (B-ALL), acute myelocytic leukemia (AML), and healthy donors. We found that miRNA-149* was highly expressed in T-ALL cell lines and T-ALL patients' bone marrow samples. JunB was identified as a direct target of miR-149*. miRNA-149* mimics downregulated JunB levels in Molt-4 and Jurkat cells, while miRNA-149* inhibitors dramatically upregulated JunB expression in these cells. miRNA-149* mimics promoted proliferation, decreased the proportion of cells in G1 phase, and reduced cell apoptosis in T-ALL cells, while miRNA-149* inhibitors prevented these effects. miRNA-149* mimics downregulated p21 and upregulated cyclinD1, 4EBP1, and p70s6k in Molt-4 and Jurkat cells. Again, inhibitors prevented these effects. Our findings demonstrate that miRNA-149* may serve as an oncogenic regulator in T-ALL by negatively regulating JunB.

  1. A myriad of miRNA variants in control and Huntington’s disease brain regions detected by massively parallel sequencing

    PubMed Central

    Martí, Eulàlia; Pantano, Lorena; Bañez-Coronel, Mónica; Llorens, Franc; Miñones-Moyano, Elena; Porta, Sílvia; Sumoy, Lauro; Ferrer, Isidre; Estivill, Xavier

    2010-01-01

    Huntington disease (HD) is a neurodegenerative disorder that predominantly affects neurons of the forebrain. We have applied the Illumina massively parallel sequencing to deeply analyze the small RNA populations of two different forebrain areas, the frontal cortex (FC) and the striatum (ST) of healthy individuals and individuals with HD. More than 80% of the small-RNAs were annotated as microRNAs (miRNAs) in all samples. Deep sequencing revealed length and sequence heterogeneity (IsomiRs) for the vast majority of miRNAs. Around 80–90% of the miRNAs presented modifications in the 3′-terminus mainly in the form of trimming and/or as nucleotide addition variants, while the 5′-terminus of the miRNAs was specially protected from changes. Expression profiling showed strong miRNA and isomiR expression deregulation in HD, most being common to both FC and ST. The analysis of the upstream regulatory regions in co-regulated miRNAs suggests a role for RE1-Silencing Transcription Factor (REST) and P53 in miRNAs downregulation in HD. The putative targets of deregulated miRNAs and seed-region IsomiRs strongly suggest that their altered expression contributes to the aberrant gene expression in HD. Our results show that miRNA variability is a ubiquitous phenomenon in the adult human brain, which may influence gene expression in physiological and pathological conditions. PMID:20591823

  2. GRB 070724B: the first Gamma Ray Burst localized by SuperAGILE

    SciTech Connect

    Del Monte, E.; Costa, E.; Donnarumma, I.; Feroci, M.; Lapshov, I.; Lazzarotto, F.; Soffitta, P.; Argan, A.; Pucella, G.; Trois, A.; Vittorini, V.; Evangelista, Y.; Rapisarda, M.; Barbiellini, G.; Longo, F.; Basset, M.; Foggetta, L.; Vallazza, E.; Bulgarelli, A.; Di Cocco, G.

    2008-05-22

    GRB070724B is the first Gamma Ray Burst localized by the SuperAGILE instrument aboard the AGILE space mission. The SuperAGILE localization has been confirmed after the after-glow observation by the XRT aboard the Swift satellite. No significant gamma ray emission above 50 MeV has been detected for this GRB. In this paper we describe the SuperAGILE capabilities in detecting Gamma Ray Burst and the AGILE observation of GRB 070724B.

  3. Characterization of miRNAs involved in response to poly(I:C) in porcine airway epithelial cells.

    PubMed

    Wang, L; Wang, J K; Han, L X; Zhuo, J S; Du, X; Liu, D; Yang, X Q

    2017-04-01

    MicroRNAs (miRNA) have been implicated in a variety of pathological conditions including infectious diseases. Knowledge of the miRNAs affected by poly(I:C), a synthetic analog of viral double-stranded RNA, in porcine airway epithelial cells (PAECs) contributes to understanding the mechanisms of swine viral respiratory diseases, which bring enormous economic loss worldwide every year. In this study, we used high throughput sequencing to profile miRNA expression in PAECs treated with poly(I:C) as compared to the untreated control. This approach revealed 23 differentially expressed miRNAs (DEMs), five of which have not been implicated in viral infection before. Nineteen of the 23 miRNAs were down-regulated including members of the miR-17-92 cluster, a well-known polycistronic oncomir and extensively involved in viral infection in humans. Target genes of DEMs, predicted using bioinformatic methods and validated by luciferase reporter analysis on two representative DEMs, were significantly enriched in several pathways including transforming growth factor-β signaling. A large quantity of sequence variations (isomiRs) were found including a substitution at position 5, which was verified to redirect miRNAs to a new spectrum of targets by luciferase reporter assay together with bioinformatics analysis. Twelve novel porcine miRNAs conserved in other species were identified by homology analysis together with cloning verification. Furthermore, the expression analysis revealed the potential importance of three novel miRNAs in porcine immune response to viruses. Overall, our data contribute to clarifying the mechanisms underlying the host immune response against respiratory viruses in pigs, and enriches the repertoire of porcine miRNAs.

  4. High-Throughput Sequencing Reveals Circulating miRNAs as Potential Biomarkers for Measuring Puberty Onset in Chicken (Gallus gallus)

    PubMed Central

    Su, Yijun; Li, Guohui; Qu, Liang; Zhang, Huiyong; Wang, Kehua; Zou, Jianmin; Liu, Honglin

    2016-01-01

    There are still no highly sensitive and unique biomarkers for measurement of puberty onset. Circulating miRNAs have been shown to be promising biomarkers for diagnosis of various diseases. To identify circulating miRNAs that could be served as biomarkers for measuring chicken (Gallus gallus) puberty onset, the Solexa deep sequencing was performed to analyze the miRNA expression profiles in serum and plasma of hens from two different pubertal stages, before puberty onset (BO) and after puberty onset (AO). 197 conserved and 19 novel miRNAs (reads > 10) were identified as serum/plasma-expressed miRNAs in the chicken. The common miRNA amounts and their expression changes from BO to AO between serum and plasma were very similar, indicating the different treatments to generate serum and plasma had quite small influence on the miRNAs. 130 conserved serum-miRNAs were showed to be differentially expressed (reads > 10, P < 0.05) from BO to AO, with 68 up-regulated and 62 down-regulated. 4829 putative genes were predicted as the targets of the 40 most differentially expressed miRNAs (|log2(fold-change)|>1.0, P < 0.01). Functional analysis revealed several pathways that were associated with puberty onset. Further quantitative real-time PCR (RT-qPCR) test found that a seven-miRNA panel, including miR-29c, miR-375, miR-215, miR-217, miR-19b, miR-133a and let-7a, had great potentials to serve as novel biomarkers for measuring puberty onset in chicken. Due to highly conserved nature of miRNAs, the findings could provide cues for measurement of puberty onset in other animals as well as humans. PMID:27149515

  5. Spatial Partitioning of miRNAs Is Related to Sequence Similarity in Overall Transcriptome

    PubMed Central

    Seffens, William; Abebe, Fisseha; Evans, Chad; Wang, Xiao-Qian

    2016-01-01

    RNAs have been shown to exhibit differential enrichment between nuclear, cytoplasmic, and exosome fractions. A current fundamental question asks why non-coding RNA partition into different spatial compartments. We report on the analysis of cellular compartment models with miRNA data sources for spatial-mechanistic modeling to address the broad area of multi-scalar cellular communication by miRNAs. We show that spatial partitioning of miRNAs is related to sequence similarity to the overall transcriptome. This has broad implications in biological informatics for gene regulation and provides a deeper understanding of nucleotide sequence structure and RNA language meaning for human pathologies resulting from changes in gene expression. PMID:27338352

  6. MiRNA need a TRIM regulation of miRNA activity by Trim-NHL proteins.

    PubMed

    Wulczyn, F Gregory; Cuevas, Elisa; Franzoni, Eleonora; Rybak, Agnieszka

    2010-01-01

    Trim-NHL proteins are defined by RING, B-Box and Coiled-coil protein motifs (referred to collectively as the Trim domain) coupled to an NHL domain. The C. elegans, D. melanogaster, mouse and human Trim-NHL proteins are potential and in several cases confirmed, E3 ubiquitin ligases. Current research is focused on identifying targets and pathways for Trim-NHL-mediated ubiquitination and in assessing the contribution of the NHL protein-protein interactiondomain for function and specificity. Several Trim-NHL proteins were discovered in screens for developmental genes in model organisms; mutations in one of the family members, Trim32, cause developmental disturbances in humans. In most instances, mutations that alter protein function map to the NHL domain. The NHL domain is a scaffold for the assembly of a translational repressor complex by the Brat proto-oncogene, a well-studied family member in Drosophila. The link to translational control is common to at least four Trim-NHLs that associate with miRNA pathway proteins. So far, two have been shown to repress (Mei-P26 and Lin41) and two to promote (NHL-2, Trim32) miRNA-mediated gene silencing. In this chapter we will describe structure-function relations for each of the proteins and then focus on the lessons being learned from these proteins about miRNA functions in development and in stem cell biology.

  7. miRNAs Need a Trim : Regulation of miRNA Activity by Trim-NHL Proteins.

    PubMed

    Wulczyn, F Gregory; Cuevas, Elisa; Franzoni, Eleonora; Rybak, Agnieszka

    2011-01-01

    Trim-NHL proteins are defined by RING, B-Box and Coiled-coil protein motifs (referred to collectively as the Trim domain) coupled to an NHL domain. The C. elegans, D. melanogaster, mouse and human Trim-NHL proteins are potential and in several cases confirmed, E3 ubiquitin ligases. Current research is focused on identifying targets and pathways for Trim-NHL-mediated ubiquitination and in assessing the contribution of the NHL protein-protein interaction domain for function and specificity. Several Trim-NHL proteins were discovered in screens for developmental genes in model organisms; mutations in one of the family members, Trim32, cause developmental disturbances in humans. In most instances, mutations that alter protein function map to the NHL domain. The NHL domain is a scaffold for the assembly of a translational repressor complex by the Brat proto-oncogene, a well-studied family member in Drosophila. The link to translational control is common to at least four Trim-NHLs that associate with miRNA pathway proteins. So far, two have been shown to repress (Mei-P26 and Lin41) and two to promote (NHL-2, Trim32) miRNA-mediated gene silencing. In this chapter we will describe structure-function relations for each of the proteins and then focus on the lessons being learned from these proteins about miRNA functions in development and in stem cell biology.

  8. Value Creation by Agile Projects: Methodology or Mystery?

    NASA Astrophysics Data System (ADS)

    Racheva, Zornitza; Daneva, Maya; Sikkel, Klaas

    Business value is a key concept in agile software development approaches. This paper presents results of a systematic review of literature on how business value is created by agile projects. We found that with very few exceptions, most published studies take the concept of business value for granted and do not state what it means in general as well as in the specific study context. We could find no study which clearly indicates how exactly individual agile practices or groups of those create value and keep accumulating it over time. The key implication for research is that we have an incentive to pursue the study of value creation in agile project by deploying empirical research methods.

  9. Laterality and performance of agility-trained dogs.

    PubMed

    Siniscalchi, Marcello; Bertino, Daniele; Quaranta, Angelo

    2014-01-01

    Correlations between lateralised behaviour and performance were investigated in 19 agility-trained dogs (Canis familiaris) by scoring paw preference to hold a food object and relating it to performance during typical agility obstacles (jump/A-frame and weave poles). In addition, because recent behavioural studies reported that visual stimuli of emotional valence presented to one visual hemifield at a time affect visually guided motor responses in dogs, the possibility that the position of the owner respectively in the left and in the right canine visual hemifield might be associated with quality of performance during agility was considered. Dogs' temperament was also measured by an owner-rated questionnaire. The most relevant finding was that agility-trained dogs displayed longer latencies to complete the obstacles with the owner located in their left visual hemifield compared to the right. Interestingly, the results showed that this phenomenon was significantly linked to both dogs' trainability and the strength of paw preference.

  10. Frequency agile OPO-based transmitters for multiwavelength DIAL

    SciTech Connect

    Velsko, S.P.; Ruggiero, A.; Herman, M.

    1996-09-01

    We describe a first generation mid-infrared transmitter with pulse-to- pulse frequency agility and both wide and narrow band capability. This transmitter was used to make multicomponent DIAL measurements in the field.

  11. Investigation into the impact of agility on conceptual fighter design

    NASA Technical Reports Server (NTRS)

    Engelbeck, R. M.

    1995-01-01

    The Agility Design Study was performed by the Boeing Defense and Space Group for the NASA Langley Research Center. The objective of the study was to assess the impact of agility requirements on new fighter configurations. Global trade issues investigated were the level of agility, the mission role of the aircraft (air-to-ground, multi-role, or air-to-air), and whether the customer is Air force, Navy, or joint service. Mission profiles and design objectives were supplied by NASA. An extensive technology assessment was conducted to establish the available technologies to industry for the aircraft. Conceptual level methodology is presented to assess the five NASA-supplied agility metrics. Twelve configurations were developed to address the global trade issues. Three-view drawings, inboard profiles, and performance estimates were made and are included in the report. A critical assessment and lessons learned from the study are also presented.

  12. Pilot users in agile development processes: motivational factors.

    PubMed

    Johannessen, Liv Karen; Gammon, Deede

    2010-01-01

    Despite a wealth of research on user participation, few studies offer insights into how to involve multi-organizational users in agile development methods. This paper is a case study of user involvement in developing a system for electronic laboratory requisitions using agile methodologies in a multi-organizational context. Building on an interpretive approach, we illuminate questions such as: How does collaboration between users and developers evolve and how might it be improved? What key motivational aspects are at play when users volunteer and continue contributing in the face of considerable added burdens? The study highlights how agile methods in themselves appear to facilitate mutually motivating collaboration between user groups and developers. Lessons learned for leveraging the advantages of agile development processes include acknowledging the substantial and ongoing contributions of users and their roles as co-designers of the system.

  13. Frequency agile OPO-based transmitters for multiwavelength DIAL

    SciTech Connect

    Velsko, S.P.; Ruggiero, A.; Herman, M.

    1996-09-01

    We describe a first generation mid-infrared transmitter with pulse to pulse frequency agility and both wide and narrow band capability. This transmitter was used to make multicomponent Differential Absorption LIDAR (DIAL) measurements in the field.

  14. Modern Enterprise Systems as Enablers of Agile Development

    NASA Astrophysics Data System (ADS)

    Fredriksson, Odd; Ljung, Lennart

    Traditional ES technology and traditional project management methods are supporting and matching each other. But they are not supporting the critical success conditions for ES development in an effective way. Although the findings from one case study of a successful modern ES change project is not strong empirical evidence, we carefully propose that the new modern ES technology is supporting and matching agile project management methods. In other words, it provides the required flexibility which makes it possible to put into practice the agile way of running projects, both for the system supplier and for the customer. In addition, we propose that the combination of modern ES technology and agile project management methods are more appropriate for supporting the realization of critical success conditions for ES development. The main purpose of this chapter is to compare critical success conditions for modern enterprise systems development projects with critical success conditions for agile information systems development projects.

  15. Agile Software Development in Defense Acquisition: A Mission Assurance Perspective

    DTIC Science & Technology

    2012-03-23

    AEROSPACE REPORT NO ATR -2012(9010)-2 Agile Software Development in Defense Acquisition - A Mission Assurance Perspective March 23, 2012 Peter...release; distribution unlimited. aoUc£23>o;r7 AEROSPACE REPORT NO ATR -2012(9010)-2 Agile Software Development in Defense Acquisition - A Mission...Engineering and Technology Group Approved for public release; distribution unlimited. (A\\ AEROSPACE ^•^ Aautoff $m MK*I? taH AEROSPACE REPORT NO ATR

  16. Coaching for Better (Software) Buying Power in an Agile World

    DTIC Science & Technology

    2013-06-01

    professionals carefully to consider incorporation of agile methodologies into the set of acquisition tools at their disposal. This transformation is not...believes that DevOps , the process of warfighters and developers work- ing together throughout the project, is superior to volumes of detailed...Professionalism of the Total Acquisition Workforce The DoD needs to invest in training the acquisition workforce in agile methodologies to add tools that

  17. Spectroscopic Investigation of Materials for Frequency Agile Laser Systems.

    DTIC Science & Technology

    1985-01-01

    fluorescence spectra and lifetimes of divalent Rh, Ru, Pt, and Ir ions in alkali halide crystals are measured using pulsed nitrogen laser excitation...AD-Ai5t 73t SPECTROSCOPIC INVESTIGRTION OF MATERIALS FOR FREQUENCY t/ AGILE LASER SYSTEMS(U) OKLAHOMA STATE UNIV STILLWATER DEPT OF PHYSICS R C...INVESTIGATION OF MATERIALS FOR FREQUENCY AGILE LASER SYSTEMS Richard C. Powell, Ph.D. Principal Investigator Department of Physics OKLAHOMA STATE UNIVERSITY

  18. Addressing the Barriers to Agile Development in DoD

    DTIC Science & Technology

    2015-05-01

    acquisition development  IT programs are subject to extensive documentation, reviews, and oversight that inhibits speed and agility needed for IT  Major...Based on Program, Ops, and Technical Risk Structuring an Agile Program  Notional: 6 Month Release with 4-Week Sprints – Continual development...integration, and testing – Monthly demonstration of capabilities to users  Gov’t testers, certifiers, and users involved early and often – Minimizes

  19. Architectural Tactics to Support Rapid and Agile Stability

    DTIC Science & Technology

    2012-05-01

    20 CrossTalk—May/June 2012 RAPID AND AGILE STABILITY • Scrum teams, product development teams, component teams, or feature teams spend almost...and individuals in the roles of Scrum master, developer, project manager, and architect on projects from organizations that develop embedded real...agile stability. Using Scrum , 25 teams participated in the develop- ment effort. Some of the teams were colocated; teams (waste), while not evolving

  20. Identification, Characterization, and Evaluation Criteria for Systems Engineering Agile Enablers

    DTIC Science & Technology

    2015-01-16

    monitoring communications in social media groups and websites (such as LinkedIn or Facebook groups associated with the Scaled Agile Framework, Lean... Identification , Characterization, and Evaluation Criteria for Systems Engineering Agile Enablers Technical Report SERC-2015-TR-049-1...currently valid OMB control number 1. REPORT DATE 16 JAN 2015 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE Identification

  1. Need for Agility in Security Constraints for Distributed Simulation

    DTIC Science & Technology

    2014-06-01

    Submission to: 19th ICCRTS Title: Need for Agility in Security Constraints for Distributed Simulation (024) Topics: Primary Topic: 5...Modelling and Simulation , Alternates: 4. Experimentation, Metrics and Analysis, and 1. Concepts, Theory, and Policy S. K. Numrich, Ph.D...REPORT TYPE 3. DATES COVERED 00-00-2014 to 00-00-2014 4. TITLE AND SUBTITLE Need for Agility in Security Constraints for Distributed Simulation

  2. Light-Driven Chiral Molecular Motors for Passive Agile Filters

    DTIC Science & Technology

    2014-05-20

    AFRL-OSR-VA-TR-2014-0121 LIGHT-DRIVEN CHIRAL MOLECULAR MOTORS FOR PASSIVE AGILE FILTERS Quan Li KENT STATE UNIV OH Final Report 05/20/2014...Prescribed by ANSI Std. Z39.18 1 FINAL REPORT Title: Light-driven Chiral Molecular Motors for Passive Agile Filters AFOSR...As we proposed originally, the major objective of this project was to synthesize novel light- driven chiral molecular motors or switches targeted

  3. The impact of flying qualities on helicopter operational agility

    NASA Technical Reports Server (NTRS)

    Padfield, Gareth D.; Lappos, Nick; Hodgkinson, John

    1993-01-01

    Flying qualities standards are formally set to ensure safe flight and therefore reflect minimum, rather than optimum, requirements. Agility is a flying quality but relates to operations at high, if not maximum, performance. While the quality metrics and test procedures for flying, as covered for example in ADS33C, may provide an adequate structure to encompass agility, they do not currently address flight at high performance. This is also true in the fixed-wing world and a current concern in both communities is the absence of substantiated agility criteria and possible conflicts between flying qualities and high performance. AGARD is sponsoring a working group (WG19) title 'Operational Agility' that deals with these and a range of related issues. This paper is condensed from contributions by the three authors to WG19, relating to flying qualities. Novel perspectives on the subject are presented including the agility factor, that quantifies performance margins in flying qualities terms; a new parameter, based on maneuver acceleration is introduced as a potential candidate for defining upper limits to flying qualities. Finally, a probabilistic analysis of pilot handling qualities ratings is presented that suggests a powerful relationship between inherent airframe flying qualities and operational agility.

  4. MicroRNAs, macrocontrol: regulation of miRNA processing.

    PubMed

    Slezak-Prochazka, Izabella; Durmus, Selvi; Kroesen, Bart-Jan; van den Berg, Anke

    2010-06-01

    MicroRNAs (miRNAs) are a set of small, non-protein-coding RNAs that regulate gene expression at the post-transcriptional level. Maturation of miRNAs comprises several regulated steps resulting in approximately 22-nucleotide single-stranded mature miRNAs. Regulation of miRNA expression can occur both at the transcriptional level and at the post-transcriptional level during miRNA processing. Recent studies have elucidated specific aspects of the well-regulated nature of miRNA processing involving various regulatory proteins, editing of miRNA transcripts, and cellular location. In addition, single nucleotide polymorphisms in miRNA genes can also affect the processing efficiency of primary miRNA transcripts. In this review we present an overview of the currently known regulatory pathways of miRNA processing and provide a basis to understand how aberrant miRNA processing may arise and may be involved in pathophysiological conditions such as cancer.

  5. Mitochondria: one of the destinations of miRNAs.

    PubMed

    Sripada, Lakshmi; Tomar, Dhanendra; Singh, Rajesh

    2012-11-01

    The cellular processes are controlled by a narrow range of mRNA and proteins levels, where small RNAs (sRNAs) known as miRNAs play a critical role. The spatial and temporal regulation of miRNA processing components and mature miRNA is emerging. The recent studies suggest that mitochondria are one of the destinations of pre as well as mature miRNAs. The role of mitochondria extends beyond energy metabolism to many other cellular processes like metabolism, cell death and inflammation. The new found destination of miRNAs suggest the role of mitochondria in monitoring site specific regulations of proteins as well as the function of mitochondria. The studies in this direction will decipher the novel role of mitochondria-associated miRNAs in different cellular processes. This review is focussed on the recent studies demonstrating the presence of miRNAs in mitochondria and its possible significance in different cellular and physiological conditions.

  6. Increased expression of miRNA-146a in Alzheimer’s disease transgenic mouse models

    PubMed Central

    Li, Y.Y.; Cui, J.G.; Hill, J.M.; Bhattacharjee, S.; Zhao, Y.; Lukiw, W.J.

    2017-01-01

    A mouse and human brain-enriched micro-RNA-146a (miRNA-146a) is known to be important in modulating the innate immune response and inflammatory signaling in certain immunological and brain cell types. In this study we examined miRNA-146a levels in early-, moderate- and late-stage Alzheimer’s disease (AD) neocortex and hippocampus, in several human primary brain and retinal cell lines, and in 5 different transgenic mouse models of AD including Tg2576, TgCRND8, PSAPP, 3xTg-AD and 5xFAD. Inducible expression of miRNA-146a was found to be significantly up-regulated in a primary co-culture of human neuronal–glial (HNG) cells stressed using interleukin1-beta (IL-1β), and this up-regulation was quenched using specific NF-κB inhibitors including curcumin. Expression of miRNA-146a correlated with senile plaque density and synaptic pathology in Tg2576 and in 5xFAD transgenic mouse models used in the study of this common neurodegenerative disorder. PMID:20934487

  7. Agile robotic edge finishing system research

    SciTech Connect

    Powell, M.A.

    1995-07-01

    This paper describes a new project undertaken by Sandia National Laboratories to develop an agile, automated, high-precision edge finishing system. The project has a two-year duration and was initiated in October, 1994. This project involves re-designing and adding additional capabilities to an existing finishing workcell at Sandia; and developing intelligent methods for automating process definition and for controlling finishing processes. The resulting system will serve as a prototype for systems that will be deployed into highly flexible automated production lines. The production systems will be used to produce a wide variety of products with limited production quantities and quick turnaround requirements. The prototype system is designed to allow programming, process definition, fixture re-configuration, and process verification to be performed off-line for new products. CAD/CAM (Computer Aided Design/Computer Aided Manufacturing) models of the part will be used to assist with the automated process development and process control tasks. To achieve Sandia`s performance goals, the system will be employ advanced path planning, burr prediction expert systems, automated process definition, statistical process models in a process database, and a two-level control scheme using hybrid position-force control and fuzzy logic control. In this paper, we discuss the progress and the planned system development under this project.

  8. Parallel optimization methods for agile manufacturing

    SciTech Connect

    Meza, J.C.; Moen, C.D.; Plantenga, T.D.; Spence, P.A.; Tong, C.H.; Hendrickson, B.A.; Leland, R.W.; Reese, G.M.

    1997-08-01

    The rapid and optimal design of new goods is essential for meeting national objectives in advanced manufacturing. Currently almost all manufacturing procedures involve the determination of some optimal design parameters. This process is iterative in nature and because it is usually done manually it can be expensive and time consuming. This report describes the results of an LDRD, the goal of which was to develop optimization algorithms and software tools that will enable automated design thereby allowing for agile manufacturing. Although the design processes vary across industries, many of the mathematical characteristics of the problems are the same, including large-scale, noisy, and non-differentiable functions with nonlinear constraints. This report describes the development of a common set of optimization tools using object-oriented programming techniques that can be applied to these types of problems. The authors give examples of several applications that are representative of design problems including an inverse scattering problem, a vibration isolation problem, a system identification problem for the correlation of finite element models with test data and the control of a chemical vapor deposition reactor furnace. Because the function evaluations are computationally expensive, they emphasize algorithms that can be adapted to parallel computers.

  9. "Agile" Battery Technology Transfer-Lessons Learnt

    NASA Astrophysics Data System (ADS)

    Sabatini, P.; Annoni, G.; Grossi, R.; Alia, Sergio; Reulier, David

    2008-09-01

    AGILE, the high energy astrophysics mission of the Italian Space Agency launched on April 23rd 2007, is the first LEO satellite to be powered by Saft's commercially available space qualified MPS176065 rechargeable lithium ion batteries.Saft and Carlo Gavazzi Space (CGS) have achieved a successful technology transfer replacing Ni-H2 batteries with high energy lithium ion batteries in a full speed program (4 months) and with a cost effective approach. The battery system comprises 2 x 24 Saft MPS176065 space qualified Li-ion cells in an 8s3p configuration (3 parallel arrays each composed by 8 series cell) with a nominal capacity of 2 x 480 Wh and an integral autonomous cell balancing system that ensures the maximum possible battery life.The MPS176065 space qualified cell is based on Saft's well proven MP series of prismatic rechargeable Li-ion batteries. It offers an extremely high capacity made possible by the stainless steel prismatic container that makes use of the volume which is otherwise lost when conventional cylindrical cells are packed together. A single prismatic cell has about 20% more volumetric energy density than an equivalent pack of cylindrical cells.

  10. Distributed agile software development for the SKA

    NASA Astrophysics Data System (ADS)

    Wicenec, Andreas; Parsons, Rebecca; Kitaeff, Slava; Vinsen, Kevin; Wu, Chen; Nelson, Paul; Reed, David

    2012-09-01

    The SKA software will most probably be developed by many groups distributed across the globe and coming from dierent backgrounds, like industries and research institutions. The SKA software subsystems will have to cover a very wide range of dierent areas, but still they have to react and work together like a single system to achieve the scientic goals and satisfy the challenging data ow requirements. Designing and developing such a system in a distributed fashion requires proper tools and the setup of an environment to allow for ecient detection and tracking of interface and integration issues in particular in a timely way. Agile development can provide much faster feedback mechanisms and also much tighter collaboration between the customer (scientist) and the developer. Continuous integration and continuous deployment on the other hand can provide much faster feedback of integration issues from the system level to the subsystem developers. This paper describes the results obtained from trialing a potential SKA development environment based on existing science software development processes like ALMA, the expected distribution of the groups potentially involved in the SKA development and experience gained in the development of large scale commercial software projects.

  11. MiRNA-155 and miRNA-132 as potential diagnostic biomarkers for pulmonary tuberculosis: A preliminary study.

    PubMed

    Zheng, Meng-Li; Zhou, Nai-Kang; Luo, Cheng-Hua

    2016-11-01

    In our study, we aimed to profile a panel microRNAs (miRNAs) as potential biomarkers for the early diagnosis of pulmonary tuberculosis (PTB) and to illuminate the molecular mechanisms in the development of PTB. Firstly, gene expression profile of E-GEOD-49951 was downloaded from ArrayExpress database, and quantile-adjusted conditional maximum likelihood method was utilized to identify statistical difference between miRNAs of Mycobacterium tuberculosis (MTB)-infected individuals and healthy subjects. Furthermore, in order to assess the performance of our methodology, random forest (RF) classification model was utilized to identify the top 10 miRNAs with better Area Under The Curve (AUC) using 10-fold cross-validation method. Additionally, Monte Carlo Cross-Validation was repeated 50 times to explore the best miRNAs. In order to learn more about the differentially-expressed miRNAs, the target genes of differentially-expressed miRNAs were retrieved from TargetScan database and Ingenuity Pathways Analysis (IPA) was used to screen out biological pathways where target genes were involved. After normalization, a total of 478 miRNAs with higher than 0.25-fold quantile average across all samples were required. Based on the differential expression analysis, 38 differentially expressed miRNAs were identified when the significance was set as false discovery rate (FDR) < 0.01. Among the top 10 differentially expressed miRNAs, miRNA-155 obtained a highest AUC value 0.976, showing a good performance between PTB and control groups. Similarly, miRNA-449a, miRNA-212 and miRNA-132 revealed also a good performance with AUC values 0.947, 0.931 and 0.930, respectively. Moreover, miRNA-155, miRNA-449a, miRNA-29b-1* and miRNA-132 appeared in 50, 49, 49 and 48 bootstraps. Thus, miRNA-155 and miRNA-132 might be important in the progression of PTB and thereby, might present potential signatures for diagnosis of PTB.

  12. Plasma miRNA Profiles in Pregnant Women Predict Infant Outcomes following Prenatal Alcohol Exposure

    PubMed Central

    Balaraman, Sridevi; Schafer, Jordan J.; Tseng, Alexander M.; Wertelecki, Wladimir; Yevtushok, Lyubov; Zymak-Zakutnya, Natalya; Chambers, Christina D.; Miranda, Rajesh C.

    2016-01-01

    Fetal alcohol spectrum disorders (FASD) are difficult to diagnose since many heavily exposed infants, at risk for intellectual disability, do not exhibit craniofacial dysmorphology or growth deficits. Consequently, there is a need for biomarkers that predict disability. In both animal models and human studies, alcohol exposure during pregnancy resulted in significant alterations in circulating microRNAs (miRNAs) in maternal blood. In the current study, we asked if changes in plasma miRNAs in alcohol-exposed pregnant mothers, either alone or in conjunction with other clinical variables, could predict infant outcomes. Sixty-eight pregnant women at two perinatal care clinics in western Ukraine were recruited into the study. Detailed health and alcohol consumption histories, and 2nd and 3rd trimester blood samples were obtained. Birth cohort infants were assessed by a geneticist and classified as unexposed (UE), heavily prenatally exposed and affected (HEa) or heavily exposed but apparently unaffected (HEua). MiRNAs were assessed in plasma samples using qRT-PCR arrays. ANOVA models identified 11 miRNAs that were all significantly elevated in maternal plasma from the HEa group relative to HEua and UE groups. In a random forest analysis classification model, a combination of high variance miRNAs, smoking history and socioeconomic status classified membership in HEa and UE groups, with a misclassification rate of 13%. The RFA model also classified 17% of the HEua group as UE-like, whereas 83% were HEa-like, at least at one stage of pregnancy. Collectively our data indicate that maternal plasma miRNAs predict infant outcomes, and may be useful to classify difficult-to-diagnose FASD subpopulations. PMID:27828986

  13. Novel and simple electrochemical biosensor monitoring attomolar levels of miRNA-155 in breast cancer.

    PubMed

    Cardoso, Ana R; Moreira, Felismina T C; Fernandes, Rúben; Sales, M Goreti F

    2016-06-15

    This work, describes for the first time, a simple biosensing design to yield an ultrasensitive electrochemical biosensor for a cancer biomarker detection, miRNA-155, with linear response down to the attomolar range. MiRNA-155 was selected for being overexpressed in breast cancer. The biosensor was assembled in two stages: (1) the immobilization of the anti-miRNA-155 that was thiol modified on an Au-screen printed electrode (Au-SPE), followed by (2) blocking the areas of non-specific binding with mercaptosuccinic acid. Atomic force microscopy (AFM) and electrochemical techniques including cyclic voltammetry (CV), impedance spectroscopy (EIS) and square wave voltammetry (SWV) confirmed the surface modification of these devices and their ability to hybridize successfully and stably with miRNA-155. The final biosensor provided a sensitive detection of miRNA-155 from 10 aM to 1.0 nM with a low detection limit (LOD) of 5.7 aM in real human serum samples. Good results were obtained in terms of selectivity towards breast cancer antigen CA-15.3 and bovine serum albumin (BSA). Raw fluid extracts from cell-lines of melanoma did not affect the biosensor response (no significant change of the blank), while raw extracts from breast cancer yielded a positive signal against miRNA-155. This simple and sensitive strategy is a promising alternative for simultaneous quantitative analysis of multiple miRNA in physiological fluids for biomedical research and point-of-care (POC) diagnosis.

  14. Altered expression of miRNAs and methylation of their promoters are correlated in neuroblastoma.

    PubMed

    Maugeri, Marco; Barbagallo, Davide; Barbagallo, Cristina; Banelli, Barbara; Di Mauro, Stefania; Purrello, Francesco; Magro, Gaetano; Ragusa, Marco; Di Pietro, Cinzia; Romani, Massimo; Purrello, Michele

    2016-12-13

    Neuroblastoma is the most common human extracranial solid tumor during infancy. Involvement of several miRNAs in its pathogenesis has been ascertained. Interestingly, most of their encoding genes reside in hypermethylated genomic regions: thus, their tumor suppressor function is normally disallowed in these tumors. To date, the therapeutic role of the demethylating agent 5'-Aza-2 deoxycytidine (5'-AZA) and its effects on miRNAome modulation in neuroblastoma have not been satisfactorily explored. Starting from a high-throughput expression profiling of 754 miRNAs and based on a proper selection, we focused on miR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p as candidate miRNAs for our analysis. They resulted downregulated in four neuroblastoma cell lines with respect to normal adrenal gland. MiRNAs 29a-3p and 34b-3p also resulted downregulated in vivo in a murine neuroblastoma progression model. Unlike the amount of methylation of their encoding gene promoters, all these miRNAs were significantly overexpressed following treatment with 5'-AZA. Transfection with candidate miRNAs mimics significantly decreased neuroblastoma cells proliferation rate. A lower expression of miR-181c was significantly associated to a worse overall survival in a public dataset of 498 neuroblastoma samples (http://r2.amc.nl). Our data strongly suggest that CDK6, DNMT3A, DNMT3B are targets of miR-29a-3p, while CCNE2 and E2F3 are targets of miR-34b-3p. Based on all these data, we propose that miR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p are disallowed tumor suppressor genes in neuroblastoma and suggest them as new therapeutic targets in neuroblastoma.

  15. Possible involvement of miRNAs in tropism of Parvovirus B19.

    PubMed

    Anbarlou, Azadeh; AkhavanRahnama, Mahshid; Atashi, Amir; Soleimani, Masoud; Arefian, Ehsan; Gallinella, Giorgio

    2016-03-01

    Human Parvovirus B19 (PVB19) is one of the most important pathogens that targets erythroid lineage. Many factors were mentioned for restriction to erythroid progenitor cells (EPCs). Previous studies showed that in non-permissive cells VP1 and VP2 (structural proteins) mRNAs were detected but could not translate to proteins. A bioinformatics study showed that this inhibition might be due to specific microRNAs (miRNAs) present in non-permissive cells but not in permissive EPCs. To confirm the hypothesis, we evaluated the effect of miRNAs on VP expression. CD34(+) HSCs were separated from cord blood. Then, CD34(+) cells were treated with differentiation medium to obtain CD36(+) EPCs. To evaluate the effect of miRNAs on VP expression in MCF7 and HEK-293 cell lines (non-permissive cells) and CD36(+) EPCs, dual luciferase assay was performed in presence of shRNAs against Dicer and Drosha to disrupt miRNA biogenesis. QRT-PCR was performed to check down-regulation of Dicer and Drosha after transfection. All measurements were done in triplicate. Data means were compared using one-way ANOVAs. MicroRNA prediction was done by the online microRNA prediction tools. No significant difference was shown in luciferase activity of CD36(+) EPCs after co-transfection with shRNAs, while it was significant in non-permissive cells. Our study revealed that miRNAs may be involved in inhibition of VP expression in non-permissive cells, although further studies are required to demonstrate which miRNAs exactly are involved in regulation of PVB19 replication.

  16. The agile alert system for gamma-ray transients

    SciTech Connect

    Bulgarelli, A.; Trifoglio, M.; Gianotti, F.; Fioretti, V.; Chen, A. W.; Pittori, C.; Verrecchia, F.; Lucarelli, F.; Santolamazza, P.; Fanari, G.; Giommi, P.; Pellizzoni, A.; and others

    2014-01-20

    In recent years, a new generation of space missions has offered great opportunities for discovery in high-energy astrophysics. In this article we focus on the scientific operations of the Gamma-Ray Imaging Detector (GRID) on board the AGILE space mission. AGILE-GRID, sensitive in the energy range of 30 MeV-30 GeV, has detected many γ-ray transients of both galactic and extragalactic origin. This work presents the AGILE innovative approach to fast γ-ray transient detection, which is a challenging task and a crucial part of the AGILE scientific program. The goals are to describe (1) the AGILE Gamma-Ray Alert System, (2) a new algorithm for blind search identification of transients within a short processing time, (3) the AGILE procedure for γ-ray transient alert management, and (4) the likelihood of ratio tests that are necessary to evaluate the post-trial statistical significance of the results. Special algorithms and an optimized sequence of tasks are necessary to reach our goal. Data are automatically analyzed at every orbital downlink by an alert pipeline operating on different timescales. As proper flux thresholds are exceeded, alerts are automatically generated and sent as SMS messages to cellular telephones, via e-mail, and via push notifications from an application for smartphones and tablets. These alerts are crosschecked with the results of two pipelines, and a manual analysis is performed. Being a small scientific-class mission, AGILE is characterized by optimization of both scientific analysis and ground-segment resources. The system is capable of generating alerts within two to three hours of a data downlink, an unprecedented reaction time in γ-ray astrophysics.

  17. The AGILE Alert System for Gamma-Ray Transients

    NASA Astrophysics Data System (ADS)

    Bulgarelli, A.; Trifoglio, M.; Gianotti, F.; Tavani, M.; Parmiggiani, N.; Fioretti, V.; Chen, A. W.; Vercellone, S.; Pittori, C.; Verrecchia, F.; Lucarelli, F.; Santolamazza, P.; Fanari, G.; Giommi, P.; Beneventano, D.; Argan, A.; Trois, A.; Scalise, E.; Longo, F.; Pellizzoni, A.; Pucella, G.; Colafrancesco, S.; Conforti, V.; Tempesta, P.; Cerone, M.; Sabatini, P.; Annoni, G.; Valentini, G.; Salotti, L.

    2014-01-01

    In recent years, a new generation of space missions has offered great opportunities for discovery in high-energy astrophysics. In this article we focus on the scientific operations of the Gamma-Ray Imaging Detector (GRID) on board the AGILE space mission. AGILE-GRID, sensitive in the energy range of 30 MeV-30 GeV, has detected many γ-ray transients of both galactic and extragalactic origin. This work presents the AGILE innovative approach to fast γ-ray transient detection, which is a challenging task and a crucial part of the AGILE scientific program. The goals are to describe (1) the AGILE Gamma-Ray Alert System, (2) a new algorithm for blind search identification of transients within a short processing time, (3) the AGILE procedure for γ-ray transient alert management, and (4) the likelihood of ratio tests that are necessary to evaluate the post-trial statistical significance of the results. Special algorithms and an optimized sequence of tasks are necessary to reach our goal. Data are automatically analyzed at every orbital downlink by an alert pipeline operating on different timescales. As proper flux thresholds are exceeded, alerts are automatically generated and sent as SMS messages to cellular telephones, via e-mail, and via push notifications from an application for smartphones and tablets. These alerts are crosschecked with the results of two pipelines, and a manual analysis is performed. Being a small scientific-class mission, AGILE is characterized by optimization of both scientific analysis and ground-segment resources. The system is capable of generating alerts within two to three hours of a data downlink, an unprecedented reaction time in γ-ray astrophysics.

  18. Semirna: searching for plant miRNAs using target sequences.

    PubMed

    Muñoz-Mérida, Antonio; Perkins, James R; Viguera, Enrique; Thode, Guillermo; Bejarano, Eduardo R; Pérez-Pulido, Antonio J

    2012-04-01

    Many plant genomes are already known, and new ones are being sequenced every year. The next step for researchers is to identify all of the functional elements in these genomes, including the important class of functional elements known as microRNAs (miRNAs), which are involved in posttranscriptional regulatory pathways. However, computational tools for predicting new plant miRNAs are limited, and there is a particular need for tools that can be used easily by laboratory researchers. We present semirna, a new tool for predicting miRNAs in plant genomes, available as a Web server. This tool takes a putative target sequence such as a messenger RNA (mRNA) as input, and allows users to search for miRNAs that target this sequence. It can also be used to determine whether small RNA sequences from massive sequencing analysis represent true miRNAs and to search for miRNAs in new genomes using homology. Semirna has shown a high level of accuracy using various test sets, and gives users the ability to search for miRNAs with several different adjustable parameters. Semirna, a user-friendly and intuitive Web server for predicting miRNA sequences, can be reached at http://www.bioinfocabd.upo.es/semirna/ . It is useful for researchers searching for miRNAs involved in particular pathways, as well as those searching for miRNAs in newly sequenced genomes.

  19. Neuronal Activity Regulates Hippocampal miRNA Expression

    PubMed Central

    Eacker, Stephen M.; Keuss, Matthew J.; Berezikov, Eugene; Dawson, Valina L.; Dawson, Ted M.

    2011-01-01

    Neuronal activity regulates a broad range of processes in the hippocampus, including the precise regulation of translation. Disruptions in proper translational control in the nervous system are associated with a variety of disorders that fall in the autistic spectrum. MicroRNA (miRNA) represent a relatively recently discovered player in the regulation of translation in the nervous system. We have conducted an in depth analysis of how neuronal activity regulates miRNA expression in the hippocampus. Using deep sequencing we exhaustively identify all miRNAs, including 15 novel miRNAs, expressed in hippocampus of the adult mouse. We identified 119 miRNAs documented in miRBase but less than half of these miRNA were expressed at a level greater than 0.1% of total miRNA. Expression profiling following induction of neuronal activity by electroconvulsive shock demonstrates that most miRNA show a biphasic pattern of expression: rapid induction of specific mature miRNA expression followed by a decline in expression. These results have important implications into how miRNAs influence activity-dependent translational control. PMID:21984899

  20. MRNA and miRNA expression patterns associated to pathways linked to metal mixture health effects.

    PubMed

    Martínez-Pacheco, M; Hidalgo-Miranda, A; Romero-Córdoba, S; Valverde, M; Rojas, E

    2014-01-10

    Metals are a threat to human health by increasing disease risk. Experimental data have linked altered miRNA expression with exposure to some metals. MiRNAs comprise a large family of non-coding single-stranded molecules that primarily function to negatively regulate gene expression post-transcriptionally. Although several human populations are exposed to low concentrations of As, Cd and Pb as a mixture, most toxicology research focuses on the individual effects that these metals exert. Thus, this study aims to evaluate global miRNA and mRNA expression changes induced by a metal mixture containing NaAsO2, CdCl2, Pb(C2H3O2)2·3H2O and to predict possible metal-associated disease development under these conditions. Our results show that this metal mixture results in a miRNA expression profile that may be responsible for the mRNA expression changes observed under experimental conditions in which coding proteins are involved in cellular processes, including cell death, growth and proliferation related to the metal-associated inflammatory response and cancer.

  1. Imperfect centered miRNA binding sites are common and can mediate repression of target mRNAs

    PubMed Central

    2014-01-01

    Background MicroRNAs (miRNAs) bind to mRNAs and target them for translational inhibition or transcriptional degradation. It is thought that most miRNA-mRNA interactions involve the seed region at the 5′ end of the miRNA. The importance of seed sites is supported by experimental evidence, although there is growing interest in interactions mediated by the central region of the miRNA, termed centered sites. To investigate the prevalence of these interactions, we apply a biotin pull-down method to determine the direct targets of ten human miRNAs, including four isomiRs that share centered sites, but not seeds, with their canonical partner miRNAs. Results We confirm that miRNAs and their isomiRs can interact with hundreds of mRNAs, and that imperfect centered sites are common mediators of miRNA-mRNA interactions. We experimentally demonstrate that these sites can repress mRNA activity, typically through translational repression, and are enriched in regions of the transcriptome bound by AGO. Finally, we show that the identification of imperfect centered sites is unlikely to be an artifact of our protocol caused by the biotinylation of the miRNA. However, the fact that there was a slight bias against seed sites in our protocol may have inflated the apparent prevalence of centered site-mediated interactions. Conclusions Our results suggest that centered site-mediated interactions are much more frequent than previously thought. This may explain the evolutionary conservation of the central region of miRNAs, and has significant implications for decoding miRNA-regulated genetic networks, and for predicting the functional effect of variants that do not alter protein sequence. PMID:24629056

  2. Creativity in Agile Systems Development: A Literature Review

    NASA Astrophysics Data System (ADS)

    Conboy, Kieran; Wang, Xiaofeng; Fitzgerald, Brian

    Proponents of agile methods claim that enabling, fostering and driving creativity is the key motivation that differentiates agile methods from their more traditional, beauraucratic counterparts. However, there is very little rigorous research to support this claim. Like most of their predecessors, the development and promotion of these methods has been almost entirely driven by practitioners and consultants, with little objective validation from the research community. This lack of validation is particularly relevant for SMEs, given that many of their project teams typify the environment to which agile methods are most suited i.e. small, co-located teams with diverse, blended skills in unstructured, sometimes even chaotic surroundings. This paper uses creativity theory as a lens to review the current agile method literature to understand exactly how much we know about the extent to which creativity actually occurs in these agile environments. The study reveals many gaps and conflict of opinion in the body of knowledge in its current state and identifies many avenues for further research.

  3. The Southern Argentine Agile Meteor Radar (SAAMER)

    NASA Astrophysics Data System (ADS)

    Janches, Diego

    2014-11-01

    The Southern Argentina Agile Meteor Radar (SAAMER) is a new generation system deployed in Rio Grande, Tierra del Fuego, Argentina (53 S) in May 2008. SAAMER transmits 10 times more power than regular meteor radars, and uses a newly developed transmitting array, which focuses power upward instead of the traditional single-antenna-all-sky configuration. The system is configured such that the transmitter array can also be utilized as a receiver. The new design greatly increases the sensitivity of the radar enabling the detection of large number of particles at low zenith angles. The more concentrated transmitted power enables additional meteor studies besides those typical of these systems based on the detection of specular reflections, such as routine detections of head echoes and non-specular trails, previously only possible with High Power and Large Aperture radars. In August 2010, SAAMER was upgraded to a system capable to determine meteoroid orbital parameters. This was achieved by adding two remote receiving stations approximately 10 km away from the main site in near perpendicular directions. The upgrade significantly expands the science that is achieved with this new radar enabling us to study the orbital properties of the interplanetary dust environment. Because of the unique geographical location, SAAMER allows for additional inter-hemispheric comparison with measurements from Canadian Meteor Orbit Radar, which is geographically conjugate. Initial surveys show, for example, that SAAMER observes a very strong contribution of the South Toroidal Sporadic meteor source, of which limited observational data is available. In addition, SAAMER offers similar unique capabilities for meteor showers and streams studies given the range of ecliptic latitudes that the system enables detailed study of showers at high southern latitudes (e.g July Phoenicids or Puppids complex). Finally, SAAMER is ideal for the deployment of complementary instrumentation in both, permanent

  4. Genome-wide miRNA seeds prediction in Archaea.

    PubMed

    Wang, Shengqin; Xu, Yuming; Lu, Zuhong

    2014-01-01

    Growing evidence indicates that miRNA genes exist in the archaeal genome, though the functional role of such noncoding RNA remains unclear. Here, we integrated the phylogenetic information of available archaeal genomes to predict miRNA seeds (typically defined as the 2-8 nucleotides of mature miRNAs) on the genomic scale. Finally, we found 2649 candidate seeds with significant conservation signal. Eleven of 29 unique seeds from previous study support our result (P value <0.01), which demonstrates that the pipeline is suitable to predict experimentally detectable miRNA seeds. The statistical significance of the overlap between the detected archaeal seeds and known eukaryotic seeds shows that the miRNA may evolve before the divergence of these two domains of cellular life. In addition, miRNA targets are enriched for genes involved in transcriptional regulation, which is consistent with the situation in eukaryote. Our research will enhance the regulatory network analysis in Archaea.

  5. miRNA Inhibition in Tissue Engineering and Regenerative Medicine

    PubMed Central

    Beavers, Kelsey R.; Nelson, Christopher E.; Duvall, Craig L.

    2014-01-01

    MicroRNA (miRNA) are noncoding RNA that provide an endogenous negative feedback mechanism for translation of messenger RNA (mRNA) into protein. Single miRNAs can regulate hundreds of mRNAs, enabling miRNAs to orchestrate robust biological responses by simultaneously impacting multiple gene networks. MiRNAs can act as master regulators of normal and pathological tissue development, homeostasis, and repair, which has recently motivated expanding efforts toward development of technologies for therapeutically modulating miRNA activity for regenerative medicine and tissue engineering applications. This review highlights the tools currently available for miRNA inhibition and their recent therapeutic applications for improving tissue repair. PMID:25553957

  6. MiRNA inhibition in tissue engineering and regenerative medicine.

    PubMed

    Beavers, Kelsey R; Nelson, Christopher E; Duvall, Craig L

    2015-07-01

    MicroRNAs (miRNAs) are noncoding RNAs that provide an endogenous negative feedback mechanism for translation of messenger RNA (mRNA) into protein. Single miRNAs can regulate hundreds of mRNAs, enabling miRNAs to orchestrate robust biological responses by simultaneously impacting multiple gene networks. MiRNAs can act as master regulators of normal and pathological tissue development, homeostasis, and repair, which has motivated expanding efforts toward the development of technologies for therapeutically modulating miRNA activity for regenerative medicine and tissue engineering applications. This review highlights the tools currently available for miRNA inhibition and their recent therapeutic applications for improving tissue repair.

  7. Epigenetic regulation of miRNAs in cancer.

    PubMed

    Fabbri, Muller; Calore, Federica; Paone, Alessio; Galli, Roberta; Calin, George A

    2013-01-01

    MicroRNAs (miRNAs) are short noncoding RNAs with gene regulatory functions. It has been demonstrated that the genes encoding for miRNAs undergo the same regulatory epigenetic processes of protein coding genes. In turn, a specific subgroup of miRNAs, called epi-miRNAs, is able to directly target key enzymatic effectors of the epigenetic machinery (such as DNA methyltransferases, histone deacetylases, and polycomb genes), therefore indirectly affecting the expression of epigenetically regulated oncogenes and tumor suppressor genes. Also, several of the epigenetic drugs currently approved as anticancer agents affect the expression of miRNAs and this might explain part of their mechanism of action. This chapter focuses on the tight relationship between epigenetics and miRNAs and provides some insights on the translational implications of these findings, leading to the upcoming introduction of epigenetically related miRNAs in the treatment of cancer.

  8. Analysis and optimization of preliminary aircraft configurations in relationship to emerging agility metrics

    NASA Technical Reports Server (NTRS)

    Sandlin, Doral R.; Bauer, Brent Alan

    1993-01-01

    This paper discusses the development of a FORTRAN computer code to perform agility analysis on aircraft configurations. This code is to be part of the NASA-Ames ACSYNT (AirCraft SYNThesis) design code. This paper begins with a discussion of contemporary agility research in the aircraft industry and a survey of a few agility metrics. The methodology, techniques and models developed for the code are then presented. Finally, example trade studies using the agility module along with ACSYNT are illustrated. These trade studies were conducted using a Northrop F-20 Tigershark aircraft model. The studies show that the agility module is effective in analyzing the influence of common parameters such as thrust-to-weight ratio and wing loading on agility criteria. The module can compare the agility potential between different configurations. In addition one study illustrates the module's ability to optimize a configuration's agility performance.

  9. Development of a Computer Program for Analyzing Preliminary Aircraft Configurations in Relationship to Emerging Agility Metrics

    NASA Technical Reports Server (NTRS)

    Bauer, Brent

    1993-01-01

    This paper discusses the development of a FORTRAN computer code to perform agility analysis on aircraft configurations. This code is to be part of the NASA-Ames ACSYNT (AirCraft SYNThesis) design code. This paper begins with a discussion of contemporary agility research in the aircraft industry and a survey of a few agility metrics. The methodology, techniques and models developed for the code are then presented. Finally, example trade studies using the agility module along with ACSYNT are illustrated. These trade studies were conducted using a Northrop F-20 Tigershark aircraft model. The studies show that the agility module is effective in analyzing the influence of common parameters such as thrust-to-weight ratio and wing loading on agility criteria. The module can compare the agility potential between different configurations. In addition, one study illustrates the module's ability to optimize a configuration's agility performance.

  10. The measurement and improvement of the lateral agility of the F-18

    NASA Technical Reports Server (NTRS)

    Eggold, David P.; Valasek, John; Downing, David R.

    1991-01-01

    The effect of vehicle configuration and flight control system performance on the roll agility of a modern fighter aircraft has been investigated. A batch simulation of a generic F-18 Hornet was used to study the roll agility as measured by the time to roll through 90 deg metric. Problems discussed include definition of agility, factors affecting the agility of a vehicle, the development of the time to roll through 90 deg agility metric, and a simulation experiment. It is concluded that the integral of stability or wind axis roll rate should be used as a measure of the roll measure traversed. The time through roll angle 90 deg metric is considered to be a good metric for measuring the transient performance aspect of agility. Roll agility of the F-18, as measured by 90 deg metric, can be improved by 10 to 30 percent. Compatible roll and rudder actuator rates can significantly affect 90 deg agility metric.

  11. Exosomes as miRNA Carriers: Formation–Function–Future

    PubMed Central

    Yu, Xiaojie; Odenthal, Margarete; Fries, Jochen W. U.

    2016-01-01

    Exosomes, which are one of the smallest extracellular vesicles released from cells, have been shown to carry different nucleic acids, including microRNAs (miRNAs). miRNAs significantly regulate cell growth and metabolism by posttranscriptional inhibition of gene expression. The rapidly changing understanding of exosomes’ formation and function in delivering miRNAs from cell to cell has prompted us to review current knowledge in exosomal miRNA secretion mechanisms as well as possible therapeutic applications for personalized medicine. PMID:27918449

  12. Exploration of miRNA families for hypotheses generation

    NASA Astrophysics Data System (ADS)

    Kamanu, Timothy K. K.; Radovanovic, Aleksandar; Archer, John A. C.; Bajic, Vladimir B.

    2013-10-01

    Technological improvements have resulted in increased discovery of new microRNAs (miRNAs) and refinement and enrichment of existing miRNA families. miRNA families are important because they suggest a common sequence or structure configuration in sets of genes that hint to a shared function. Exploratory tools to enhance investigation of characteristics of miRNA families and the functions of family-specific miRNA genes are lacking. We have developed, miRNAVISA, a user-friendly web-based tool that allows customized interrogation and comparisons of miRNA families for hypotheses generation, and comparison of per-species chromosomal distribution of miRNA genes in different families. This study illustrates hypothesis generation using miRNAVISA in seven species. Our results unveil a subclass of miRNAs that may be regulated by genomic imprinting, and also suggest that some miRNA families may be species-specific, as well as chromosome- and/or strand-specific.

  13. miRNA expression during prickly pear cactus fruit development.

    PubMed

    Rosas-Cárdenas, Flor de Fátima; Caballero-Pérez, Juan; Gutiérrez-Ramos, Ximena; Marsch-Martínez, Nayelli; Cruz-Hernández, Andrés; de Folter, Stefan

    2015-02-01

    miRNAs are a class of small non-coding RNAs that regulate gene expression. They are involved in the control of many developmental processes, including fruit development. The increasing amount of information on miRNAs, on their expression, abundance, and conservation between various species, provides a new opportunity to study the role of miRNAs in non-model plant species. In this work, we used a combination of Northern blot and tissue print hybridization analysis to identify conserved miRNAs expressed during prickly pear cactus (Opuntia ficus indica) fruit development. Comparative profiling detected the expression of 34 miRNAs, which were clustered in three different groups that were associated with the different phases of fruit development. Variation in the level of miRNA expression was observed. Gradual expression increase of several miRNAs was observed during fruit development, including miR164. miR164 was selected for stem-loop RT-PCR and for a detailed spatial-temporal expression analysis. At early floral stages, miR164 was mainly localized in meristematic tissues, boundaries and fusion zones, while it was more homogenously expressed in fruit tissues. Our results provide the first evidence of miRNA expression in the prickly pear cactus and provide the basis for future research on miRNAs in Opuntia. Moreover, our analyses suggest that miR164 plays different roles during prickly pear cactus fruit development.

  14. miRNAs: roles and clinical applications in vascular disease.

    PubMed

    Jamaluddin, Md Saha; Weakley, Sarah M; Zhang, Lidong; Kougias, Panagiotis; Lin, Peter H; Yao, Qizhi; Chen, Changyi

    2011-01-01

    miRNAs are small, endogenously expressed noncoding RNAs that regulate gene expression, mainly at the post-transcriptional level, via degradation or translational inhibition of their target mRNAs. Functionally, an individual miRNA can regulate the expression of multiple target genes. The study of miRNAs is rapidly growing and recent studies have revealed a significant role of miRNAs in vascular biology and disease. Many miRNAs are highly expressed in the vasculature, and their expression is dysregulated in diseased vessels. Several miRNAs have been found to be critical modulators of vascular pathologies, such as atherosclerosis, lipoprotein metabolism, inflammation, arterial remodeling, angiogenesis, smooth muscle cell regeneration, hypertension, apoptosis, neointimal hyperplasia and signal transduction pathways. Thus, miRNAs may serve as novel biomarkers and/or therapeutic targets for vascular disease. This article summarizes the current studies related to the disease correlations and functional roles of miRNAs in the vascular system and discusses the potential applications of miRNAs in vascular disease.

  15. Comparative analysis of known miRNAs across platyhelminths.

    PubMed

    Jin, Xiaoliang; Lu, Lixia; Su, Hailong; Lou, Zhongzi; Wang, Fang; Zheng, Yadong; Xu, Guo-Tong

    2013-08-01

    MicroRNAs (miRNAs) are a subtype of small regulatory RNAs that are involved in numerous biological processes through small RNA-induced silencing networks. In an attempt to explore the phylogeny of miRNAs across five platyhelminths, we integrated annotated miRNAs and their full genomes. We identified conserved miRNA clusters and, in particular, miR-71/2 was conserved from planarian to parasitic flatworms and was expanded in free-living Schmidtea mediterranea. Analysis of 22 miRNA loci provided compelling evidence that most known miRNAs are conserved across platyhelminths. Meanwhile, we also observed alterations of known protein-coding genes flanking miRNA(s), such as transcriptional direction conversion and locus relocation, in around ~ 41% of 22 known miRNA loci. Compared with Echinococcus multilocularis, the majority of these events occurred in evolution-distant Hymenolepis microstoma, Schistosoma japonicum or/and S. mediterranea. These results imply rearrangement events occurred near the known miRNA loci.

  16. miRNAs as biomarkers of atrial fibrillation.

    PubMed

    Gomes da Silva, Ananília Medeiros; Silbiger, Vivian Nogueira

    2014-12-01

    Atrial fibrillation (AF) is a highly prevalent arrhythmia with pronounced morbidity and mortality. Genetics analysis has established electrophysiological substrates, which determine individual vulnerability to AF occurrence and maintenance. MicroRNAs (miRNAs) found in virtually all organisms function as negative regulators of protein-coding genes. Several studies have suggested a role for miRNAs in the regulation of cardiac excitability and arrhythmogenesis. This review is based on 18 studies conducted between 2009 and 2013 to investigate the association of miRNAs with AF. miRNAs are discussed here as candidate biomarkers for AF in blood and cardiac tissues and as potential targets for AF therapy.

  17. Methylation of miRNA genes and oncogenesis.

    PubMed

    Loginov, V I; Rykov, S V; Fridman, M V; Braga, E A

    2015-02-01

    Interaction between microRNA (miRNA) and messenger RNA of target genes at the posttranscriptional level provides fine-tuned dynamic regulation of cell signaling pathways. Each miRNA can be involved in regulating hundreds of protein-coding genes, and, conversely, a number of different miRNAs usually target a structural gene. Epigenetic gene inactivation associated with methylation of promoter CpG-islands is common to both protein-coding genes and miRNA genes. Here, data on functions of miRNAs in development of tumor-cell phenotype are reviewed. Genomic organization of promoter CpG-islands of the miRNA genes located in inter- and intragenic areas is discussed. The literature and our own results on frequency of CpG-island methylation in miRNA genes from tumors are summarized, and data regarding a link between such modification and changed activity of miRNA genes and, consequently, protein-coding target genes are presented. Moreover, the impact of miRNA gene methylation on key oncogenetic processes as well as affected signaling pathways is discussed.

  18. Pathways to agility in the production of neutron generators

    SciTech Connect

    Stoltz, R.E.; Beavis, L.C.; Cutchen, J.T.; Garcia, P.; Gurule, G.A.; Harris, R.N.; McKey, P.C.; Williams, D.W.

    1994-02-01

    This report is the result of a study team commissioned to explore pathways for increased agility in the manufacture of neutron generators. As a part of Sandia`s new responsibility for generator production, the goal of the study was to identify opportunities to reduce costs and increase flexibility in the manufacturing operation. Four parallel approaches (or pathways) were recommended: (1) Know the goal, (2) Use design leverage effectively, (3) Value simplicity, and (4) Configure for flexibility. Agility in neutron generator production can be enhanced if all of these pathways are followed. The key role of the workforce in achieving agility was also noted, with emphasis on ownership, continuous learning, and a supportive environment.

  19. Onshore and Offshore Outsourcing with Agility: Lessons Learned

    NASA Astrophysics Data System (ADS)

    Kussmaul, Clifton

    This chapter reflects on case study based an agile distributed project that ran for approximately three years (from spring 2003 to spring 2006). The project involved (a) a customer organization with key personnel distributed across the US, developing an application with rapidly changing requirements; (b) onshore consultants with expertise in project management, development processes, offshoring, and relevant technologies; and (c) an external offsite development team in a CMM-5 organization in southern India. This chapter is based on surveys and discussions with multiple participants. The several years since the project was completed allow greater perspective on both the strengths and weaknesses, since the participants can reflect on the entire life of the project, and compare it to subsequent experiences. Our findings emphasize the potential for agile project management in distributed software development, and the importance of people and interactions, taking many small steps to find and correct errors, and matching the structures of the project and product to support implementation of agility.

  20. Decision Support for Iteration Scheduling in Agile Environments

    NASA Astrophysics Data System (ADS)

    Szőke, Ákos

    Today’s software business development projects often lay claim to low-risk value to the customers in order to be financed. Emerging agile processes offer shorter investment periods, faster time-to-market and better customer satisfaction. To date, however, in agile environments there is no sound methodological schedule support contrary to the traditional plan-based approaches. To address this situation, we present an agile iteration scheduling method whose usefulness is evaluated with post-mortem simulation. It demonstrates that the method can significantly improve load balancing of resources (cca. 5×), produce higher quality and lower-risk feasible schedule, and provide more informed and established decisions by optimized schedule production. Finally, the paper analyzes benefits and issues from the use of this method.

  1. The AGILE Mission and Gamma-Ray Bursts

    SciTech Connect

    Longo, Francesco; Tavani, M.; Barbiellini, G.; Argan, A.; Basset, M.; Boffelli, F.; Bulgarelli, A.; Caraveo, P.; Cattaneo, P.; Chen, A.; Costa, E.; Del Monte, E.; Di Cocco, G.; Di Persio, G.; Donnarumma, I.; Feroci, M.; Fiorini, M.; Foggetta, L.; Froysland, T.; Frutti, M.

    2007-05-01

    The AGILE Mission will explore the gamma-ray Universe with a very innovative instrument combining for the first time a gamma-ray imager and a hard X-ray imager. AGILE will be operational at the beginning of 2007 and it will provide crucial data for the study of Active Galactic Nuclei, Gamma-Ray Bursts, unidentified gamma-ray sources, Galactic compact objects, supernova remnants, TeV sources, and fundamental physics by microsecond timing. The AGILE instrument is designed to simultaneously detect and image photons in the 30 MeV - 50 GeV and 15 - 45 keV energy bands with excellent imaging and timing capabilities, and a large field of view covering {approx} 1/5 of the entire sky at energies above 30 MeV. A CsI calorimeter is capable of GRB triggering in the energy band 0.3-50 MeV. The broadband detection of GRBs and the study of implications for particle acceleration and high energy emission are primary goals of the mission. AGILE can image GRBs with 2-3 arcminute error boxes in the hard X-ray range, and provide broadband photon-by photon detection in the 15-45 keV, 03-50 MeV, and 30 MeV-30 GeV energy ranges. Microsecond on-board photon tagging and a {approx} 100 microsecond gamma-ray detection deadtime will be crucial for fast GRB timing. On-board calculated GRB coordinates and energy fluxes will be quickly transmitted to the ground by an ORBCOMM transceiver. AGILE is now (January 2007) undergoing final satellite integration and testing. The PLS V launch is planned in spring 2007. AGILE is then foreseen to be fully operational during the summer of 2007.

  2. The Perfect Process Storm: Integration of CMMI, Agile, and Lean Six Sigma

    DTIC Science & Technology

    2012-12-01

    projects using similar iterative methodologies includ- ing Scrum , Crystal, and Feature-driven Development leading to the meeting of the Agile...1986 Lean Six Sigma (LSS) Late 1990’s Lean Production 1990 CMM 1987 - 2002 CMMI 2002V1.3 2010 Agile XP 1996 Agile Manifesto 2001 Scrum 2001...Business Process Improvement. Most recently his efforts have targeted BPI for 22 Agile SCRUM projects, deploy- ing Project and Process Management

  3. Rapid divergence and high diversity of miRNAs and miRNA targets in the Camelineae.

    PubMed

    Smith, Lisa M; Burbano, Hernán A; Wang, Xi; Fitz, Joffrey; Wang, George; Ural-Blimke, Yonca; Weigel, Detlef

    2015-02-01

    MicroRNAs (miRNAs) are short RNAs involved in gene regulation through translational inhibition and transcript cleavage. After processing from imperfect fold-back structures, miRNAs are incorporated into RNA-induced silencing complexes (RISCs) before targeting transcripts with varying degrees of complementarity. Some miRNAs are evolutionarily deep-rooted, and sequence complementarity with their targets is maintained through purifying selection. Both Arabidopsis and Capsella belong to the tribe Camelineae in the Brassicaceae, with Capsella rubella serving as an outgroup to the genus Arabidopsis. The genome sequence of C. rubella has recently been released, which allows characterization of its miRNA complement in comparison with Arabidopsis thaliana and Arabidopsis lyrata. Through next-generation sequencing, we identify high-confidence miRNA candidates specific to the C. rubella lineage. Only a few lineage-specific miRNAs have been studied for evolutionary constraints, and there have been no systematic studies of miRNA target diversity within or divergence between closely related plant species. Therefore we contrast sequence variation in miRNAs and their targets within A. thaliana, and between A. thaliana, A. lyrata and C. rubella. We document a surprising amount of small-scale variation in miRNA-target pairs, where many miRNAs are predicted to have species-specific targets in addition to ones that are shared between species. Our results emphasize that the transitive nature of many miRNA-target pairs can be observed even on a relatively short evolutionary time-scale, with non-random occurrences of differences in miRNAs and their complements in the miRNA precursors, the miRNA* sequences.

  4. Lean and Agile Development of the AITS Ground Software System

    NASA Astrophysics Data System (ADS)

    Richters, Mark; Dutruel, Etienne; Mecredy, Nicolas

    2013-08-01

    We present the ongoing development of a new ground software system used for integrating, testing and operating spacecraft. The Advanced Integration and Test Services (AITS) project aims at providing a solution for electrical ground support equipment and mission control systems in future Astrium Space Transportation missions. Traditionally ESA ground or flight software development projects are conducted according to a waterfall-like process as specified in the ECSS-E-40 standard promoted by ESA in the European industry. In AITS a decision was taken to adopt an agile development process. This work could serve as a reference for future ESA software projects willing to apply agile concepts.

  5. Blood born miRNAs signatures that can serve as disease specific biomarkers are not significantly affected by overall fitness and exercise.

    PubMed

    Backes, Christina; Leidinger, Petra; Keller, Andreas; Hart, Martin; Meyer, Tim; Meese, Eckart; Hecksteden, Anne

    2014-01-01

    Blood born micro(mi)RNA expression pattern have been reported for various human diseases with signatures specific for diseases. To evaluate these biomarkers, it is mandatory to know possible changes of miRNA signatures in healthy individuals under different physiological conditions. We analyzed the miRNA expression in peripheral blood of elite endurance athletes and moderatly active controls. Blood drawing was done before and after exhaustive exercise in each group. After Benjamini-Hochberg adjustment we did not find any miRNA with significant p-values when comparing miRNA expression between the different groups. We found, however, 24 different miRNAs with an expression fold change of minimum 1.5 in at least one of the comparisons (athletes before vs after exercise, athletes before exercise vs controls and athletes after exercise vs controls). The observed changes are not significant in contrast to the expression changes of the blood born miRNA expression reported for many human diseases. These data support the idea of disease associated miRNA patterns useful as biomarkers that are not readily altered by physiological conditions.

  6. Ewing’s Sarcoma: An Analysis of miRNA Expression Profiles and Target Genes in Paraffin-Embedded Primary Tumor Tissue

    PubMed Central

    Parafioriti, Antonina; Bason, Caterina; Armiraglio, Elisabetta; Calciano, Lucia; Daolio, Primo Andrea; Berardocco, Martina; Di Bernardo, Andrea; Colosimo, Alessia; Luksch, Roberto; Berardi, Anna C.

    2016-01-01

    The molecular mechanism responsible for Ewing’s Sarcoma (ES) remains largely unknown. MicroRNAs (miRNAs), a class of small non-coding RNAs able to regulate gene expression, are deregulated in tumors and may serve as a tool for diagnosis and prediction. However, the status of miRNAs in ES has not yet been thoroughly investigated. This study compared global miRNAs expression in paraffin-embedded tumor tissue samples from 20 ES patients, affected by primary untreated tumors, with miRNAs expressed in normal human mesenchymal stromal cells (MSCs) by microarray analysis. A miRTarBase database was used to identify the predicted target genes for differentially expressed miRNAs. The miRNAs microarray analysis revealed distinct patterns of miRNAs expression between ES samples and normal MSCs. 58 of the 954 analyzed miRNAs were significantly differentially expressed in ES samples compared to MSCs. Moreover, the qRT-PCR analysis carried out on three selected miRNAs showed that miR-181b, miR-1915 and miR-1275 were significantly aberrantly regulated, confirming the microarray results. Bio-database analysis identified BCL-2 as a bona fide target gene of the miR-21, miR-181a, miR-181b, miR-29a, miR-29b, miR-497, miR-195, miR-let-7a, miR-34a and miR-1915. Using paraffin-embedded tissues from ES patients, this study has identified several potential target miRNAs and one gene that might be considered a novel critical biomarker for ES pathogenesis. PMID:27144561

  7. Massive analysis of cDNA Ends (MACE) and miRNA expression profiling identifies proatherogenic pathways in chronic kidney disease.

    PubMed

    Zawada, Adam M; Rogacev, Kyrill S; Müller, Sören; Rotter, Björn; Winter, Peter; Fliser, Danilo; Heine, Gunnar H

    2014-01-01

    Epigenetic dysregulation contributes to the high cardiovascular disease burden in chronic kidney disease (CKD) patients. Although microRNAs (miRNAs) are central epigenetic regulators, which substantially affect the development and progression of cardiovascular disease (CVD), no data on miRNA dysregulation in CKD-associated CVD are available until now. We now performed high-throughput miRNA sequencing of peripheral blood mononuclear cells from ten clinically stable hemodialysis (HD) patients and ten healthy controls, which allowed us to identify 182 differentially expressed miRNAs (e.g., miR-21, miR-26b, miR-146b, miR-155). To test biological relevance, we aimed to connect miRNA dysregulation to differential gene expression. Genome-wide gene expression profiling by MACE (Massive Analysis of cDNA Ends) identified 80 genes to be differentially expressed between HD patients and controls, which could be linked to cardiovascular disease (e.g., KLF6, DUSP6, KLF4), to infection / immune disease (e.g., ZFP36, SOCS3, JUND), and to distinct proatherogenic pathways such as the Toll-like receptor signaling pathway (e.g., IL1B, MYD88, TICAM2), the MAPK signaling pathway (e.g., DUSP1, FOS, HSPA1A), and the chemokine signaling pathway (e.g., RHOA, PAK1, CXCL5). Formal interaction network analysis proved biological relevance of miRNA dysregulation, as 68 differentially expressed miRNAs could be connected to 47 reciprocally expressed target genes. Our study is the first comprehensive miRNA analysis in CKD that links dysregulated miRNA expression with differential expression of genes connected to inflammation and CVD. After recent animal data suggested that targeting miRNAs is beneficial in experimental CVD, our data may now spur further research in the field of CKD-associated human CVD.

  8. Massive analysis of cDNA Ends (MACE) and miRNA expression profiling identifies proatherogenic pathways in chronic kidney disease

    PubMed Central

    Zawada, Adam M; Rogacev, Kyrill S; Müller, Sören; Rotter, Björn; Winter, Peter; Fliser, Danilo; Heine, Gunnar H

    2014-01-01

    Epigenetic dysregulation contributes to the high cardiovascular disease burden in chronic kidney disease (CKD) patients. Although microRNAs (miRNAs) are central epigenetic regulators, which substantially affect the development and progression of cardiovascular disease (CVD), no data on miRNA dysregulation in CKD-associated CVD are available until now. We now performed high-throughput miRNA sequencing of peripheral blood mononuclear cells from ten clinically stable hemodialysis (HD) patients and ten healthy controls, which allowed us to identify 182 differentially expressed miRNAs (e.g., miR-21, miR-26b, miR-146b, miR-155). To test biological relevance, we aimed to connect miRNA dysregulation to differential gene expression. Genome-wide gene expression profiling by MACE (Massive Analysis of cDNA Ends) identified 80 genes to be differentially expressed between HD patients and controls, which could be linked to cardiovascular disease (e.g., KLF6, DUSP6, KLF4), to infection / immune disease (e.g., ZFP36, SOCS3, JUND), and to distinct proatherogenic pathways such as the Toll-like receptor signaling pathway (e.g., IL1B, MYD88, TICAM2), the MAPK signaling pathway (e.g., DUSP1, FOS, HSPA1A), and the chemokine signaling pathway (e.g., RHOA, PAK1, CXCL5). Formal interaction network analysis proved biological relevance of miRNA dysregulation, as 68 differentially expressed miRNAs could be connected to 47 reciprocally expressed target genes. Our study is the first comprehensive miRNA analysis in CKD that links dysregulated miRNA expression with differential expression of genes connected to inflammation and CVD. After recent animal data suggested that targeting miRNAs is beneficial in experimental CVD, our data may now spur further research in the field of CKD-associated human CVD. PMID:24184689

  9. A Comprehensive Prescription for Plant miRNA Identification

    PubMed Central

    Alptekin, Burcu; Akpinar, Bala A.; Budak, Hikmet

    2017-01-01

    microRNAs (miRNAs) are tiny ribo-regulatory molecules involved in various essential pathways for persistence of cellular life, such as development, environmental adaptation, and stress response. In recent years, miRNAs have become a major focus in molecular biology because of their functional and diagnostic importance. This interest in miRNA research has resulted in the development of many specific software and pipelines for the identification of miRNAs and their specific targets, which is the key for the elucidation of miRNA-modulated gene expression. While the well-recognized importance of miRNAs in clinical research pushed the emergence of many useful computational identification approaches in animals, available software and pipelines are fewer for plants. Additionally, existing approaches suffers from mis-identification and annotation of plant miRNAs since the miRNA mining process for plants is highly prone to false-positives, particularly in cereals which have a highly repetitive genome. Our group developed a homology-based in silico miRNA identification approach for plants, which utilizes two Perl scripts “SUmirFind” and “SUmirFold” and since then, this method helped identify many miRNAs particularly from crop species such as Triticum or Aegliops. Herein, we describe a comprehensive updated guideline by the implementation of two new scripts, “SUmirPredictor” and “SUmirLocator,” and refinements to our previous method in order to identify genuine miRNAs with increased sensitivity in consideration of miRNA identification problems in plants. Recent updates enable our method to provide more reliable and precise results in an automated fashion in addition to solutions for elimination of most false-positive predictions, miRNA naming and miRNA mis-annotation. It also provides a comprehensive view to genome/transcriptome-wide location of miRNA precursors as well as their association with transposable elements. The “SUmirPredictor” and

  10. Expression profiles of miRNAs in Gossypium raimondii *

    PubMed Central

    Ma, Jun; Guo, Teng-long; Wang, Qing-lian; Wang, Kun-bo; Sun, Run-run; Zhang, Bao-hong

    2015-01-01

    miRNAs are a class of conserved, small, endogenous, and non-protein-coding RNA molecules with 20–24 nucleotides (nt) in length that function as post-transcriptional modulators of gene expression in eukaryotic cells. Functional studies have demonstrated that plant miRNAs are involved in the regulation of a wide range of plant developmental processes. To date, however, no research has been carried out to study the expression profiles of miRNAs in Gossypium raimondii, a model cotton species. We selected 16 miRNAs to profile their tissue-specific expression patterns in G. raimondii four different tissues, and these miRNAs are reported to play important roles in plant growth and development. Our results showed that the expression levels of these miRNAs varied significantly from one to another in a tissue-dependent manner. Eight miRNAs, including miR-159, miR-162, miR-164, miR-172, miR-390, miR-395, miR-397, and miR-398, exhibited exclusively high expression levels in flower buds, suggesting that these miRNAs may play significant roles in floral development. The expression level of miR-164 was relatively high in shoots beside flower buds, implying that the function of miR-164 is not only limited to floral development but it may also play an important role in shoot development. Certain miRNAs such as miR-166 and miR-160 were extremely highly expressed in all of the four tissues tested compared with other miRNAs investigated, suggesting that they may play regulatory roles at multiple development stages. This study will contribute to future studies on the functional characterization of miRNAs in cotton. PMID:25845363

  11. Roles of host and viral microRNAs in human cytomegalovirus biology

    PubMed Central

    Dhuruvasan, Kavitha; Sivasubramanian, Geetha; Pellett, Philip E.

    2011-01-01

    Human cytomegalovirus (HCMV) has a relatively large and complex genome, a protracted lytic replication cycle, and employs a strategy of replicational latency as part of its lifelong persistence in the infected host. An important form of gene regulation in plants and animals revolves around a type of small RNA known as microRNA (miRNA). miRNAs can serve as major regulators of key developmental pathways, as well as provide subtle forms of regulatory control. The human genome encodes over 900 miRNAs, and miRNAs are also encoded by some viruses, including HCMV, which encodes at least 14 miRNAs. Some of the HCMV miRNAs are known to target both viral and cellular genes, including important immunomodulators. In addition to expressing their own miRNAs, infections with some viruses, including HCMV, can result in changes in the expression of cellular miRNAs that benefit virus replication. In this review, we summarize the connections between miRNAs and HCMV biology. We describe the nature of miRNA genes, miRNA biogenesis and modes of action, methods for studying miRNAs, HCMV-encoded miRNAs, effects of HCMV infection on cellular miRNA expression, roles of miRNAs in HCMV biology, and possible HCMV-related diagnostic and therapeutic applications of miRNAs. PMID:20969901

  12. Establishment of a canine mammary gland tumor cell line and characterization of its miRNA expression

    PubMed Central

    Sunden, Yuji; Sugiyama, Akihiko; Azuma, Kazuo; Murahata, Yusuke; Tsuka, Takeshi; Ito, Norihiko; Imagawa, Tomohiro; Okamoto, Yoshiharu

    2016-01-01

    Canine mammary gland tumors (CMGTs), which are the most common neoplasms in sexually intact female dogs, have been suggested as a model for studying human breast cancer because of several similarities, including relative age of onset, risk factors, incidence, histological and molecular features, biological behavior, metastatic pattern, and responses to therapy. In the present study, we established a new cell line, the SNP cell line, from a CMGT. A tumor formed in each NOD.CB17-Prkdcscid/J mouse at the site of subcutaneous SNP cell injection. SNP cells are characterized by proliferation in a tubulopapillary pattern and are vimentin positive. Moreover, we examined miRNA expression in the cultured cells and found that the expression values of miRNA-143 and miRNA-138a showed the greatest increase and decrease, respectively, of all miRNAs observed, indicating that these miRNAs might play a significant role in the malignancy of SNP cells. Overall, the results of this study indicate that SNP cells might serve as a model for future genetic analysis and clinical treatments of human breast tumors. PMID:26726024

  13. Co-expressed miRNAs in gastric adenocarcinoma.

    PubMed

    Yepes, Sally; López, Rocío; Andrade, Rafael E; Rodriguez-Urrego, Paula A; López-Kleine, Liliana; Torres, Maria Mercedes

    2016-08-01

    Co-expression networks may provide insights into the patterns of molecular interactions that underlie cellular processes. To obtain a better understanding of miRNA expression patterns in gastric adenocarcinoma and to provide markers that can be associated with histopathological findings, we performed weighted gene correlation network analysis (WGCNA) and compare it with a supervised analysis. Integrative analysis of target predictions and miRNA expression profiles in gastric cancer samples was also performed. WGCNA identified a module of co-expressed miRNAs that were associated with histological traits and tumor condition. Hub genes were identified based on statistical analysis and network centrality. The miRNAs 100, let-7c, 125b and 99a stood out for their association with the diffuse histological subtype. The 181 miRNA family and miRNA 21 highlighted for their association with the tumoral phenotype. The integrated analysis of miRNA and gene expression profiles showed the let-7 miRNA family playing a central role in the regulatory relationships.

  14. miRNA Control of Tissue Repair and Regeneration

    PubMed Central

    Sen, Chandan K.; Ghatak, Subhadip

    2016-01-01

    Tissue repair and regeneration rely on the function of miRNA, molecular silencers that enact post-transcriptional gene silencing of coding genes. Disruption of miRNA homeostasis is developmentally lethal, indicating that fetal tissue development is tightly controlled by miRNAs. Multiple critical facets of adult tissue repair are subject to control by miRNAs, as well. Sources of cell pool for tissue repair and regeneration are diverse and provided by processes including cellular dedifferentiation, transdifferentiation, and reprogramming. Each of these processes is regulated by miRNAs. Furthermore, induced pluripotency may be achieved by miRNA-based strategies independent of transcription factor manipulation. The observation that miRNA does not integrate into the genome makes miRNA-based therapeutic strategies translationally valuable. Tools to manipulate cellular and tissue miRNA levels include mimics and inhibitors that may be specifically targeted to cells of interest at the injury site. Here, we discuss the extraordinary importance of miRNAs in tissue repair and regeneration based on emergent reports and rapid advances in miRNA-based therapeutics. PMID:26056933

  15. Localization and Sub-Cellular Shuttling of HTLV-1 Tax with the miRNA Machinery

    PubMed Central

    Van Duyne, Rachel; Guendel, Irene; Klase, Zachary; Narayanan, Aarthi; Coley, William; Jaworski, Elizabeth; Roman, Jessica; Popratiloff, Anastas; Mahieux, Renaud; Kehn-Hall, Kylene; Kashanchi, Fatah

    2012-01-01

    The innate ability of the human cell to silence endogenous retroviruses through RNA sequences encoding microRNAs, suggests that the cellular RNAi machinery is a major means by which the host mounts a defense response against present day retroviruses. Indeed, cellular miRNAs target and hybridize to specific sequences of both HTLV-1 and HIV-1 viral transcripts. However, much like the variety of host immune responses to retroviral infection, the virus itself contains mechanisms that assist in the evasion of viral inhibition through control of the cellular RNAi pathway. Retroviruses can hijack both the enzymatic and catalytic components of the RNAi pathway, in some cases to produce novel viral miRNAs that can either assist in active viral infection or promote a latent state. Here, we show that HTLV-1 Tax contributes to the dysregulation of the RNAi pathway by altering the expression of key components of this pathway. A survey of uninfected and HTLV-1 infected cells revealed that Drosha protein is present at lower levels in all HTLV-1 infected cell lines and in infected primary cells, while other components such as DGCR8 were not dramatically altered. We show colocalization of Tax and Drosha in the nucleus in vitro as well as coimmunoprecipitation in the presence of proteasome inhibitors, indicating that Tax interacts with Drosha and may target it to specific areas of the cell, namely, the proteasome. In the presence of Tax we observed a prevention of primary miRNA cleavage by Drosha. Finally, the changes in cellular miRNA expression in HTLV-1 infected cells can be mimicked by the add back of Drosha or the addition of antagomiRs against the cellular miRNAs which are downregulated by the virus. PMID:22808228

  16. The development and function of dendritic cell populations and their regulation by miRNAs.

    PubMed

    Zhou, Haibo; Wu, Li

    2017-03-31

    Dendritic cells (DCs) are important immune cells linking innate and adaptive immune responses. DCs encounter various self and non-self antigens present in the environment and induce different types of antigen specific adaptive immune responses. DCs can be classified into lymphoid tissue-resident DCs, migratory DCs, non-lymphoid resident DCs, and monocyte derived DCs (moDCs). Recent work has also established that DCs consist of developmentally and functionally distinct subsets that differentially regulate T lymphocyte function. The development of different DC subsets has been found to be regulated by a network of different cytokines and transcriptional factors. Moreover, the response of DC is tightly regulated to maintain the homeostasis of immune system. MicroRNAs (miRNAs) are an important class of cellular regulators that modulate gene expression and thereby influence cell fate and function. In the immune system, miRNAs act at checkpoints during hematopoietic development and cell subset differentiation, they modulate effector cell function, and are implicated in the maintenance of homeostasis. DCs are also regulated by miRNAs. In the past decade, much progress has been made to understand the role of miRNAs in regulating the development and function of DCs. In this review, we summarize the origin and distribution of different mouse DC subsets in both lymphoid and non-lymphoid tissues. The DC subsets identified in human are also described. Recent progress on the function of miRNAs in the development and activation of DCs and their functional relevance to autoimmune diseases are discussed.

  17. Current State of Agile User-Centered Design: A Survey

    NASA Astrophysics Data System (ADS)

    Hussain, Zahid; Slany, Wolfgang; Holzinger, Andreas

    Agile software development methods are quite popular nowadays and are being adopted at an increasing rate in the industry every year. However, these methods are still lacking usability awareness in their development lifecycle, and the integration of usability/User-Centered Design (UCD) into agile methods is not adequately addressed. This paper presents the preliminary results of a recently conducted online survey regarding the current state of the integration of agile methods and usability/UCD. A world wide response of 92 practitioners was received. The results show that the majority of practitioners perceive that the integration of agile methods with usability/UCD has added value to their adopted processes and to their teams; has resulted in the improvement of usability and quality of the product developed; and has increased the satisfaction of the end-users of the product developed. The top most used HCI techniques are low-fidelity prototyping, conceptual designs, observational studies of users, usability expert evaluations, field studies, personas, rapid iterative testing, and laboratory usability testing.

  18. Network configuration management : paving the way to network agility.

    SciTech Connect

    Maestas, Joseph H.

    2007-08-01

    Sandia networks consist of nearly nine hundred routers and switches and nearly one million lines of command code, and each line ideally contributes to the capabilities of the network to convey information from one location to another. Sandia's Cyber Infrastructure Development and Deployment organizations recognize that it is therefore essential to standardize network configurations and enforce conformance to industry best business practices and documented internal configuration standards to provide a network that is agile, adaptable, and highly available. This is especially important in times of constrained budgets as members of the workforce are called upon to improve efficiency, effectiveness, and customer focus. Best business practices recommend using the standardized configurations in the enforcement process so that when root cause analysis results in recommended configuration changes, subsequent configuration auditing will improve compliance to the standard. Ultimately, this minimizes mean time to repair, maintains the network security posture, improves network availability, and enables efficient transition to new technologies. Network standardization brings improved network agility, which in turn enables enterprise agility, because the network touches all facets of corporate business. Improved network agility improves the business enterprise as a whole.

  19. Tailoring Agility: Promiscuous Pair Story Authoring and Value Calculation

    NASA Astrophysics Data System (ADS)

    Tendon, Steve

    This chapter describes how a multi-national software organization created a business plan involving business units from eight countries that followed an agile way, after two previously failed attempts with traditional approaches. The case is told by the consultant who initiated implementation of agility into requirements gathering, estimation and planning processes in an international setting. The agile approach was inspired by XP, but then tailored to meet the peculiar requirements. Two innovations were critical. The first innovation was promiscuous pair story authoring, where user stories were written by two people (similarly to pair programming), and the pairing changed very often (as frequently as every 15-20 minutes) to achieve promiscuity and cater for diverse point of views. The second innovation was an economic value evaluation (and not the cost) which was attributed to stories. Continuous recalculation of the financial value of the stories allowed to assess the projects financial return. In this case implementation of agility in the international context allowed the involved team members to reach consensus and unanimity of decisions, vision and purpose.

  20. Considerations for Using Agile in DoD Acquisition

    DTIC Science & Technology

    2010-04-01

    Buettner, Aerospace Joe Tatem, Raytheon Stephany Bellomo, SEI Nanette Brown, SEI John Foreman, SEI Dr. John Goodenough, SEI Harry Levinson, SEI...event_details.php?id=452 [2] H. Glazer, J. Dalton, D. Anderson, M. Konrad , and S. Shrum, "CMMI or Agile: Why Not Embrace Both," Carnegie Mellon

  1. A Capstone Course on Agile Software Development Using Scrum

    ERIC Educational Resources Information Center

    Mahnic, V.

    2012-01-01

    In this paper, an undergraduate capstone course in software engineering is described that not only exposes students to agile software development, but also makes it possible to observe the behavior of developers using Scrum for the first time. The course requires students to work as Scrum Teams, responsible for the implementation of a set of user…

  2. Agile manufacturing and constraints management: a strategic perspective

    NASA Astrophysics Data System (ADS)

    Stratton, Roy; Yusuf, Yahaya Y.

    2000-10-01

    The definition of the agile paradigm has proved elusive and is often viewed as a panacea, in contention with more traditional approaches to operations strategy development and Larkin its own methodology and tools. The Theory of Constraints (TOC) is also poorly understood, as it is commonly solely associated with production planning and control systems and bottleneck management. This paper will demonstrate the synergy between these two approaches together with the Theory of Inventive Problem Solving (TRIZ), and establish how the systematic elimination of trade-offs can support the agile paradigm. Whereas agility is often seen as a trade-off free destination, both TOC and TRIZ may be considered to be route finders, as they comprise methodologies that focus on the identification and elimination of the trade-offs that constrain the purposeful improvement of a system, be it organizational or mechanical. This paper will also show how the TOC thinking process may be combined with the TRIZ knowledge based approach and used in breaking contradictions within agile logistics.

  3. Correlation between agility and sprinting according to student age.

    PubMed

    Yanci, Javier; Los Arcos, Asier; Grande, Ignacio; Gil, Eneko; Cámara, Jesús

    2014-06-01

    The purposes of the study were to assess sprinting and agility performance characteristics and to determine the relationship between these two motor skills in elementary education students. Sprinting and agility performance were assessed in 176 children (88 boys and 88 girls) divided into three groups: Group 1 (G1, N = 98; 48 boys and 50 girls), from the first year of elementary education; Group 2 (G2, N = 38; 15 boys and 23 girls), from the second year of elementary education; Group 3 (G3, N = 40; 25 boys and 15 girls), from the third year of elementary education. Significant differences (p < 0.001) were found in agility ability among the groups and between G1-G3 and G2-G3 in the 5 and 15 m sprint. Regarding gender of the students of the same age, significant differences (p < 0.001) between boys and girls in group G1 and G2 were obtained in the 5 and 15 m sprint. The correlation between agility and acceleration was significant but moderate (0.3 < r < 0.7) in all groups (G1, G2, and G3), in most cases. When the gender factor was included, the results were heterogeneous. Assessing this correlation according to age and gender produced heterogeneous results. For this reason, we think that both are independent qualities and that age and gender are two factors that influence the correlation results.

  4. Wavelength-Agile External-Cavity Diode Laser for DWDM

    NASA Technical Reports Server (NTRS)

    Pilgrim, Jeffrey S.; Bomse, David S.

    2006-01-01

    A prototype external-cavity diode laser (ECDL) has been developed for communication systems utilizing dense wavelength- division multiplexing (DWDM). This ECDL is an updated version of the ECDL reported in Wavelength-Agile External- Cavity Diode Laser (LEW-17090), NASA Tech Briefs, Vol. 25, No. 11 (November 2001), page 14a. To recapitulate: The wavelength-agile ECDL combines the stability of an external-cavity laser with the wavelength agility of a diode laser. Wavelength is modulated by modulating the injection current of the diode-laser gain element. The external cavity is a Littman-Metcalf resonator, in which the zeroth-order output from a diffraction grating is used as the laser output and the first-order-diffracted light is retro-reflected by a cavity feedback mirror, which establishes one end of the resonator. The other end of the resonator is the output surface of a Fabry-Perot resonator that constitutes the diode-laser gain element. Wavelength is selected by choosing the angle of the diffracted return beam, as determined by position of the feedback mirror. The present wavelength-agile ECDL is distinguished by design details that enable coverage of all 60 channels, separated by 100-GHz frequency intervals, that are specified in DWDM standards.

  5. Impact of Agile Software Development Model on Software Maintainability

    ERIC Educational Resources Information Center

    Gawali, Ajay R.

    2012-01-01

    Software maintenance and support costs account for up to 60% of the overall software life cycle cost and often burdens tightly budgeted information technology (IT) organizations. Agile software development approach delivers business value early, but implications on software maintainability are still unknown. The purpose of this quantitative study…

  6. Agile Software Development Methods: A Comparative Review1

    NASA Astrophysics Data System (ADS)

    Abrahamsson, Pekka; Oza, Nilay; Siponen, Mikko T.

    Although agile software development methods have caught the attention of software engineers and researchers worldwide, scientific research still remains quite scarce. The aim of this study is to order and make sense of the different agile approaches that have been proposed. This comparative review is performed from the standpoint of using the following features as the analytical perspectives: project management support, life-cycle coverage, type of practical guidance, adaptability in actual use, type of research objectives and existence of empirical evidence. The results show that agile software development methods cover, without offering any rationale, different phases of the software development life-cycle and that most of these methods fail to provide adequate project management support. Moreover, quite a few methods continue to offer little concrete guidance on how to use their solutions or how to adapt them in different development situations. Empirical evidence after ten years of application remains quite limited. Based on the results, new directions on agile methods are outlined.

  7. Agile Bodies: A New Imperative in Neoliberal Governance

    ERIC Educational Resources Information Center

    Gillies, Donald

    2011-01-01

    Modern business discourse suggests that a key bulwark against market fluctuation and the threat of failure is for organizations to become "agile'", a more dynamic and proactive position than that previously afforded by mere "flexibility". The same idea is also directed at the personal level, it being argued that the…

  8. miRNA Regulation of Immune Tolerance in Early Pregnancy.

    PubMed

    Schjenken, John E; Zhang, Bihong; Chan, Hon Y; Sharkey, David J; Fullston, Tod; Robertson, Sarah A

    2016-03-01

    To support embryo implantation, the female reproductive tract must provide a tolerogenic immune environment. Seminal fluid contact at conception contributes to activating the endometrial gene expression and immune cell changes required for robust implantation, influencing not only the quality of the ensuing pregnancy but also the health of offspring. miRNAs are small non-coding RNAs that play important regulatory roles in biological processes, including regulation of the immune environment. miRNAs are known to contribute to gene regulation in pregnancy and are altered in pregnancy pathologies. Recent studies indicate that miRNAs participate in establishing immune tolerance at conception, and may contribute to the regulatory effects of seminal fluid in generating tolerogenic dendritic cells and T regulatory cells. This review highlights those miRNAs implicated in programming immune cells that are critical during the peri-conception period and explores how seminal fluid may regulate female tract miRNA expression following coitus.

  9. Modulation of Host miRNAs by Intracellular Bacterial Pathogens

    PubMed Central

    Das, Kishore; Garnica, Omar; Dhandayuthapani, Subramanian

    2016-01-01

    MicroRNAs (miRNAs) are short non-coding RNAs that regulate the expression of protein coding genes of viruses and eukaryotes at the post-transcriptional level. The eukaryotic genes regulated by miRNAs include those whose products are critical for biological processes such as cell proliferation, metabolic pathways, immune response, and development. It is now increasingly recognized that modulation of miRNAs associated with biological processes is one of the strategies adopted by bacterial pathogens to survive inside host cells. In this review, we present an overview of the recent findings on alterations of miRNAs in the host cells by facultative intracellular bacterial pathogens. In addition, we discuss how the altered miRNAs help in the survival of these pathogens in the intracellular environment. PMID:27536558

  10. Sex-biased miRNAs in gonad and their potential roles for testis development in yellow catfish.

    PubMed

    Jing, Jing; Wu, Junjie; Liu, Wei; Xiong, Shuting; Ma, Wenge; Zhang, Jin; Wang, Weimin; Gui, Jian-Fang; Mei, Jie

    2014-01-01

    Recently, YY super-male yellow catfish had been created by hormonal-induced sex reversal and sex-linked markers, which provides a promising research model for fish sex differentiation and gonad development, especially for testis development. MicroRNAs (miRNAs) have been revealed to play crucial roles in the gene regulation and gonad development in vertebrates. In this study, three small RNA libraries constructed from gonad tissues of XX female, XY male and YY super-male yellow catfish were sequenced. The sequencing data generated a total of 384 conserved miRNAs and 113 potential novel miRNAs, among which 23, 30 and 14 miRNAs were specifically detected in XX ovary, XY testis, and YY testis, respectively. We observed relative lower expression of several miR-200 family members, including miR-141 and miR-429 in YY testis compared with XY testis. Histological analysis indicated a higher degree of testis maturity in YY super-males compared with XY males, as shown by larger spermatogenic cyst, more spermatids and fewer spermatocytes in the spermatogenic cyst. Moreover, five miR-200 family members were significantly up-regulated in testis when treated by 17α-ethinylestradiol (EE2), high dose of which will impair testis development and cell proliferation. The down-regulation of miR-141 and 429 coincides with the progression of testis development in both yellow catfish and human. At last, the expression pattern of nine arbitrarily selected miRNAs detected by quantitative RT-PCR was consistent with the Solexa sequencing results. Our study provides a comprehensive miRNA transcriptome analysis for gonad of yellow catfish with different sex genotypes, and identifies a number of sex-biased miRNAs, some of that are potentially involved in testis development and spermatogenesis.

  11. AGILE integration into APC for high mix logic fab

    NASA Astrophysics Data System (ADS)

    Gatefait, M.; Lam, A.; Le Gratiet, B.; Mikolajczak, M.; Morin, V.; Chojnowski, N.; Kocsis, Z.; Smith, I.; Decaunes, J.; Ostrovsky, A.; Monget, C.

    2015-09-01

    For C040 technology and below, photolithographic depth of focus control and dispersion improvement is essential to secure product functionality. Critical 193nm immersion layers present initial focus process windows close to machine control capability. For previous technologies, the standard scanner sensor (Level sensor - LS) was used to map wafer topology and expose the wafer at the right Focus. Such optical embedded metrology, based on light reflection, suffers from reading issues that cannot be neglected anymore. Metrology errors are correlated to inspected product area for which material types and densities change, and so optical properties are not constant. Various optical phenomena occur across the product field during wafer inspection and have an effect on the quality and position of the reflected light. This can result in incorrect heights being recorded and exposures possibly being done out of focus. Focus inaccuracy associated to aggressive process windows on critical layers will directly impact product realization and therefore functionality and yield. ASML has introduced an air gauge sensor to complement the optical level sensor and lead to optimal topology metrology. The use of this new sensor is managed by the AGILE (Air Gauge Improved process LEveling) application. This measurement with no optical dependency will correct for optical inaccuracy of level sensor, and so improve best focus dispersion across the product. Due to the fact that stack complexity is more and more important through process steps flow, optical perturbation of standard Level sensor metrology is increasing and is becoming maximum for metallization layers. For these reasons AGILE feature implementation was first considered for contact and all metal layers. Another key point is that standard metrology will be sensitive to layer and reticle/product density. The gain of Agile will be enhanced for multiple product contribution mask and for complex System on Chip. Into ST context (High

  12. Highly selective and sensitive detection of miRNA based on toehold-mediated strand displacement reaction and DNA tetrahedron substrate.

    PubMed

    Li, Wei; Jiang, Wei; Ding, Yongshun; Wang, Lei

    2015-09-15

    MicroRNAs (miRNAs) play important roles in a variety of biological processes and have been regarded as tumor biomarkers in cancer diagnosis and prognosis. In this work, a single-molecule counting method for miRNA analysis was proposed based on toehold-mediated strand displacement reaction (SDR) and DNA tetrahedron substrate. Firstly, a specially designed DNA tetrahedron was assembled with a hairpin at one of the vertex, which has an overhanging toehold domain. Then, the DNA tetrahedron was immobilized on the epoxy-functional glass slide by epoxy-amine reaction, forming a DNA tetrahedron substrate. Next, the target miRNA perhybridized with the toehold domain and initiated a strand displacement reaction along with the unfolding of the hairpin, realizing the selective recognization of miRNA. Finally, a biotin labeled detection DNA was hybridized with the new emerging single strand and the streptavidin coated QDs were used as fluorescent probes. Fluorescent images were acquired via epi-fluorescence microscopy, the numbers of fluorescence dots were counted one by one for quantification. The detection limit is 5 fM, which displayed an excellent sensitivity. Moreover, the proposed method which can accurately be identified the target miRNA among its family members, demonstrated an admirable selectivity. Furthermore, miRNA analysis in total RNA samples from human lung tissues was performed, suggesting the feasibility of this method for quantitative detection of miRNA in biomedical research and early clinical diagnostics.

  13. Screening on the differentially expressed miRNAs in zebrafish (Danio rerio) exposed to trace β-diketone antibiotics and their related functions.

    PubMed

    Li, Jieyi; Liu, Jinfeng; Zhang, Yuhuan; Wang, Xuedong; Li, Weijun; Zhang, Hongqin; Wang, Huili

    2016-09-01

    The toxicity of β-diketone antibiotics (DKAs) to larval and adult zebrafish (Danio rerio) was investigated by miRNA sequencing and bioinformatics analyses. In control and DKA-exposed groups, 215 differentially expressed miRNAs were screened, and 4076 differential target genes were predicted. Among 51 co-differentially expressed genes, 45 were annotated in KOG functional classification, and 34 in KEGG pathway analysis. The homology analysis of 20 miRNAs with human hsa-miRNAs demonstrated 17 high homologous sequences. The expression levels of 12 miRNAs by qRT-PCR were consistent with those by sRNA-seq. A regulatory network for 4 positive miRNA genes (dre-miR-10, -96, -92 and -184) was plotted, and the high-degree of connectivity between miRNA-gene pairs suggests that these miRNAs play critical roles during zebrafish development. The consistent expression of dre-miR-184 and dre-miR-96 was proved in 120-hpf zebrafish brain, gill, otoliths and lateral line neuromast by qRT-PCR, miRNA-seq, W-ISH and ISH. DKA-exposure led to vacuolation of interstitial cells, reduced number of neurons, glial cell proliferation and formation of glial scar, and the obvious abnormality of cell structure might result from abnormal expression of differentially expressed miRNAs. In general, chronic DKA-exposure resulted in comprehensively toxic effects on larval and adult zebrafish tissues, especially for nervous system.

  14. A Toolbox for Herpesvirus miRNA Research: Construction of a Complete Set of KSHV miRNA Deletion Mutants.

    PubMed

    Jain, Vaibhav; Plaisance-Bonstaff, Karlie; Sangani, Rajnikumar; Lanier, Curtis; Dolce, Alexander; Hu, Jianhong; Brulois, Kevin; Haecker, Irina; Turner, Peter; Renne, Rolf; Krueger, Brian

    2016-02-19

    Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 12 viral microRNAs (miRNAs) that are expressed during latency. Research into KSHV miRNA function has suffered from a lack of genetic systems to study viral miRNA mutations in the context of the viral genome. We used the Escherichia coli Red recombination system together with a new bacmid background, BAC16, to create mutants for all known KSHV miRNAs. The specific miRNA deletions or mutations and the integrity of the bacmids have been strictly quality controlled using PCR, restriction digestion, and sequencing. In addition, stable viral producer cell lines based on iSLK cells have been created for wildtype KSHV, for 12 individual miRNA knock-out mutants (ΔmiR-K12-1 through -12), and for mutants deleted for 10 of 12 (ΔmiR-cluster) or all 12 miRNAs (ΔmiR-all). NGS, in combination with SureSelect technology, was employed to sequence the entire latent genome within all producer cell lines. qPCR assays were used to verify the expression of the remaining viral miRNAs in a subset of mutants. Induction of the lytic cycle leads to efficient production of progeny viruses that have been used to infect endothelial cells. Wt BAC16 and miR mutant iSLK producer cell lines are now available to the research community.

  15. Integrating miRNA and mRNA Expression Profiling Uncovers miRNAs Underlying Fat Deposition in Sheep

    PubMed Central

    Zhou, Guangxian; Wang, Xiaolong; Yuan, Chao; Kang, Danju; Xu, Xiaochun; Zhou, Jiping; Geng, Rongqing; Yang, Yuxin; Yang, Zhaoxia

    2017-01-01

    MicroRNAs (miRNAs) are endogenous, noncoding RNAs that regulate various biological processes including adipogenesis and fat metabolism. Here, we adopted a deep sequencing approach to determine the identity and abundance of miRNAs involved in fat deposition in adipose tissues from fat-tailed (Kazakhstan sheep, KS) and thin-tailed (Tibetan sheep, TS) sheep breeds. By comparing HiSeq data of these two breeds, 539 miRNAs were shared in both breeds, whereas 179 and 97 miRNAs were uniquely expressed in KS and TS, respectively. We also identified 35 miRNAs that are considered to be putative novel miRNAs. The integration of miRNA-mRNA analysis revealed that miRNA-associated targets were mainly involved in the gene ontology (GO) biological processes concerning cellular process and metabolic process, and miRNAs play critical roles in fat deposition through their ability to regulate fundamental pathways. These pathways included the MAPK signaling pathway, FoxO and Wnt signaling pathway, and focal adhesion. Taken together, our results define miRNA expression signatures that may contribute to fat deposition and lipid metabolism in sheep. PMID:28293627

  16. Phytoalexins, miRNAs and breast cancer: a review of phytochemical mediated miRNA regulation in breast cancer

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A specific class of endogenous, non-coding RNAs, classified as microRNAs (miRNAs), has been identified. It has been found that miRNAs are associated with many biological processes and disease states, including all stages of cancer from initiation to tumor promotion and progression. These studies d...

  17. Integrating miRNA and mRNA Expression Profiling Uncovers miRNAs Underlying Fat Deposition in Sheep.

    PubMed

    Zhou, Guangxian; Wang, Xiaolong; Yuan, Chao; Kang, Danju; Xu, Xiaochun; Zhou, Jiping; Geng, Rongqing; Yang, Yuxin; Yang, Zhaoxia; Chen, Yulin

    2017-01-01

    MicroRNAs (miRNAs) are endogenous, noncoding RNAs that regulate various biological processes including adipogenesis and fat metabolism. Here, we adopted a deep sequencing approach to determine the identity and abundance of miRNAs involved in fat deposition in adipose tissues from fat-tailed (Kazakhstan sheep, KS) and thin-tailed (Tibetan sheep, TS) sheep breeds. By comparing HiSeq data of these two breeds, 539 miRNAs were shared in both breeds, whereas 179 and 97 miRNAs were uniquely expressed in KS and TS, respectively. We also identified 35 miRNAs that are considered to be putative novel miRNAs. The integration of miRNA-mRNA analysis revealed that miRNA-associated targets were mainly involved in the gene ontology (GO) biological processes concerning cellular process and metabolic process, and miRNAs play critical roles in fat deposition through their ability to regulate fundamental pathways. These pathways included the MAPK signaling pathway, FoxO and Wnt signaling pathway, and focal adhesion. Taken together, our results define miRNA expression signatures that may contribute to fat deposition and lipid metabolism in sheep.

  18. miRNA and mRNA expression analysis reveals potential sex-biased miRNA expression

    PubMed Central

    Guo, Li; Zhang, Qiang; Ma, Xiao; Wang, Jun; Liang, Tingming

    2017-01-01

    Recent studies suggest that mRNAs may be differentially expressed between males and females. This study aimed to perform expression analysis of mRNA and its main regulatory molecule, microRNA (miRNA), to discuss the potential sex-specific expression patterns using abnormal expression profiles from The Cancer Genome Atlas database. Generally, deregulated miRNAs and mRNAs had consistent expression between males and females, but some miRNAs may be oppositely expressed in specific diseases: up-regulated in one group and down-regulated in another. Studies of miRNA gene families and clusters further confirmed that these sequence or location related miRNAs might have opposing expression between sexes. The specific miRNA might have greater expression divergence across different groups, suggesting flexible expression across different individuals, especially in tumor samples. The typical analysis regardless of the sex will ignore or balance these sex-specific deregulated miRNAs. Compared with flexible miRNAs, their targets of mRNAs showed relative stable expression between males and females. These relevant results provide new insights into miRNA-mRNA interaction and sex difference. PMID:28045090

  19. Organizational Agility and Complex Enterprise System Innovations: A Mixed Methods Study of the Effects of Enterprise Systems on Organizational Agility

    ERIC Educational Resources Information Center

    Kharabe, Amol T.

    2012-01-01

    Over the last two decades, firms have operated in "increasingly" accelerated "high-velocity" dynamic markets, which require them to become "agile." During the same time frame, firms have increasingly deployed complex enterprise systems--large-scale packaged software "innovations" that integrate and automate…

  20. [The role of miRNA in endometrial cancer in the context of miRNA 205].

    PubMed

    Wilczyński, Miłosz; Danielska, Justyna; Dzieniecka, Monika; Malinowski, Andrzej

    2015-11-01

    MiRNAs are small, non-coding molecules of ribonucleic acids of approximately 22 bp length, which serve as regulators of gene expression and protein translation due to interference with messenger RNA (mRNA). MiRNAs, which take part in the regulation of cell cycle and apoptosis, may be associated with carcinogenesis. Aberrant expression of miRNAs in endometrial cancer might contribute to the endometrial cancer initiation or progression, as well as metastasis formation, and may influence cancer invasiveness. Specific-miRNAs expressed in endometrial cancer tissues may serve as diagnostic markers of the disease, prognostic biomarkers, or play an important part in oncological therapy We aimed to describe the role of miRNAs in endometrial cancer with special consideration of miRNA 205.

  1. GeneSet2miRNA: finding the signature of cooperative miRNA activities in the gene lists

    PubMed Central

    Antonov, Alexey V.; Dietmann, Sabine; Wong, Philip; Lutter, Dominik; Mewes, Hans W.

    2009-01-01

    GeneSet2miRNA is the first web-based tool which is able to identify whether or not a gene list has a signature of miRNA-regulatory activity. As input, GeneSet2miRNA accepts a list of genes. As output, a list of miRNA-regulatory models is provided. A miRNA-regulatory model is a group of miRNAs (single, pair, triplet or quadruplet) that is predicted to regulate a significant subset of genes from the submitted list. GeneSet2miRNA provides a user friendly dialog-driven web page submission available for several model organisms. GeneSet2miRNA is freely available at http://mips.helmholtz-muenchen.de/proj/gene2mir/. PMID:19420064

  2. Quantification of circulating miRNAs by droplet digital PCR: comparison of EvaGreen- and TaqMan-based chemistries.

    PubMed

    Miotto, Elena; Saccenti, Elena; Lupini, Laura; Callegari, Elisa; Negrini, Massimo; Ferracin, Manuela

    2014-12-01

    Droplet digital PCR (ddPCR) has been successfully used with TaqMan assays to assess gene expression through the quantification of mRNA and miRNA. Recently, a new ddPCR system that can also run DNA-binding dye-based assays has been developed but it has not yet been tested for miRNA. We tested and compared the feasibility of quantifying miRNA with the new QX200 Droplet Digital PCR system when used with EvaGreen dye- and TaqMan probe-based assays. RNA from plasma and serum of 28 patients with cancer and healthy persons was reverse-transcribed and quantified for two circulating miRNAs and one added exogenous miRNA, with both EvaGreen dye-based miRCURY LNA miRNA assays and TaqMan assays. Amplification and detection of target miRNAs were performed on the QX200 ddPCR system. Conditions required to run miRCURY LNA miRNA assays were optimized. The EvaGreen-based assay was precise, reproducible over a range of concentrations of four orders of magnitude, and sensitive, detecting a target miRNA at levels down to 1 copy/μL. When this assay was compared with TaqMan assays, high concordance was obtained for two endogenous miRNAs in serum and plasma (Pearson r > 0.90). EvaGreen dye-based and TaqMan probe-based assays can be equally used with the ddPCR system to quantify circulating miRNAs in human plasma and serum. This study establishes the basis for using EvaGreen dye-based assays on a ddPCR system for quantifying circulating miRNA biomarkers and potentially other low-abundance RNA biomarkers in human biofluids. See all the articles in this CEBP Focus section, "Biomarkers, Biospecimens, and New Technologies in Molecular Epidemiology."

  3. Sensitive electrochemical determination of miRNAs based on a sandwich assay onto magnetic microcarriers and hybridization chain reaction amplification.

    PubMed

    Torrente-Rodríguez, R M; Campuzano, S; Montiel, V Ruiz-Valdepeñas; Montoya, J J; Pingarrón, J M

    2016-12-15

    A novel electrochemical approach for determination of miRNAs involving a sandwich hybridization assay onto streptavidin-magnetic beads (Strep-MBs), hybridization chain reaction (HCR) amplification and amperometric detection at disposable screen-printed carbon electrodes is reported. Using miRNA-21 as the target analyte, a dynamic linear range from 0.2 to 5.0nM with a 60pM (1.5fmol in 25μL) detection limit was obtained. The achieved sensitivity is 24-fold higher than a non-HCR amplification approach involving conventional sandwich type assay onto MBs. Moreover, the whole assay time lasted 1h 45min which is remarkably shorter than other reported methodologies. The methodology exhibited full selectivity against other non-complementary miRNAs as well as an acceptable discrimination between homologous miRNA family members. The applicability of this novel approach was demonstrated by determining mature miRNA-21 in total RNA (RNAt) extracted from tumor cells and human tissues.

  4. Effect of salts, solvents and buffer on miRNA detection using DNA silver nanocluster (DNA/AgNCs) probes

    NASA Astrophysics Data System (ADS)

    Shah, Pratik; Cho, Seok Keun; Waaben Thulstrup, Peter; Bhang, Yong-Joo; Ahn, Jong Cheol; Choi, Suk Won; Rørvig-Lund, Andreas; Yang, Seong Wook

    2014-01-01

    MicroRNAs (miRNAs) are small regulatory RNAs (size ˜21 nt to ˜25 nt) which regulate a variety of important cellular events in plants, animals and single cell eukaryotes. Especially because of their use in diagnostics of human diseases, efforts have been directed towards the invention of a rapid, simple and sequence selective detection method for miRNAs. Recently, we reported an innovative method for the determination of miRNA levels using the red fluorescent properties of DNA/silver nanoclusters (DNA/AgNCs). Our method is based on monitoring the emission drop of a DNA/AgNCs probe in the presence of its specific target miRNA. Accordingly, the accuracy and efficiency of the method relies on the sensitivity of hybridization between the probe and target. To gain specific and robust hybridization between probe and target, we investigated a range of diverse salts, organic solvents, and buffer to optimize target sensing conditions. Under the newly adjusted conditions, the target sensitivity and the formation of emissive DNA/AgNCs probes were significantly improved. Also, fortification of the Tris-acetate buffer with inorganic salts or organic solvents improved the sensitivity of the DNA/AgNC probes. On the basis of these optimizations, the versatility of the DNA/AgNCs-based miRNA detection method can be expanded.

  5. A miRNA-tRNA mix-up: tRNA origin of proposed miRNA.

    PubMed

    Schopman, Nick C T; Heynen, Stephan; Haasnoot, Joost; Berkhout, Ben

    2010-01-01

    The rapid release of new data from DNA genome sequencing projects has led to a variety of misannotations in public databases. Our results suggest that next generation sequencing approaches are particularly prone to such misannotations. Two related miRNA candidates did recently enter the miRBase database, miR-1274b and miR-1274a, but they share identical 18-nucleotide stretches with tRNA (Lys3) and tRNA (Lys5) , respectively. The possibility that the small RNA fragments that led to the description of these two miRNAs originated from the two tRNAs was examined. The ratio of the miR-1274b:miR-1274a fragments does closely resemble the known tRNA lys3:lys5 ratio in the cell. Furthermore, the proposed miRNA hairpins have a very low prediction score and the proposed miRNA genes are in fact endogenous retroviral elements. We searched for other miRNA-mimics in the human genome and found more examples of tRNA-miRNA mimicry. We propose that the corresponding miRNAs should be validated in more detail, as the small RNA fragments that led to their description are likely derived from tRNA processing.

  6. The Epstein-Barr Virus BART miRNA Cluster of the M81 Strain Modulates Multiple Functions in Primary B Cells

    PubMed Central

    Lin, Xiaochen; Tsai, Ming-Han; Shumilov, Anatoliy; Poirey, Remy; Bannert, Helmut; Middeldorp, Jaap M.; Feederle, Regina; Delecluse, Henri-Jacques

    2015-01-01

    The Epstein-Barr virus (EBV) is a B lymphotropic virus that infects the majority of the human population. All EBV strains transform B lymphocytes, but some strains, such as M81, also induce spontaneous virus replication. EBV encodes 22 microRNAs (miRNAs) that form a cluster within the BART region of the virus and have been previously been found to stimulate tumor cell growth. Here we describe their functions in B cells infected by M81. We found that the BART miRNAs are downregulated in replicating cells, and that exposure of B cells in vitro or in vivo in humanized mice to a BART miRNA knockout virus resulted in an increased proportion of spontaneously replicating cells, relative to wild type virus. The BART miRNAs subcluster 1, and to a lesser extent subcluster 2, prevented expression of BZLF1, the key protein for initiation of lytic replication. Thus, multiple BART miRNAs cooperate to repress lytic replication. The BART miRNAs also downregulated pro- and anti-apoptotic mediators such as caspase 3 and LMP1, and their deletion did not sensitize B-cells to apoptosis. To the contrary, the majority of humanized mice infected with the BART miRNA knockout mutant developed tumors more rapidly, probably due to enhanced LMP1 expression, although deletion of the BART miRNAs did not modify the virus transforming abilities in vitro. This ability to slow cell growth could be confirmed in non-humanized immunocompromized mice. Injection of resting B cells exposed to a virus that lacks the BART miRNAs resulted in accelerated tumor growth, relative to wild type controls. Therefore, we found that the M81 BART miRNAs do not enhance B-cell tumorigenesis but rather repress it. The repressive effects of the BART miRNAs on potentially pathogenic viral functions in infected B cells are likely to facilitate long-term persistence of the virus in the infected host. PMID:26694854

  7. In silico genome wide mining of conserved and novel miRNAs in the brain and pineal gland of Danio rerio using small RNA sequencing data.

    PubMed

    Agarwal, Suyash; Nagpure, Naresh Sahebrao; Srivastava, Prachi; Kushwaha, Basdeo; Kumar, Ravindra; Pandey, Manmohan; Srivastava, Shreya

    2016-03-01

    MicroRNAs (miRNAs) are small, non-coding RNA molecules that bind to the mRNA of the target genes and regulate the expression of the gene at the post-transcriptional level. Zebrafish is an economically important freshwater fish species globally considered as a good predictive model for studying human diseases and development. The present study focused on uncovering known as well as novel miRNAs, target prediction of the novel miRNAs and the differential expression of the known miRNA using the small RNA sequencing data of the brain and pineal gland (dark and light treatments) obtained from NCBI SRA. A total of 165, 151 and 145 known zebrafish miRNAs were found in the brain, pineal gland (dark treatment) and pineal gland (light treatment), respectively. Chromosomes 4 and 5 of zebrafish reference assembly GRCz10 were found to contain maximum number of miR genes. The miR-181a and miR-182 were found to be highly expressed in terms of number of reads in the brain and pineal gland, respectively. Other ncRNAs, such as tRNA, rRNA and snoRNA, were curated against Rfam. Using GRCz10 as reference, the subsequent bioinformatic analyses identified 25, 19 and 9 novel miRNAs from the brain, pineal gland (dark treatment) and pineal gland (light treatment), respectively. Targets of the novel miRNAs were identified, based on sequence complementarity between miRNAs and mRNA, by searching for antisense hits in the 3'-UTR of reference RNA sequences of the zebrafish. The discovery of novel miRNAs and their targets in the zebrafish genome can be a valuable scientific resource for further functional studies not only in zebrafish but also in other economically important fishes.

  8. Profiles of extracellular miRNA in cerebrospinal fluid and serum from patients with Alzheimer's and Parkinson's diseases correlate with disease status and features of pathology.

    PubMed

    Burgos, Kasandra; Malenica, Ivana; Metpally, Raghu; Courtright, Amanda; Rakela, Benjamin; Beach, Thomas; Shill, Holly; Adler, Charles; Sabbagh, Marwan; Villa, Stephen; Tembe, Waibhav; Craig, David; Van Keuren-Jensen, Kendall

    2014-01-01

    The discovery and reliable detection of markers for neurodegenerative diseases have been complicated by the inaccessibility of the diseased tissue--such as the inability to biopsy or test tissue from the central nervous system directly. RNAs originating from hard to access tissues, such as neurons within the brain and spinal cord, have the potential to get to the periphery where they can be detected non-invasively. The formation and extracellular release of microvesicles and RNA binding proteins have been found to carry RNA from cells of the central nervous system to the periphery and protect the RNA from degradation. Extracellular miRNAs detectable in peripheral circulation can provide information about cellular changes associated with human health and disease. In order to associate miRNA signals present in cell-free peripheral biofluids with neurodegenerative disease status of patients with Alzheimer's and Parkinson's diseases, we assessed the miRNA content in cerebrospinal fluid and serum from postmortem subjects with full neuropathology evaluations. We profiled the miRNA content from 69 patients with Alzheimer's disease, 67 with Parkinson's disease and 78 neurologically normal controls using next generation small RNA sequencing (NGS). We report the average abundance of each detected miRNA in cerebrospinal fluid and in serum and describe 13 novel miRNAs that were identified. We correlated changes in miRNA expression with aspects of disease severity such as Braak stage, dementia status, plaque and tangle densities, and the presence and severity of Lewy body pathology. Many of the differentially expressed miRNAs detected in peripheral cell-free cerebrospinal fluid and serum were previously reported in the literature to be deregulated in brain tissue from patients with neurodegenerative disease. These data indicate that extracellular miRNAs detectable in the cerebrospinal fluid and serum are reflective of cell-based changes in pathology and can be used to assess

  9. Protocol for miRNA isolation from biofluids.

    PubMed

    Lekchnov, Evgeny A; Zaporozhchenko, Ivan A; Morozkin, Evgeny S; Bryzgunova, Olga E; Vlassov, Valentin V; Laktionov, Pavel P

    2016-04-15

    MicroRNAs (miRNAs) have been identified as promising biomarkers in cancer and other diseases. Packaging of miRNAs into vesicles and complexes with proteins ensures their stability in biological fluids but also complicates their isolation. Conventional protocols used to isolate cell-free RNA are generally successful in overcoming these difficulties; however, they are costly, labor-intensive, or heavily reliant on the use of hazardous chemicals. Here we describe a protocol that is suitable for isolating miRNAs from biofluids, including blood plasma and urine. The protocol is based on precipitation of proteins, denaturation of miRNA-containing complexes with octanoic acid and guanidine isothiocyanate, and subsequent purification of miRNA on spin columns. The efficacy of miRNA extraction by phenol-chloroform extraction, miRCURY RNA isolation kit--biofluids (Exiqon), and the proposed protocol was compared by quantitative reverse-transcription PCR of miR-16 and miR-126. The proposed protocol was slightly more effective for isolating miRNA from plasma and significantly superior to the other two methods for miRNA isolation from urine. Spectrophotometry and SDS-PAGE data suggest that the disparity in performance between miRCURY Biofluids and the proposed protocol can be attributed to differences in precipitation mechanisms, as confirmed by the retention of different proteins in the supernatant.

  10. Investigation of key miRNAs and target genes in bladder cancer using miRNA profiling and bioinformatic tools.

    PubMed

    Canturk, Kemal Murat; Ozdemir, Muhsin; Can, Cavit; Öner, Setenay; Emre, Ramazan; Aslan, Huseyin; Cilingir, Oguz; Ciftci, Evrim; Celayir, Fatih Mehmet; Aldemir, Ozgur; Özen, Mustafa; Artan, Sevilhan

    2014-12-01

    Despite the association of several miRNAs with bladder cancer, little is known about the miRNAs' regulatory networks. In this study, we aimed to construct potential networks of bladder-cancer-related miRNAs and their known target genes using miRNA expression profiling and bioinformatics tools and to investigate potential key molecules that might play roles in bladder cancer regulatory networks. Global miRNA expression profiles were obtained using microarray followed by RT-qPCR validation using two randomly selected miRNAs. Known targets of deregulated miRNAs were utilized using DIANA-TarBase database v6.0. The incorporation of deregulated miRNAs and target genes into KEGG pathways were utilized using DIANA-mirPath software. To construct potential miRNA regulatory networks, the overlapping parts of three selected KEGG pathways were visualized by Cytoscape software. We finally gained 19 deregulated miRNAs, including 5 ups- and 14 down regulated in 27 bladder-cancer tissue samples and 8 normal urothelial tissue samples. The enrichment results of deregulated miRNAs and known target genes showed that most pathways were related to cancer or cell signaling pathways. We determined the hub CDK6, BCL2, E2F3, PTEN, MYC, RB, and ERBB3 target genes and hub hsa-let-7c, hsa-miR-195-5p, hsa-miR-141-3p, hsa-miR-26a-5p, hsa-miR-23b-3p, and hsa-miR-125b-5p miRNAs of the constructed networks. These findings provide new insights into the bladder cancer regulatory networks and give us a hypothesis that hsa-let-7c, hsa-miR-195-5p, and hsa-miR-125b-5p, along with CDK4 and CDK6 genes might exist in the same bladder cancer pathway. Particularly, hub miRNAs and genes might be potential biomarkers for bladder cancer clinics.

  11. miRNA Expression Profiles of HPV-Infected Patients with Cervical Cancer in the Uyghur Population in China.

    PubMed

    Gao, Dongmei; Zhang, Yuanyuan; Zhu, Mingyue; Liu, Shuang; Wang, Xinling

    2016-01-01

    The study aimed to investigate the state of human papillomavirus (HPV) infection in patients with cervical cancer in the Uyghur population in China and to identify miRNA as biomarker for cervical cancer and HPV infection. We also performed genotyping to determine the variation in the types of HPV. Using microRNA (miRNA) microarray technology, differential miRNA expression between HPV-infected cervical cancer and uninfected normal cervical tissues was determined; the microarray results were verified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) using 20 samples of both the tissues. The infection rate of HPV in patients with cervical cancer was 96.7% (29 of 30), and the main subtype identified was HPV16 (29 of 29). HPV16 integration assay demonstrated that the majority of infectious cases were of the integrated form (26 of 29). Analysis of 140 miRNAs demonstrated greater than two-fold change in miRNA expression in HPV-infected cervical cancer tissue as compared to that in uninfected cervical tissue. The qRT-PCR analysis verified that the expression of miR-15a-5p, miR-17-5p, miR-20a-5p, miR-21-5p, miR-96, miR-106b-5p, and miR-3653 was higher, while the expression of miR-497-5p was lower in cancer tissues than in normal tissues. The results demonstrate significant changes in miRNA expression in cervical cancer tissues associated with HPV infection as compared to that in normal tissues. These molecular markers may be useful for an early diagnosis and prognosis of cervical cancer in specific human populations.

  12. miRNA Involved in Six1-Induced Breast Cancer

    DTIC Science & Technology

    2013-05-01

    Summay 3. DATES COVERED 15 April 2010 – 14 April 2013 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER miRNA Involved in Six1-Induced Breast Cancer ...the cell cycle inhibitor, p21, and pro-apoptotic factor , Bim. These data suggest that Six1-induced upregulation of these miRNA may mediate the switch...promoting the pro-metastatic functions. 15. SUBJECT TERMS Six1, miRNAs , miR106b-25, TGFβ , epithelial to mesenchymal transition (EMT), cancer stem cells

  13. Dicer1-mediated miRNA processing shapes the mRNA profile and function of murine platelets.

    PubMed

    Rowley, Jesse W; Chappaz, Stéphane; Corduan, Aurélie; Chong, Mark M W; Campbell, Robert; Khoury, Amanda; Manne, Bhanu Kanth; Wurtzel, Jeremy G T; Michael, James V; Goldfinger, Lawrence E; Mumaw, Michele M; Nieman, Marvin T; Kile, Benjamin T; Provost, Patrick; Weyrich, Andrew S

    2016-04-07

    Human platelets contain microRNAs (miRNAs) and miRNA processing machinery, but their contribution to platelet function remains incompletely understood. Here, we show that murine megakaryocyte (MK)-specific knockdown of Dicer1, the ribonuclease that cleaves miRNA precursors into mature miRNAs, reduces the level of the majority of miRNAs in platelets. This leads to altered platelet messenger RNA (mRNA) expression profiles and mild thrombocytopenia. Fibrinogen receptor subunits Itga2b (αIIb) and Itgb3 (β3) mRNAs were among the differentially expressed transcripts that are increased in platelets lacking Dicer1. Argonaute 2 (Ago2), a member of the miRNA silencing complex, co-immunoprecipitated with αIIband β3mRNAs in wild-type platelets. Furthermore, co-immunoprecipitation experiments suggested reduced αIIb/β3/Ago2 complexes in miRNA-deficient platelets. These results suggested that miRNAs regulate both integrin subunits. Subsequent 3' untranslated region luciferase reporter assays confirmed that the translation of both αIIband β3mRNAs can be regulated by miRNAs miR-326, miR-128, miR-331, and miR-500. Consistent with these molecular changes, the deletion ofDicer1resulted in increased surface expression of integrins αIIband β3, and enhanced platelet binding to fibrinogen in vivo and in vitro. Heightened platelet reactivity, shortened tail-bleeding time, and reduced survival following collagen/epinephrine-induced pulmonary embolism were also observed in Dicer1-deficient animals. CombinedPf4-cre-mediated deletion of Drosha and Dicer1 did not significantly exacerbate phenotypes observed in single Dicer1 knockout mice. In summary, these findings indicate that Dicer1-dependent generation of mature miRNAs in late-stage MKs and platelets modulates the expression of target mRNAs important for the hemostatic and thrombotic function of platelets.

  14. Dicer1-mediated miRNA processing shapes the mRNA profile and function of murine platelets

    PubMed Central

    Chappaz, Stéphane; Corduan, Aurélie; Chong, Mark M. W.; Campbell, Robert; Khoury, Amanda; Manne, Bhanu Kanth; Wurtzel, Jeremy G. T.; Michael, James V.; Goldfinger, Lawrence E.; Mumaw, Michele M.; Nieman, Marvin T.; Kile, Benjamin T.; Provost, Patrick; Weyrich, Andrew S.

    2016-01-01

    Human platelets contain microRNAs (miRNAs) and miRNA processing machinery, but their contribution to platelet function remains incompletely understood. Here, we show that murine megakaryocyte (MK)-specific knockdown of Dicer1, the ribonuclease that cleaves miRNA precursors into mature miRNAs, reduces the level of the majority of miRNAs in platelets. This leads to altered platelet messenger RNA (mRNA) expression profiles and mild thrombocytopenia. Fibrinogen receptor subunits Itga2b (αIIb) and Itgb3 (β3) mRNAs were among the differentially expressed transcripts that are increased in platelets lacking Dicer1. Argonaute 2 (Ago2), a member of the miRNA silencing complex, co-immunoprecipitated with αIIb and β3 mRNAs in wild-type platelets. Furthermore, co-immunoprecipitation experiments suggested reduced αIIb/β3/Ago2 complexes in miRNA-deficient platelets. These results suggested that miRNAs regulate both integrin subunits. Subsequent 3′ untranslated region luciferase reporter assays confirmed that the translation of both αIIb and β3 mRNAs can be regulated by miRNAs miR-326, miR-128, miR-331, and miR-500. Consistent with these molecular changes, the deletion of Dicer1 resulted in increased surface expression of integrins αIIb and β3, and enhanced platelet binding to fibrinogen in vivo and in vitro. Heightened platelet reactivity, shortened tail-bleeding time, and reduced survival following collagen/epinephrine-induced pulmonary embolism were also observed in Dicer1-deficient animals. Combined Pf4-cre–mediated deletion of Drosha and Dicer1 did not significantly exacerbate phenotypes observed in single Dicer1 knockout mice. In summary, these findings indicate that Dicer1-dependent generation of mature miRNAs in late-stage MKs and platelets modulates the expression of target mRNAs important for the hemostatic and thrombotic function of platelets. PMID:26773046

  15. Targeting oncomiRNAs and mimicking tumor suppressor miRNAs: New trends in the development of miRNA therapeutic strategies in oncology (Review)

    PubMed Central

    GAMBARI, ROBERTO; BROGNARA, ELEONORA; SPANDIDOS, DEMETRIOS A.; FABBRI, ENRICA

    2016-01-01

    MicroRNA (miRNA or miR) therapeutics in cancer are based on targeting or mimicking miRNAs involved in cancer onset, progression, angiogenesis, epithelial-mesenchymal transition and metastasis. Several studies conclusively have demonstrated that miRNAs are deeply involved in tumor onset and progression, either behaving as tumor-promoting miRNAs (oncomiRNAs and metastamiRNAs) or as tumor suppressor miRNAs. This review focuses on the most promising examples potentially leading to the development of anticancer, miRNA-based therapeutic protocols. The inhibition of miRNA activity can be readily achieved by the use of miRNA inhibitors and oligomers, including RNA, DNA and DNA analogues (miRNA antisense therapy), small molecule inhibitors, miRNA sponges or through miRNA masking. On the contrary, the enhancement of miRNA function (miRNA replacement therapy) can be achieved by the use of modified miRNA mimetics, such as plasmid or lentiviral vectors carrying miRNA sequences. Combination strategies have been recently developed based on the observation that i) the combined administration of different antagomiR molecules induces greater antitumor effects and ii) some anti-miR molecules can sensitize drug-resistant tumor cell lines to therapeutic drugs. In this review, we discuss two additional issues: i) the combination of miRNA replacement therapy with drug administration and ii) the combination of antagomiR and miRNA replacement therapy. One of the solid results emerging from different independent studies is that miRNA replacement therapy can enhance the antitumor effects of the antitumor drugs. The second important conclusion of the reviewed studies is that the combination of anti-miRNA and miRNA replacement strategies may lead to excellent results, in terms of antitumor effects. PMID:27175518

  16. Between Oais and Agile a Dynamic Data Management Approach

    NASA Astrophysics Data System (ADS)

    Bennett, V. L.; Conway, E. A.; Waterfall, A. M.; Pepler, S.

    2015-12-01

    In this paper we decribe an approach to the integration of existing archival activities which lies between compliance with the more rigid OAIS/TRAC standards and a more flexible "Agile" approach to the curation and preservation of Earth Observation data. We provide a high level overview of existing practice and discuss how these procedures can be extended and supported through the description of preservation state. The aim of which is to facilitate the dynamic controlled management of scientific data through its lifecycle. While processes are considered they are not statically defined but rather driven by human interactions in the form of risk management/review procedure that produce actionable plans, which are responsive to change. We then proceed by describing the feasibility testing of extended risk management and planning procedures which integrate current practices. This was done through the CEDA Archival Format Audit which inspected British Atmospheric Data Centre and NERC Earth Observation Data Centre Archival holdings. These holdings are extensive, comprising of around 2 Petabytes of data and 137 million individual files, which were analysed and characterised in terms of format, based risk. We are then able to present an overview of the format based risk burden faced by a large scale archive attempting to maintain the usability of heterogeneous environmental data sets We continue by presenting a dynamic data management information model and provide discussion of the following core model entities and their relationships: Aspirational entities, which include Data Entity definitions and their associated Preservation Objectives. Risk entities, which act as drivers for change within the data lifecycle. These include Acquisitional Risks, Technical Risks, Strategic Risks and External Risks Plan entities, which detail the actions to bring about change within an archive. These include Acquisition Plans, Preservation Plans and Monitoring plans which support

  17. Identification of targets of miRNA-221 and miRNA-222 in fulvestrant-resistant breast cancer

    PubMed Central

    Liu, Pengfei; Sun, Manna; Jiang, Wenhua; Zhao, Jinkun; Liang, Chunyong; Zhang, Huilai

    2016-01-01

    The present study aimed to identify the differentially expressed genes (DEGs) regulated by microRNA (miRNA)-221 and miRNA-222 that are associated with the resistance of breast cancer to fulvestrant. The GSE19777 transcription profile was downloaded from the Gene Expression Omnibus database, and includes data from three samples of antisense miRNA-221-transfected fulvestrant-resistant MCF7-FR breast cancer cells, three samples of antisense miRNA-222-transfected fulvestrant-resistant MCF7-FR cells and three samples of control inhibitor (green fluorescent protein)-treated fulvestrant-resistant MCF7-FR cells. The linear models for microarray data package in R/Bioconductor was employed to screen for DEGs in the miRNA-transfected cells, and the pheatmap package in R was used to perform two-way clustering. Pathway enrichment was conducted using the Gene Set Enrichment Analysis tool. Furthermore, a miRNA-messenger (m) RNA regulatory network depicting interactions between miRNA-targeted upregulated DEGs was constructed and visualized using Cytoscape. In total, 492 and 404 DEGs were identified for the antisense miRNA-221-transfected MCF7-FR cells and the antisense miRNA-222-transfected MCF7-FR cells, respectively. Genes of the pentose phosphate pathway (PPP) were significantly enriched in the antisense miRNA-221-transfected MCF7-FR cells. In addition, components of the Wnt signaling pathway and cell adhesion molecules (CAMs) were significantly enriched in the antisense miRNA-222-transfected MCF7-FR cells. In the miRNA-mRNA regulatory network, miRNA-222 was demonstrated to target protocadherin 10 (PCDH10). The results of the present study suggested that the PPP and Wnt signaling pathways, as well as CAMs and PCDH10, may be associated with the resistance of breast cancer to fulvestrant. PMID:27895744

  18. Identification of targets of miRNA-221 and miRNA-222 in fulvestrant-resistant breast cancer.

    PubMed

    Liu, Pengfei; Sun, Manna; Jiang, Wenhua; Zhao, Jinkun; Liang, Chunyong; Zhang, Huilai

    2016-11-01

    The present study aimed to identify the differentially expressed genes (DEGs) regulated by microRNA (miRNA)-221 and miRNA-222 that are associated with the resistance of breast cancer to fulvestrant. The GSE19777 transcription profile was downloaded from the Gene Expression Omnibus database, and includes data from three samples of antisense miRNA-221-transfected fulvestrant-resistant MCF7-FR breast cancer cells, three samples of antisense miRNA-222-transfected fulvestrant-resistant MCF7-FR cells and three samples of control inhibitor (green fluorescent protein)-treated fulvestrant-resistant MCF7-FR cells. The linear models for microarray data package in R/Bioconductor was employed to screen for DEGs in the miRNA-transfected cells, and the pheatmap package in R was used to perform two-way clustering. Pathway enrichment was conducted using the Gene Set Enrichment Analysis tool. Furthermore, a miRNA-messenger (m) RNA regulatory network depicting interactions between miRNA-targeted upregulated DEGs was constructed and visualized using Cytoscape. In total, 492 and 404 DEGs were identified for the antisense miRNA-221-transfected MCF7-FR cells and the antisense miRNA-222-transfected MCF7-FR cells, respectively. Genes of the pentose phosphate pathway (PPP) were significantly enriched in the antisense miRNA-221-transfected MCF7-FR cells. In addition, components of the Wnt signaling pathway and cell adhesion molecules (CAMs) were significantly enriched in the antisense miRNA-222-transfected MCF7-FR cells. In the miRNA-mRNA regulatory network, miRNA-222 was demonstrated to target protocadherin 10 (PCDH10). The results of the present study suggested that the PPP and Wnt signaling pathways, as well as CAMs and PCDH10, may be associated with the resistance of breast cancer to fulvestrant.

  19. Agile development of ontologies through conversation

    NASA Astrophysics Data System (ADS)

    Braines, Dave; Bhattal, Amardeep; Preece, Alun D.; de Mel, Geeth

    2016-05-01

    Ontologies and semantic systems are necessarily complex but offer great potential in terms of their ability to fuse information from multiple sources in support of situation awareness. Current approaches do not place the ontologies directly into the hands of the end user in the field but instead hide them away behind traditional applications. We have been experimenting with human-friendly ontologies and conversational interactions to enable non-technical business users to interact with and extend these dynamically. In this paper we outline our approach via a worked example, covering: OWL ontologies, ITA Controlled English, Sensor/mission matching and conversational interactions between human and machine agents.

  20. Agile Data Management with the Global Change Information System

    NASA Astrophysics Data System (ADS)

    Duggan, B.; Aulenbach, S.; Tilmes, C.; Goldstein, J.

    2013-12-01

    We describe experiences applying agile software development techniques to the realm of data management during the development of the Global Change Information System (GCIS), a web service and API for authoritative global change information under development by the US Global Change Research Program. Some of the challenges during system design and implementation have been : (1) balancing the need for a rigorous mechanism for ensuring information quality with the realities of large data sets whose contents are often in flux, (2) utilizing existing data to inform decisions about the scope and nature of new data, and (3) continuously incorporating new knowledge and concepts into a relational data model. The workflow for managing the content of the system has much in common with the development of the system itself. We examine various aspects of agile software development and discuss whether or how we have been able to use them for data curation as well as software development.

  1. Preparing your Offshore Organization for Agility: Experiences in India

    NASA Astrophysics Data System (ADS)

    Srinivasan, Jayakanth

    Two strategies that have significantly changed the way we conventionally think about managing software development and sustainment are the family of development approaches collectively referred to as agile methods, and the distribution of development efforts on a global scale. When you combine the two strategies, organizations have to address not only the technical challenges that arise from introducing new ways of working, but more importantly have to manage the 'soft' factors that if ignored lead to hard challenges. Using two case studies of distributed agile software development in India we illustrate the areas that organizations need to be aware of when transitioning work to India. The key issues that we emphasize are the need to recruit and retain personnel; the importance of teaching, mentoring and coaching; the need to manage customer expectations; the criticality of well-articulated senior leadership vision and commitment; and the reality of operating in a heterogeneous process environment.

  2. Altered expression of miRNAs and methylation of their promoters are correlated in neuroblastoma

    PubMed Central

    Di Mauro, Stefania; Purrello, Francesco; Magro, Gaetano; Ragusa, Marco; Di Pietro, Cinzia; Romani, Massimo; Purrello, Michele

    2016-01-01

    Neuroblastoma is the most common human extracranial solid tumor during infancy. Involvement of several miRNAs in its pathogenesis has been ascertained. Interestingly, most of their encoding genes reside in hypermethylated genomic regions: thus, their tumor suppressor function is normally disallowed in these tumors. To date, the therapeutic role of the demethylating agent 5′-Aza-2 deoxycytidine (5'-AZA) and its effects on miRNAome modulation in neuroblastoma have not been satisfactorily explored. Starting from a high-throughput expression profiling of 754 miRNAs and based on a proper selection, we focused on miR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p as candidate miRNAs for our analysis. They resulted downregulated in four neuroblastoma cell lines with respect to normal adrenal gland. MiRNAs 29a-3p and 34b-3p also resulted downregulated in vivo in a murine neuroblastoma progression model. Unlike the amount of methylation of their encoding gene promoters, all these miRNAs were significantly overexpressed following treatment with 5′-AZA. Transfection with candidate miRNAs mimics significantly decreased neuroblastoma cells proliferation rate. A lower expression of miR-181c was significantly associated to a worse overall survival in a public dataset of 498 neuroblastoma samples (http://r2.amc.nl). Our data strongly suggest that CDK6, DNMT3A, DNMT3B are targets of miR-29a-3p, while CCNE2 and E2F3 are targets of miR-34b-3p. Based on all these data, we propose that miR-29a-3p, miR-34b-3p, miR-181c-5p and miR-517a-3p are disallowed tumor suppressor genes in neuroblastoma and suggest them as new therapeutic targets in neuroblastoma. PMID:27829219

  3. DoD Acquisitions Reform: Embracing and Implementing Agile

    DTIC Science & Technology

    2015-12-01

    austerity, the DoD must focus on Agile implementation in three main areas: training, business process re-engineering and contracting guidance.   It ...specific recommendations and bound the topic of research, the focus of this paper is on information technology ( IT ) acquisitions specifically, which...The B-52 lived and died by the quality of its sheet metal. Today, our aircraft will live or die by the quality of our software” (Hagan, Hurt

  4. Sprint, agility, strength and endurance capacity in wheelchair basketball players

    PubMed Central

    Granados, C; Otero, M; Badiola, A; Olasagasti, J; Bidaurrazaga-Letona, I; Iturricastillo, A; Gil, SM

    2014-01-01

    The aims of the present study were, firstly, to determine the reliability and reproducibility of an agility T-test and Yo-Yo 10 m recovery test; and secondly, to analyse the physical characteristics measured by sprint, agility, strength and endurance field tests in wheelchair basketball (WB) players. 16 WB players (33.06 ± 7.36 years, 71.89 ± 21.71 kg and sitting body height 86.07 ± 6.82 cm) belonging to the national WB league participated in this study. Wheelchair sprint (5 and 20 m without ball, and 5 and 20 m with ball) agility (T-test and pick-up test) strength (handgrip and maximal pass) and endurance (Yo-Yo 10 m recovery test) were performed. T-test and Yo-Yo 10 m recovery test showed good reproducibility values (intraclass correlation coefficient, ICC = 0.74-0.94). The WB players’ results in 5 and 20 m sprints without a ball were 1.87 ± 0.21 s and 5.70 ± 0.43 s and with a ball 2.10 ± 0.30 s and 6.59 ± 0.61 s, being better than those reported in the literature. Regarding the pick-up test results (16.05 ± 0.52 s) and maximal pass (8.39 ± 1.77 m), players showed worse values than those obtained in elite players. The main contribution of the present study is the characterization of the physical performance profile of WB players using a field test battery. Furthermore, we demonstrated that the agility T-test and the aerobic Yo-Yo 10 m recovery test are reliable; consequently they may be appropriate instruments for measuring physical fitness in WB. PMID:25729153

  5. Achieving Agility and Stability in Large-Scale Software Development

    DTIC Science & Technology

    2013-01-16

    question Which software development process are you currently using? 1. Agile software development (e.g., using Scrum , XP practices, test-driven... Scrum teams, product development teams, component teams, feature teams) spend almost all of their time fixing defects, and new capability...architectural runway provides the degree of architectural stability to support the next n iterations of development. In a Scrum project environment

  6. Achieving Agility and Stability in Large-Scale Software Development

    DTIC Science & Technology

    2013-01-16

    question Which software development process are you currently using? 1. Agile software development (e.g., using Scrum , XP practices, test-driven... Scrum teams, product development teams, component teams, feature teams) spend almost all of their time fixing defects, and new capability...architectural runway provides the degree of architectural stability to support the next n iterations of development. In a Scrum project environment, the

  7. Integrating Agile Combat Support within Title 10 Wargames

    DTIC Science & Technology

    2015-03-26

    incorporate logistics into Air Force Title 10 wargames. More specifically, we capture Air Force Materiel Command’s (AFMC) Agile Combat Support (ACS...within an unclassified general wargame scenario. Logistics has been omitted from wargames for a multitude of reasons throughout the years. We...develop a logistics simulation model of a simplified wargame scenario designed to be run within the Logistics Composite Model (LCOM) Analysis Toolkit

  8. In Pursuit of Agile Acquisition: Are We There Yet?

    DTIC Science & Technology

    2013-03-01

    bureaucracy in the methodology, and avoid promoting activities that would further expand regulatory guidance and oversight to improve agility. Once an...through an integrated digital system called Blue Force Tracker . Instead of the lack of situational awareness, units now use streaming video to help...to trace forensics collected at other crime scenes or events and trace the data back to specific individuals thus identifying dangerous insurgents

  9. ROADM architectures and technologies for agile optical networks

    NASA Astrophysics Data System (ADS)

    Eldada, Louay A.

    2007-02-01

    We review the different optoelectronic component and module technologies that have been developed for use in ROADM subsystems, and describe their principles of operation, designs, features, advantages, and challenges. We also describe the various needs for reconfigurable optical add/drop switching in agile optical networks. For each network need, we present the different ROADM subsystem architecture options with their pros and cons, and describe the optoelectronic technologies supporting each architecture.

  10. Laser agile illumination for object tracking and classification - Feasibility study

    NASA Technical Reports Server (NTRS)

    Scholl, Marija S.; Vanzyl, Jakob J.; Meinel, Aden B.; Meinel, Marjorie P.; Scholl, James W.

    1988-01-01

    The 'agile illumination' concept for discrimination between ICBM warheads and decoys involves a two-aperture illumination with coherent light, diffraction of light by propagation, and a resulting interference pattern on the object surface. A scanning two-beam interference pattern illuminates one object at a time; depending on the shape, momentum, spinning, and tumbling characteristics of the interrogated object, different temporal signals will be obtained for different classes of objects.

  11. Force Projection, Strategic Agility and the Big Meltdown

    DTIC Science & Technology

    2001-05-18

    UNLIMITED Number of Pages 29 ii Abstract of FORCE PROJECTION, STRATEGIC AGILITY AND THE BIG MELTDOWN Due to global warming , the polar icepack which...INTRODUCTION The polar icecap which covers the Arctic Ocean is melting. It is a well-known, scientific fact. Global warming is the generally...operational factors and functions, as applicable. 3 CHAPTER II BACKGROUND Global Warming and the Arctic During this and the last century, researchers have

  12. Biological Inspiration for Agile Autonomous Air Vehicles

    DTIC Science & Technology

    2007-11-01

    vehicles in confined airspace will quickly exceed the abilities of a remote human operator, substantial autonomy is essential. The political, ethical ...and Kirschner, 1997 provide an in-depth but accessible discussion on the interplay of biochemistry, genetics and embryology in animal evolution

  13. Clustering-based urbanisation to improve enterprise information systems agility

    NASA Astrophysics Data System (ADS)

    Imache, Rabah; Izza, Said; Ahmed-Nacer, Mohamed

    2015-11-01

    Enterprises are daily facing pressures to demonstrate their ability to adapt quickly to the unpredictable changes of their dynamic in terms of technology, social, legislative, competitiveness and globalisation. Thus, to ensure its place in this hard context, enterprise must always be agile and must ensure its sustainability by a continuous improvement of its information system (IS). Therefore, the agility of enterprise information systems (EISs) can be considered today as a primary objective of any enterprise. One way of achieving this objective is by the urbanisation of the EIS in the context of continuous improvement to make it a real asset servicing enterprise strategy. This paper investigates the benefits of EISs urbanisation based on clustering techniques as a driver for agility production and/or improvement to help managers and IT management departments to improve continuously the performance of the enterprise and make appropriate decisions in the scope of the enterprise objectives and strategy. This approach is applied to the urbanisation of a tour operator EIS.

  14. Agile Data Curation at a State Geological Survey

    NASA Astrophysics Data System (ADS)

    Hills, D. J.

    2015-12-01

    State agencies, including geological surveys, are often the gatekeepers for myriad data products essential for scientific research and economic development. For example, the Geological Survey of Alabama (GSA) is mandated to explore for, characterize, and report Alabama's mineral, energy, water, and biological resources in support of economic development, conservation, management, and public policy for the betterment of Alabama's citizens, communities, and businesses. As part of that mandate, the GSA has increasingly been called upon to make our data more accessible to stakeholders. Even as demand for greater data accessibility grows, budgets for such efforts are often small, meaning that agencies must do more for less. Agile software development has yielded efficient, effective products, most often at lower cost and in shorter time. Taking guidance from the agile software development model, the GSA is working towards more agile data management and curation. To date, the GSA's work has been focused primarily on data rescue. By using workflows that maximize clear communication while encouraging simplicity (e.g., maximizing the amount of work not done or that can be automated), the GSA is bringing decades of dark data into the light. Regular checks by the data rescuer with the data provider (or their proxy) provides quality control without adding an overt burden on either party. Moving forward, these workflows will also allow for more efficient and effective data management.

  15. Observing peculiar γ-ray pulsars with AGILE

    NASA Astrophysics Data System (ADS)

    Pilia, M.; Pellizzoni, A.

    2011-08-01

    The AGILE γ-ray satellite provides large sky exposure levels (>=109 cm2 s per year on the Galactic Plane) with sensitivity peaking at E ~100 MeV where the bulk of pulsar energy output is typically released. Its ~1 μs absolute time tagging capability makes it perfectly suited for the study of γ-ray pulsars. AGILE collected a large number of γ-ray photons from EGRET pulsars (>=40,000 pulsed counts for Vela) in two years of observations unveiling new interesting features at sub-millisecond level in the pulsars' high-energy light-curves, γ-ray emission from pulsar glitches and Pulsar Wind Nebulae. AGILE detected about 20 nearby and energetic pulsars with good confidence through timing and/or spatial analysis. Among the newcomers we find pulsars with very high rotational energy losses, such as the remarkable PSR B1509-58 with a magnetic field in excess of 1013 Gauss, and PSR J2229+6114 providing a reliable identification for the previously unidentified EGRET source 3EG2227+6122. Moreover, the powerful millisecond pulsar B1821-24, in the globular cluster M28, is detected during a fraction of the observations.

  16. Integrating a distributed, agile, virtual enterprise in the TEAM program

    NASA Astrophysics Data System (ADS)

    Cobb, C. K.; Gray, W. Harvey; Hewgley, Robert E.; Klages, Edward J.; Neal, Richard E.

    1997-01-01

    The technologies enabling agile manufacturing (TEAM) program enhances industrial capability by advancing and deploying manufacturing technologies that promote agility. TEAM has developed a product realization process that features the integration of product design and manufacturing groups. TEAM uses the tools it collects, develops, and integrates in support of the product realization process to demonstrate and deploy agile manufacturing capabilities for three high- priority processes identified by industry: material removal, forming, and electromechanical assembly. In order to provide a proof-of-principle, the material removal process has been addressed first and has been successfully demonstrate din an 'interconnected' mode. An internet-accessible intersite file manager (IFM) application has been deployed to allow geographically distributed TEAM participants to share and distribute information as the product realization process is executed. An automated inspection planning application has been demonstrated, importing a solid model form the IFM, generating an inspection plan and a part program to be used in the inspection process, and then distributing the part program to the inspection site via the IFM. TEAM seeks to demonstrate the material removal process in an integrated mode in June 1997 complete with an object-oriented framework and infrastructure. The current status and future plans for this project are presented here.

  17. The reliability of a functional agility test for water polo.

    PubMed

    Tucher, Guilherme; de Souza Castro, Flávio Antônio; Garrido, Nuno Domingos; Martins da Silva, António José Rocha

    2014-06-28

    Few functional agility tests for water polo take into consideration its specific characteristics. The preliminary objective of this study was to evaluate the reliability of an agility test for water polo players. Fifteen players (16.3 ± 1.8 years old) with a minimum of two years of competitive experience were evaluated. A Functional Test for Agility Performance (FTAP) was designed to represent the context of this sport. Several trials were performed to familiarize the athlete with the movement. Two experienced coaches measured three repetitions of the FTAP. Descriptive statistics, repeated measures analysis of variance (ANOVA), 95% limit of agreement (LOA), intraclass correlation coefficient (ICC) and standard error of measurements (SEM) were used for data analysis. It was considered that certain criteria of reliability measures were met. There was no significant difference between the repetitions, which may be explained by an effect of the evaluator, the ability of the players or fatigue (p > 0.05). The ICC average from evaluators was high (0.88). The SEM varied between 0.13 s and 0.49 s. The CV average considering each individual was near 6-7%. These values depended on the condition of measurement. As the FTAP contains some characteristics that create a degree of unpredictability, the same athlete may reach different performance results, increasing variability. An adjustment in the sample, familiarization and careful selection of subjects help to improve this situation and enhance the reliability of the indicators.

  18. Agile Science Operations: A New Approach for Primitive Exploration Bodies

    NASA Technical Reports Server (NTRS)

    Chien, Steve A.; Thompson, David R.; Castillo-Rogez, Julie C.; Doyle, Richard; Estlin, Tara; Mclaren, David

    2012-01-01

    Primitive body exploration missions such as potential Comet Surface Sample Return or Trojan Tour and Rendezvous would challenge traditional operations practices. Earth-based observations would provide only basic understanding before arrival and many science goals would be defined during the initial rendezvous. It could be necessary to revise trajectories and observation plans to quickly characterize the target for safe, effective observations. Detection of outgassing activity and monitoring of comet surface activity are even more time constrained, with events occurring faster than round-trip light time. "Agile science operations" address these challenges with contingency plans that recognize the intrinsic uncertainty in the operating environment and science objectives. Planning for multiple alternatives can significantly improve the time required to repair and validate spacecraft command sequences. When appropriate, time-critical decisions can be automated and shifted to the spacecraft for immediate access to instrument data. Mirrored planning systems on both sides of the light-time gap permit transfer of authority back and forth as needed. We survey relevant science objectives, identifying time bottlenecks and the techniques that could be used to speed missions' reaction to new science data. Finally, we discuss the results of a trade study simulating agile observations during flyby and comet rendezvous scenarios. These experiments quantify instrument coverage of key surface features as a function of planning turnaround time. Careful application of agile operations techniques can play a significant role in realizing the Decadal Survey plan for primitive body exploration

  19. SAR imagery using chaotic carrier frequency agility pulses

    NASA Astrophysics Data System (ADS)

    Xu, Xiaojian; Feng, Xiangzhi

    2011-06-01

    Synthetic aperture radar (SAR) systems are getting more and more applications in both civilian and military remote sensing missions. With the increasing deployment of electronic countermeasures (ECM) on modern battlefields, SAR encounters more and more interference jamming signals. The ECM jamming signals cause the SAR system to receive and process erroneous information which results in severe degradations in the output SAR images and/or formation of phony images of nonexistent targets. As a consequence, development of the electronic counter-countermeasures (ECCM) capability becomes one of the key problems in SAR system design. This paper develops radar signaling strategies and algorithms that enhance the ability of synthetic aperture radar to image targets under conditions of electronic jamming. The concept of SAR using chaotic carrier frequency agility pulses (CCFAP-SAR) is first proposed. Then the imaging procedure for CCFAP-SAR is discussed in detail. The ECCM performance of CCFAP-SAR for both depressive noise jamming and deceptive repeat jamming is analyzed. The impact of the carrier frequency agility range on the image quality of CCFAP-SAR is also studied. Simulation results demonstrate that, with adequate agility range of the carrier frequency, the proposed CCFAP-SAR performs as well as conventional radar with linear frequency modulation (LFM) waveform in image quality and slightly better in anti-noise depressive jamming; while performs very well in anti-deception jamming which cannot be rejected by LFM-SAR.

  20. Regulation of Bone Formation During Disuse by miRNA

    NASA Technical Reports Server (NTRS)

    Thomas, Nicholas; Choi, Catherine Y.; Alwood, Joshua S.

    2016-01-01

    Astronauts lose bone structure during long-duration spaceflight. These changes are due, in part, to insufficient bone formation by the osteoblast cells. Little is known about the role that small (approximately 22 nucleotide), non-coding micro-RNAs (miRNAs) play in the osteoblast response to microgravity. We hypothesize that osteoblast-lineage cells alter their miRNA status during microgravity exposure, contributing to impaired bone formation during weightlessness. To simulate weightlessness, female mice (C57BL/6, Charles River, 10 weeks of age, n = 6) were hindlimb unloaded for 12 days. Age-matched and normally ambulating mice served as controls (n=6). To assess the expression of miRNAs in skeletal tissue, the right and left tibia of the mice were collected ex vivo and cleaned of soft-tissue and marrow. Total RNA was collected from tibial bone and relative abundance was measured for miRNAs of interest using quantitative real time PCR array looking at 372 unique and well-characterized mature miRNAs using the delta-delta Ct method. Transcripts of interest were normalized to an average of 6 reference RNAs. Preliminary results show that hindlimb unloading decreased the expression of 14 miRNAs to less than 1.4-2.9X control levels and increased the expression of 5 miRNAs relative to the control mice greater than 1-2-1.5X (p less than 0.05, respectively). Using the miRSystem we assessed overlapping target genes predicted to be regulated by multiple members of the 19 differentially expressed miRNAs as well as in silico predicted targets of our individual miRNAs. Our miRSystem results indicated that a number of our differentially expressed miRNAs were regulators of genes related to the Wnt-Beta Catenin pathway-a known regulator of bone health-and, interestingly, the estrogen-mediated cell-cycle regulation pathway, which may indicate that simulated weightlessness induced systemic hormonal changes that contributed to bone loss. We plan to follow up these findings by measuring

  1. Airway Epithelial miRNA Expression Is Altered in Asthma

    PubMed Central

    Solberg, Owen D.; Ostrin, Edwin J.; Love, Michael I.; Peng, Jeffrey C.; Bhakta, Nirav R.; Nguyen, Christine; Solon, Margaret; Nguyen, Cindy; Barczak, Andrea J.; Zlock, Lorna T.; Blagev, Denitza P.; Finkbeiner, Walter E.; Ansel, K. Mark; Arron, Joseph R.; Erle, David J.

    2012-01-01

    Rationale: Changes in airway epithelial cell differentiation, driven in part by IL-13, are important in asthma. Micro-RNAs (miRNAs) regulate cell differentiation in many systems and could contribute to epithelial abnormalities in asthma. Objectives: To determine whether airway epithelial miRNA expression is altered in asthma and identify IL-13–regulated miRNAs. Methods: We used miRNA microarrays to analyze bronchial epithelial brushings from 16 steroid-naive subjects with asthma before and after inhaled corticosteroids, 19 steroid-using subjects with asthma, and 12 healthy control subjects, and the effects of IL-13 and corticosteroids on cultured bronchial epithelial cells. We used quantitative polymerase chain reaction to confirm selected microarray results. Measurements and Main Results: Most (12 of 16) steroid-naive subjects with asthma had a markedly abnormal pattern of bronchial epithelial miRNA expression by microarray analysis. Compared with control subjects, 217 miRNAs were differentially expressed in steroid-naive subjects with asthma and 200 in steroid-using subjects with asthma (false discovery rate < 0.05). Treatment with inhaled corticosteroids had modest effects on miRNA expression in steroid-naive asthma, inducing a statistically significant (false discovery rate < 0.05) change for only nine miRNAs. qPCR analysis confirmed differential expression of 22 miRNAs that were highly differentially expressed by microarrays. IL-13 stimulation recapitulated changes in many differentially expressed miRNAs, including four members of the miR-34/449 family, and these changes in miR-34/449 family members were resistant to corticosteroids. Conclusions: Dramatic alterations of airway epithelial cell miRNA levels are a common feature of asthma. These alterations are only modestly corrected by inhaled corticosteroids. IL-13 effects may account for some of these alterations, including repression of miR-34/449 family members that have established roles in airway

  2. miRNA in Macrophage Development and Function

    PubMed Central

    2016-01-01

    Abstract Significance: MicroRNAs (miRNAs) control cellular gene expression via primarily binding to 3′ or 5′ untranslated region of the target transcript leading to translational repression or mRNA degradation. In most cases, miRNAs have been observed to fine-tune the cellular responses and, therefore, act as a rheostat rather than an on/off switch. Transcription factor PU.1 is a master switch that controls monocyte/macrophage development from hematopoietic stem cells. Recent Advances: PU.1 induces a specific set of miRNAs while suppressing the miR17-92 cluster to regulate monocyte/macrophage development. In addition to development, miRNAs tightly control the macrophage polarization continuum from proinflammatory M1 or proreparative M2 by regulating expression of key transcription factors involved in the process of polarization. Critical Issues: miRNAs are intricately involved with fine-tuning fundamental macrophage functions such as phagocytosis, efferocytosis, inflammation, tissue repair, and tumor promotion. Macrophages are secretory cells that participate in intercellular communication by releasing regulatory molecules and microvesicles (MVs). MVs are bilayered lipid membranes packaging a hydrophilic cargo, including proteins and nucleic acids. Macrophage-derived MVs carry functionally active miRNAs that suppress gene expression in target cells via post-transcriptional gene silencing, thus regulating cell function. In summary, miRNAs fine-tune several major facets of macrophage development and function. Such fine-tuning is critical in preventing exaggerated macrophage response to endogenous or exogenous stimuli. Future Directions: A critical role of miRNAs in the regulation of innate immune response and macrophage biology, including development, differentiation, and activation, has emerged. A clear understanding of such regulation on macrophage function remains to be elucidated. Antioxid. Redox Signal. 25, 795–804. PMID:27353423

  3. MicroRNA (miRNA) cloning analysis reveals sex differences in miRNA expression profiles between adult mouse testis and ovary.

    PubMed

    Mishima, Takuya; Takizawa, Takami; Luo, Shan-Shun; Ishibashi, Osamu; Kawahigashi, Yutaka; Mizuguchi, Yoshiaki; Ishikawa, Tomoko; Mori, Miki; Kanda, Tomohiro; Goto, Tadashi; Takizawa, Toshihiro

    2008-12-01

    MicroRNAs (miRNAs) are endogenous non-coding small RNAs that can regulate the expression of complementary mRNA targets. Identifying tissue-specific miRNAs is the first step toward understanding the biological functions of miRNAs, which include the regulation of tissue differentiation and the maintenance of tissue identity. In this study, we performed small RNA library sequencing in adult mouse testis and ovary to reveal their characteristic organ- and gender-specific profiles and to elucidate the characteristics of the miRNAs expressed in the reproductive system. We obtained 10,852 and 11 744 small RNA clones from mouse testis and ovary respectively (greater than 10,000 clones per organ), which included 6630 (159 genes) and 10,192 (154 genes) known miRNAs. A high level of efficiency of miRNA library sequencing was achieved: 61% (6630 miRNA clones/10,852 small RNA clones) and 87% (10,192/11,744) for adult mouse testis and ovary respectively. We obtained characteristic miRNA signatures in testis and ovary; 55 miRNAs were detected highly, exclusively, or predominantly in adult mouse testis and ovary, and discovered two novel miRNAs. Male-biased expression of miRNAs occurred on the X-chromosome. Our data provide important information on sex differences in miRNA expression that should facilitate studies of the reproductive organ-specific roles of miRNAs.

  4. A Combination of Human Embryonic Stem Cell-Derived Pancreatic Endoderm Transplant with LDHA-Repressing miRNA Can Attenuate High-Fat Diet Induced Type II Diabetes in Mice

    PubMed Central

    Chen, Yunya; Wang, Xiujie; Shao, Xinyu

    2015-01-01

    Type II diabetes mellitus (T2D) is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. The deficit and dysfunction of insulin secreting β-cell are signature symptom for T2D. Additionally, in pancreatic β-cell, a small group of genes which are abundantly expressed in most other tissues are highly selectively repressed. Lactate dehydrogenase A (LDHA) is one of such genes. Upregulation of LDHA is found in both human T2D and rodent T2D models. In this study, we identified a LDHA-suppressing microRNA (hsa-miR-590-3p) and used it together with human embryonic stem cell (hESC) derived pancreatic endoderm (PE) transplantation into a high-fat diet induced T2D mouse model. The procedure significantly improved glucose metabolism and other symptoms of T2D. Our findings support the potential T2D treatment using the combination of microRNA and hESC-differentiated PE cells. PMID:26770982

  5. Towards a Framework for Using Agile Approaches in Global Software Development

    NASA Astrophysics Data System (ADS)

    Hossain, Emam; Ali Babar, Muhammad; Verner, June

    As agile methods and Global Software Development (GSD) are become increasingly popular, GSD project managers have been exploring the viability of using agile approaches in their development environments. Despite the expected benefits of using an agile approach with a GSD project, the overall combining mechanisms of the two approaches are not clearly understood. To address this challenge, we propose a conceptual framework, based on the research literature. This framework is expected to aid a project manager in deciding what agile strategies are effective for a particular GSD project, taking into account project context. We use an industry-based case study to explore the components of our conceptual framework. Our case study is planned and conducted according to specific published case study guidelines. We identify the agile practices and agile supporting practices used by a GSD project manager in our case study and conclude with future research directions.

  6. Final Report of the NASA Office of Safety and Mission Assurance Agile Benchmarking Team

    NASA Technical Reports Server (NTRS)

    Wetherholt, Martha

    2016-01-01

    To ensure that the NASA Safety and Mission Assurance (SMA) community remains in a position to perform reliable Software Assurance (SA) on NASAs critical software (SW) systems with the software industry rapidly transitioning from waterfall to Agile processes, Terry Wilcutt, Chief, Safety and Mission Assurance, Office of Safety and Mission Assurance (OSMA) established the Agile Benchmarking Team (ABT). The Team's tasks were: 1. Research background literature on current Agile processes, 2. Perform benchmark activities with other organizations that are involved in software Agile processes to determine best practices, 3. Collect information on Agile-developed systems to enable improvements to the current NASA standards and processes to enhance their ability to perform reliable software assurance on NASA Agile-developed systems, 4. Suggest additional guidance and recommendations for updates to those standards and processes, as needed. The ABT's findings and recommendations for software management, engineering and software assurance are addressed herein.

  7. Cell-free Circulating miRNA Biomarkers in Cancer

    PubMed Central

    Mo, Meng-Hsuan; Chen, Liang; Fu, Yebo; Wang, Wendy; Fu, Sidney W.

    2012-01-01

    Considerable attention and an enormous amount of resources have been dedicated to cancer biomarker discovery and validation. However, there are still a limited number of useful biomarkers available for clinical use. An ideal biomarker should be easily assayed with minimally invasive medical procedures but possess high sensitivity and specificity. Commonly used circulating biomarkers are proteins in serum, most of which require labor-intensive analysis hindered by low sensitivity in early tumor detection. Since the deregulation of microRNA (miRNA) is associated with cancer development and progression, profiling of circulating miRNAs has been used in a number of studies to identify novel minimally invasive miRNA biomarkers. In this review, we discuss the origin of the circulating cell-free miRNAs and their carriers in blood. We summarize the clinical use and function of potentially promising miRNA biomarkers in a variety of different cancers, along with their downstream target genes in tumor initiation and development. Additionally, we analyze some technical challenges in applying miRNA biomarkers to clinical practice. PMID:23074383

  8. miRNA regulation of nutrient homeostasis in plants

    PubMed Central

    Paul, Soumitra; Datta, Swapan K.; Datta, Karabi

    2015-01-01

    Small RNAs including micro RNAs (miRNA) play an indispensable role in cell signaling mechanisms. Generally, miRNAs that are 20–24 nucleotides long bind to specific complementary transcripts, attenuating gene expression at the post-transcriptional level or via translational inhibition. In plants, miRNAs have emerged as the principal regulator of various stress responses, including low nutrient availability. It has been reported that miRNAs are vital for maintaining nutrient homeostasis in plants by regulating the expression of transporters that are involved in nutrient uptake and mobilization. The present review highlights the role of various miRNAs in several macro- or micronutrient deficiencies in plants. Understanding the regulation of different transporters by miRNAs will aid in elucidating the underlying molecular signal transduction mechanisms during nutritional stress. Recent findings regarding nutrient related-miRNAs and their gene regulation machinery may delineate a novel platform for improving the nutritional status of cereal grains or crop biofortification programs in the future. PMID:25914709

  9. miRNA profiling in vitreous humor, vitreal exosomes and serum from uveal melanoma patients: Pathological and diagnostic implications

    PubMed Central

    Ragusa, Marco; Barbagallo, Cristina; Statello, Luisa; Caltabiano, Rosario; Russo, Andrea; Puzzo, Lidia; Avitabile, Teresio; Longo, Antonio; Toro, Mario D; Barbagallo, Davide; Valadi, Hadi; Di Pietro, Cinzia; Purrello, Michele; Reibaldi, Michele

    2015-01-01

    Uveal melanoma (UM) represents approximately 5–6% of all melanoma diagnoses and up to 50% of patients succumb to their disease. Although several methods are available, accurate diagnosis is not always easily feasible because of potential accidents (e.g., intraocular hemorrhage). Based on the assumption that the profile of circulating miRNAs is often altered in human cancers, we verified whether UM patients showed different vitreous humor (VH) or serum miRNA profiles with respect to healthy controls. By using TaqMan Low Density Arrays, we analyzed 754 miRNAs from VH, vitreal exosomes, and serum of 6 UM patients and 6 healthy donors: our data demonstrated that the UM VH profile was unique and only partially overlapping with that from serum of the same patients. Whereas, 90% of miRNAs were shared between VH and vitreal exosomes, and their alterations in UM were statistically overlapped with those of VH and vitreal exosomes, suggesting that VH alterations could result from exosomal dysregulation. We report 32 miRNAs differentially expressed in UM patients in at least 2 different types of samples analyzed. We validated these data on an independent cohort of 12 UM patients. Most alterations were common to VH and vitreal exosomes (e.g., upregulation of miR-21,-34 a,-146a). Interestingly, miR-146a was upregulated in the serum of UM patients, as well as in serum exosomes. Upregulation of miR-21 and miR-146a was also detected in formalin-fixed, paraffin-embedded UM, suggesting that VH or serum alterations in UM could be the consequence of disregulation arising from tumoral cells. Our findings suggest the possibility to detect in VH and serum of UM patients “diagnostic” miRNAs released by the affected eye: based on this, miR-146a could be considered a potential circulating marker of UM. PMID:25951497

  10. Mining of public sequencing databases supports a non-dietary origin for putative foreign miRNAs: underestimated effects of contamination in NGS

    PubMed Central

    Tosar, Juan Pablo; Rovira, Carlos; Naya, Hugo; Cayota, Alfonso

    2014-01-01

    The report that exogenous plant miRNAs are able to cross the mammalian gastrointestinal tract and exert gene-regulation mechanism in mammalian tissues has yielded a lot of controversy, both in the public press and the scientific literature. Despite the initial enthusiasm, reproducibility of these results was recently questioned by several authors. To analyze the causes of this unease, we searched for diet-derived miRNAs in deep-sequencing libraries performed by ourselves and others. We found variable amounts of plant miRNAs in publicly available small RNA-seq data sets of human tissues. In human spermatozoa, exogenous RNAs reached extreme, biologically meaningless levels. On the contrary, plant miRNAs were not detected in our sequencing of human sperm cells, which was performed in the absence of any known sources of plant contamination. We designed an experiment to show that cross-contamination during library preparation is a source of exogenous RNAs. These contamination-derived exogenous sequences even resisted oxidation with sodium periodate. To test the assumption that diet-derived miRNAs were actually contamination-derived, we sought in the literature for previous sequencing reports performed by the same group which reported the initial finding. We analyzed the spectra of plant miRNAs in a small RNA sequencing study performed in amphioxus by this group in 2009 and we found a very strong correlation with the plant miRNAs which they later reported in human sera. Even though contamination with exogenous sequences may be easy to detect, cross-contamination between samples from the same organism can go completely unnoticed, possibly affecting conclusions derived from NGS transcriptomics. PMID:24729469

  11. High-Speed Time-Series CCD Photometry with Agile

    NASA Astrophysics Data System (ADS)

    Mukadam, Anjum S.; Owen, R.; Mannery, E.; MacDonald, N.; Williams, B.; Stauffer, F.; Miller, C.

    2011-12-01

    We have assembled a high-speed time-series CCD photometer named Agile for the 3.5 m telescope at Apache Point Observatory, based on the design of a photometer called Argos at McDonald Observatory. Instead of a mechanical shutter, we use the frame-transfer operation of the CCD to end an exposure and initiate the subsequent new exposure. The frame-transfer operation is triggered by the negative edge of a GPS pulse; the instrument timing is controlled directly by hardware, without any software intervention or delays. This is the central pillar in the design of Argos that we have also used in Agile; this feature makes the accuracy of instrument timing better than a millisecond. Agile is based on a Princeton Instruments Acton VersArray camera with a frame-transfer CCD, which has 1K × 1K active pixels, each of size . Using a focal reducer at the Nasmyth focus of the 3.5 m telescope at Apache Point Observatory, we yield a field of view of 2.2 × 2.2 arcmin2 with an unbinned plate scale of 0.13″ pixel-1. The CCD is back-illuminated and thinned for improved blue sensitivity and provides a quantum efficiency ≥80% in the wavelength range of 4500–7500 Å. The unbinned full-frame readout time can be as fast as 1.1 s this is achieved using a low-noise amplifier operating at 1 MHz with an average read noise of the order of rms. At the slow read rate of 100 kHz to be used for exposure times longer than a few seconds, we determine an average read noise of the order of rms. Agile is optimized to observe variability at short timescales from one-third of a second to several hundred seconds. The variable astronomical sources routinely observed with Agile include pulsating white dwarfs, cataclysmic variables, flare stars, planetary transits, and planetary satellite occultations.

  12. Identification of miRNAs Potentially Involved in Bronchiolitis Obliterans Syndrome: A Computational Study

    PubMed Central

    Politano, Gianfranco; Inghilleri, Simona; Morbini, Patrizia; Calabrese, Fiorella; Benso, Alfredo; Savino, Alessandro; Cova, Emanuela; Zampieri, Davide; Meloni, Federica

    2016-01-01

    The pathogenesis of Bronchiolitis Obliterans Syndrome (BOS), the main clinical phenotype of chronic lung allograft dysfunction, is poorly understood. Recent studies suggest that epigenetic regulation of microRNAs might play a role in its development. In this paper we present the application of a complex computational pipeline to perform enrichment analysis of miRNAs in pathways applied to the study of BOS. The analysis considered the full set of miRNAs annotated in miRBase (version 21), and applied a sequence of filtering approaches and statistical analyses to reduce this set and to score the candidate miRNAs according to their potential involvement in BOS development. Dysregulation of two of the selected candidate miRNAs–miR-34a and miR-21 –was clearly shown in in-situ hybridization (ISH) on five explanted human BOS lungs and on a rat model of acute and chronic lung rejection, thus definitely identifying miR-34a and miR-21 as pathogenic factors in BOS and confirming the effectiveness of the computational pipeline. PMID:27564214

  13. Phosphorylation of DGCR8 increases its intracellular stability and induces a progrowth miRNA profile.

    PubMed

    Herbert, Kristina M; Pimienta, Genaro; DeGregorio, Suzanne J; Alexandrov, Andrei; Steitz, Joan A

    2013-11-27

    During miRNA biogenesis, the microprocessor complex (MC), which is composed minimally of Drosha, an RNase III enzyme, and DGCR8, a double-stranded RNA-binding protein, cleaves the primary miRNA (pri-miRNA) in order to release the pre-miRNA stem-loop structure. Using phosphoproteomics, we mapped 23 phosphorylation sites on full-length human DGCR8 expressed in insect or mammalian cells. DGCR8 can be phosphorylated by mitogenic ERK/MAPK, indicating that DGCR8 phosphorylation may respond to and integrate extracellular cues. The expression of phosphomimetic DGCR8 or inhibition of phosphatases increased the cellular levels of DGCR8 and Drosha proteins. Increased levels of phosphomimetic DGCR8 were not due to higher mRNA levels, altered DGCR8 localization, or DGCR8's ability to self-associate, but rather to an increase in protein stability. MCs incorporating phosphomutant or phosphomimetic DGCR8 were not altered in specific processing activity. However, HeLa cells expressing phosphomimetic DGCR8 exhibited a progrowth miRNA expression profile and increased proliferation and scratch closure rates relative to cells expressing phosphomutant DGCR8.

  14. Phosphorylation of DGCR8 Increases Its Intracellular Stability and Induces a Progrowth miRNA Profile

    PubMed Central

    Herbert, Kristina M.; Pimienta, Genaro; DeGregorio, Suzanne J.; Alexandrov, Andrei; Steitz, Joan A.

    2014-01-01

    SUMMARY During miRNA biogenesis, the microprocessor complex (MC), which is composed minimally of Drosha, an RNase III enzyme, and DGCR8, a double-stranded RNA-binding protein, cleaves the primary miRNA (pri-miRNA) in order to release the pre-miRNA stem-loop structure. Using phosphoproteomics, we mapped 23 phosphorylation sites on full-length human DGCR8 expressed in insect or mammalian cells. DGCR8 can be phosphorylated by mitogenic ERK/MAPK, indicating that DGCR8 phosphorylation may respond to and integrate extracellular cues. The expression of phosphomimetic DGCR8 or inhibition of phosphatases increased the cellular levels of DGCR8 and Drosha proteins. Increased levels of phosphomimetic DGCR8 were not due to higher mRNA levels, altered DGCR8 localization, or DGCR8’s ability to self-associate, but rather to an increase in protein stability. MCs incorporating phosphomutant or phosphomimetic DGCR8 were not altered in specific processing activity. However, HeLa cells expressing phosphomimetic DGCR8 exhibited a progrowth miRNA expression profile and increased proliferation and scratch closure rates relative to cells expressing phosphomutant DGCR8. PMID:24239349

  15. Defining Transcriptional Regulatory Mechanisms for Primary let-7 miRNAs.

    PubMed

    Gaeta, Xavier; Le, Luat; Lin, Ying; Xie, Yuan; Lowry, William E

    2017-01-01

    The let-7 family of miRNAs have been shown to control developmental timing in organisms from C. elegans to humans; their function in several essential cell processes throughout development is also well conserved. Numerous studies have defined several steps of post-transcriptional regulation of let-7 production; from pri-miRNA through pre-miRNA, to the mature miRNA that targets endogenous mRNAs for degradation or translational inhibition. Less-well defined are modes of transcriptional regulation of the pri-miRNAs for let-7. let-7 pri-miRNAs are expressed in polycistronic fashion, in long transcripts newly annotated based on chromatin-associated RNA-sequencing. Upon differentiation, we found that some let-7 pri-miRNAs are regulated at the transcriptional level, while others appear to be constitutively transcribed. Using the Epigenetic Roadmap database, we further annotated regulatory elements of each polycistron identified putative promoters and enhancers. Probing these regulatory elements for transcription factor binding sites identified factors that regulate transcription of let-7 in both promoter and enhancer regions, and identified novel regulatory mechanisms for this important class of miRNAs.

  16. Defining Transcriptional Regulatory Mechanisms for Primary let-7 miRNAs

    PubMed Central

    Gaeta, Xavier; Le, Luat; Lin, Ying; Xie, Yuan; Lowry, William E.

    2017-01-01

    The let-7 family of miRNAs have been shown to control developmental timing in organisms from C. elegans to humans; their function in several essential cell processes throughout development is also well conserved. Numerous studies have defined several steps of post-transcriptional regulation of let-7 production; from pri-miRNA through pre-miRNA, to the mature miRNA that targets endogenous mRNAs for degradation or translational inhibition. Less-well defined are modes of transcriptional regulation of the pri-miRNAs for let-7. let-7 pri-miRNAs are expressed in polycistronic fashion, in long transcripts newly annotated based on chromatin-associated RNA-sequencing. Upon differentiation, we found that some let-7 pri-miRNAs are regulated at the transcriptional level, while others appear to be constitutively transcribed. Using the Epigenetic Roadmap database, we further annotated regulatory elements of each polycistron identified putative promoters and enhancers. Probing these regulatory elements for transcription factor binding sites identified factors that regulate transcription of let-7 in both promoter and enhancer regions, and identified novel regulatory mechanisms for this important class of miRNAs. PMID:28052101

  17. Role of inflammation and its miRNA based regulation in epilepsy: Implications for therapy.

    PubMed

    Srivastava, Arpna; Dixit, Aparna Banerjee; Banerjee, Jyotirmoy; Tripathi, Manjari; Sarat Chandra, P

    2016-01-15

    There is a need to develop innovative therapeutic strategies to counteract epilepsy, a common disabling neurological disorder. Despite the recent advent of additional antiepileptic drugs and respective surgery, the treatment of epilepsy remains a major challenge. The available therapies are largely based on symptoms, and these approaches do not affect the underlying disease processes and are also associated frequently with severe side effects. This is mainly because of the lack of well-defined targets in epilepsy. The discovery that inflammatory mediators significantly contribute to the onset and recurrence of seizures in experimental seizure models, as well as the presence of inflammatory molecules in human epileptogenic tissue, highlights the possibility of targeting specific inflammation related pathways to control seizures that are otherwise resistant to the available AEDs. Emerging studies suggest that miRNAs have a significant role in regulating inflammatory pathways shown to be involved in epilepsy. These miRNAs can possibly be used as novel therapeutic targets in the treatment of epilepsy as well as serve as diagnostic biomarkers of epileptogenesis. This review highlights the immunological features underlying the pathogenesis of epileptic seizures and the possible miRNA mediated approaches for drug resistant epilepsies that modulate the immune-mediated pathogenesis.

  18. Characterization of Paraquat-Induced miRNA Profiling Response in hNPCs Undergoing Proliferation

    PubMed Central

    Huang, Min; Lou, Dan; Cai, Qian; Chang, Xiuli; Wang, Xinjin; Zhou, Zhijun

    2014-01-01

    Aberration during the development of the central nervous system (CNS) due to environmental factors underlies a variety of adverse developmental outcomes. Paraquat (PQ) is a widely studied neurotoxicant that perturbs the normal structure/function of adult CNS. Yet, the impacts of PQ exposure on the developing CNS remain unclear. miRNAs represent a class of small non-coding RNA molecules involved in the regulation of neural development. Thus in the present study, we analyzed the impacts of PQ on the miRNome of human neural progenitor cells (hNPCs) during proliferation by using the Exiqon miRCURY™ LNA Array. A total of 66 miRNAs were identified as differentially expressed in proliferating hNPCs upon PQ treatment. miRTarBase prediction identified 1465 mRNAs, including several genes (e.g., nestin, sox1, ngn1) previously proved to be associated with the neural proliferation and differentiation, as target genes of PQ-induced differentially expressed miRNAs. The database for annotation, visualization and integrated discovery (DAVID) bioinformatics analysis showed that target genes were enriched in regulation of cell proliferation and differentiation, cell cycle and apoptosis as well as tumor protein 53 (p53), Wnt, Notch and mitogen-activated protein kinases (MAPK) signaling pathways (p < 0.001). These findings were confirmed by real-time RT-PCR. Based on our results we conclude that PQ-induced impacts on the miRNA profiling of hNPCs undergoing proliferation may underlie the developmental neurotoxicity of PQ. PMID:25314302

  19. Nonlinear optical protection against frequency agile lasers

    SciTech Connect

    McDowell, V.P.

    1988-08-04

    An eye-protection or equipment-filter device for protection from laser energy is disclosed. The device may be in the form of a telescope, binoculars, goggles, constructed as part of equipment such as image intensifiers or range designators. Optical elements focus the waist of the beam within a nonlinear frequency-doubling crystal or nonlinear optical element or fiber. The nonlinear elements produce a harmonic outside the visible spectrum in the case of crystals, or absorb the laser energy in the case of nonlinear fibers. Embodiments include protectors for the human eye as well as filters for sensitive machinery such as TV cameras, FLIR systems or other imaging equipment.

  20. Team-based work and work system balance in the context of agile manufacturing.

    PubMed

    Yauch, Charlene A

    2007-01-01

    Manufacturing agility is the ability to prosper in an environment characterized by constant and unpredictable change. The purpose of this paper is to analyze team attributes necessary to facilitate agile manufacturing, and using Balance Theory as a framework, it evaluates the potential positive and negative impacts related to these team attributes that could alter the balance of work system elements and resulting "stress load" experienced by persons working on agile teams. Teams operating within the context of agile manufacturing are characterized as multifunctional, dynamic, cooperative, and virtual. A review of the literature relevant to each of these attributes is provided, as well as suggestions for future research.

  1. The influence of physical and cognitive factors on reactive agility performance in men basketball players.

    PubMed

    Scanlan, Aaron; Humphries, Brendan; Tucker, Patrick S; Dalbo, Vincent

    2014-01-01

    This study explored the influence of physical and cognitive measures on reactive agility performance in basketball players. Twelve men basketball players performed multiple sprint, Change of Direction Speed Test, and Reactive Agility Test trials. Pearson's correlation analyses were used to determine relationships between the predictor variables (stature, mass, body composition, 5-m, 10-m and 20-m sprint times, peak speed, closed-skill agility time, response time and decision-making time) and reactive agility time (response variable). Simple and stepwise regression analyses determined the individual influence of each predictor variable and the best predictor model for reactive agility time. Morphological (r = -0.45 to 0.19), sprint (r = -0.40 to 0.41) and change-of-direction speed measures (r = 0.43) had small to moderate correlations with reactive agility time. Response time (r = 0.76, P = 0.004) and decision-making time (r = 0.58, P = 0.049) had large to very large relationships with reactive agility time. Response time was identified as the sole predictor variable for reactive agility time in the stepwise model (R(2) = 0.58, P = 0.004). In conclusion, cognitive measures had the greatest influence on reactive agility performance in men basketball players. These findings suggest reaction and decision-making drills should be incorporated in basketball training programmes.

  2. Computational identification of miRNAs and their targets in Phaseolus vulgaris.

    PubMed

    Han, J; Xie, H; Kong, M L; Sun, Q P; Li, R Z; Pan, J B

    2014-01-21

    MicroRNAs (miRNAs) are a class of non-coding small RNAs that negatively regulate gene expression at the post-transcriptional level. Although thousands of miRNAs have been identified in plants, limited information is available about miRNAs in Phaseolus vulgaris, despite it being an important food legume worldwide. The high conservation of plant miRNAs enables the identification of new miRNAs in P. vulgaris by homology analysis. Here, 1804 known and unique plant miRNAs from 37 plant species were blast-searched against expressed sequence tag and genomic survey sequence databases to identify novel miRNAs in P. vulgaris. All candidate sequences were screened by a series of miRNA filtering criteria. Finally, we identified 27 conserved miRNAs, belonging to 24 miRNA families. When compared against known miRNAs in P. vulgaris, we found that 24 of the 27 miRNAs were newly discovered. Further, we identified 92 potential target genes with known functions for these novel miRNAs. Most of these target genes were predicted to be involved in plant development, signal transduction, metabolic pathways, disease resistance, and environmental stress response. The identification of the novel miRNAs in P. vulgaris is anticipated to provide baseline information for further research about the biological functions and evolution of miRNAs in P. vulgaris.

  3. Entangling Relation of Micro RNA-let7, miRNA-200 and miRNA-125 with Various Cancers.

    PubMed

    Masood, Nosheen; Yasmin, Azra

    2017-01-09

    Involvement of micro RNAs (miRNA) is currently the focus for cancer studies as they effect the post transcriptional expression of different genes. Let-7 family is among the firstly discovered miRNAs that play important role in cell proliferation and dysregulation leading to cell based diseases including cancer. Another family, miRNA-200 prevents transformation of cell to malignant form and tumor formation by interacting with epidermal mesenchymal transition (EMT). Similarly miRNA-125 controls apoptosis and proliferation by affecting multiple genes involved in transcription, immunological defense, resistance against viral and bacterial infections that ultimately leads to cell proliferation, metastasis and finally cancer. All of these micro RNAs are known to be either upregulated or downregulated in various cancers. Current review is focused to elaborate the role of these three families of micro RNAs on different genes that ultimately cause cancer. In conclusion we can say that the miRNAs discussed here are mostly downregulated in various cancers with some exceptions when upregulation of miRNA-125 may be attributed to cancer formation.

  4. Evaluation of the miRNA profiling and effectiveness of the propolis on B-cell acute lymphoblastic leukemia cell line.

    PubMed

    Yilmaz, Ugur Cem; Bagca, Bakiye Goker; Karaca, Emin; Durmaz, Asude; Durmaz, Burak; Aykut, Ayca; Kayalar, Husniye; Avci, Cigir Biray; Susluer, Sunde Yilmaz; Gunduz, Cumhur; Cogulu, Ozgur

    2016-12-01

    Acute lymphoblastic leukemia (ALL) is one of the most frequent causes of death from cancer. Since the discovery of chemotherapeutic agents, ALL has become a model for improvement of survival. In parallel to this, serious side effects were observed and new natural therapeutic options has been discussed. One of these substances is called propolis which is a resinous substance gathered by honeybees. In the molecular era, miRNAs have been shown to play crucial roles in the development of many clinical conditions. The aim of this study is to evaluate the effect of Aydın propolis on 81 human miRNA activity in CCRF-SB leukemia cell line. Apoptotic effects of propolis on cell lines were also evaluated and apoptosis were found to be induced 1.5 fold in B-cell leukemia cells. The expression of 63 miRNAs (46 miRNAs were downregulated, 19 miRNAs were upregulated) in propolis treated leukemia cells have changed significantly (p<0.05). In conclusion propolis has changed expression of miRNAs which have epigenetic effects on leukemic cells. It is thought that it can be a promising agent for ALL treatment for future studies.

  5. IL-4 Up-Regulates MiR-21 and the MiRNAs Hosted in the CLCN5 Gene in Chronic Lymphocytic Leukemia

    PubMed Central

    Sebastián-Ruiz, Silvia; García-Serna, Azahara-María; Gómez-Espuch, Joaquín; Moraleda, José-María; Minguela, Alfredo; García-Alonso, Ana-María; Parrado, Antonio

    2015-01-01

    Interleukin 4 (IL-4) induces B-cell differentiation and survival of chronic lymphocytic leukemia (CLL) cells. MicroRNAs (miRNAs) regulate mRNA and protein expression, and several miRNAs, deregulated in CLL, might play roles as oncogenes or tumor suppressors. We have studied the miRNA profile of CLL, and its response to IL-4, by oligonucleotide microarrays, resulting in the detection of a set of 129 mature miRNAs consistently expressed in CLL, which included 41 differentially expressed compared to normal B cells (NBC), and 6 significantly underexpressed in ZAP-70 positive patients. IL-4 stimulation brought about up-regulation of the 5p and 3p mature variants of the miR-21 gene, which maps immediately downstream to the VMP1 gene, and of the mature forms generated from the miR-362 (3p and 5p), miR-500a (3p), miR-502 (3p), and miR-532 (3p and 5p) genes, which map within the third intron of the CLCN5 gene. Both genes are in turn regulated by IL-4, suggesting that these miRNAs were regulated by IL-4 as passengers from their carrier genes. Their levels of up-regulation by IL-4 significantly correlated with cytoprotection. MiR-21 has been reported to be leukemogenic, associated to bad prognosis in CLL, and the miRNA more frequently overexpressed in human cancer. Up-regulation by IL-4 of miR-21 and the miRNAs hosted in the CLCN5 locus may contribute to evasion of apoptosis of CLL cells. These findings indicate that the IL-4 pathway and the miRNAs induced by IL-4 are promising targets for the development of novel therapies in CLL. PMID:25909590

  6. Infinity: An In-Silico Tool for Genome-Wide Prediction of Specific DNA Matrices in miRNA Genomic Loci

    PubMed Central

    Garibaldi, Francesca; Manni, Isabella; Filligoi, Giancarlo; Piaggio, Giulia; Gurtner, Aymone

    2016-01-01

    Motivation miRNAs are potent regulators of gene expression and modulate multiple cellular processes in physiology and pathology. Deregulation of miRNAs expression has been found in various cancer types, thus, miRNAs may be potential targets for cancer therapy. However, the mechanisms through which miRNAs are regulated in cancer remain unclear. Therefore, the identification of transcriptional factor–miRNA crosstalk is one of the most update aspects of the study of miRNAs regulation. Results In the present study we describe the development of a fast and user-friendly software, named infinity, able to find the presence of DNA matrices, such as binding sequences for transcriptional factors, on ~65kb (kilobase) of 939 human miRNA genomic sequences, simultaneously. Of note, the power of this software has been validated in vivo by performing chromatin immunoprecipitation assays on a subset of new in silico identified target sequences (CCAAT) for the transcription factor NF-Y on colon cancer deregulated miRNA loci. Moreover, for the first time, we have demonstrated that NF-Y, through its CCAAT binding activity, regulates the expression of miRNA-181a, -181b, -21, -17, -130b, -301b in colon cancer cells. Conclusions The infinity software that we have developed is a powerful tool to underscore new TF/miRNA regulatory networks. Availability and Implementation Infinity was implemented in pure Java using Eclipse framework, and runs on Linux and MS Windows machine, with MySQL database. The software is freely available on the web at https://github.com/bio-devel/infinity. The website is implemented in JavaScript, PHP and HTML with all major browsers supported. PMID:27082112

  7. Forensic miRNA: potential biomarker for body fluids?

    PubMed

    Silva, Sarah S; Lopes, Cátia; Teixeira, A L; Carneiro de Sousa, M J; Medeiros, R

    2015-01-01

    In forensic investigation, body fluids represent an important support to professionals when detected, collected and correctly identified. Through many years, various approaches were used, namely serology-based methodologies however, their lack of sensitivity and specificity became difficult to set aside. In order to sidetrack the problem, miRNA profiling surged with a real potential to be used to identify evidences like urine, blood, menstrual blood, saliva, semen and vaginal secretions. MiRNAs are small RNA structures with 20-25 nt whose proprieties makes them less prone to degradation processes when compared to mRNA which is extremely important once, in a crime scene, biological evidences might be exposed to several unfavorable environmental factors. Recently, published studies were able to identify some specific miRNAs, however their results were not always reproducible by others which can possibly be the reflection of different workflow strategies for their profiling studies. Given the current blast of interest in miRNAs, it is important to acknowledge potential limitations of miRNA profiling, yet, the lack of such studies are evident. This review pretends to gather all the information to date and assessed a multitude of factors that have a potential aptitude to discrediting miRNA profiling, such as: methodological approaches, environmental factors, physiological conditions, gender, pathologies and samples storage. It can be asserted that much has yet to be made, but we pretend to highlight a potential answer for the ultimate question: Can miRNA profiling be used as the forensic biomarker for body fluids identification?

  8. Reactive Agility Performance in Handball; Development and Evaluation of a Sport-Specific Measurement Protocol.

    PubMed

    Spasic, Miodrag; Krolo, Ante; Zenic, Natasa; Delextrat, Anne; Sekulic, Damir

    2015-09-01

    There is no current study that examined sport-specific tests of reactive-agility and change-of-direction-speed (CODS) to replicate real-sport environment in handball (team-handball). This investigation evaluated the reliability and validity of two novel tests designed to assess reactive-agility and CODS of handball players. Participants were female (25.14 ± 3.71 years of age; 1.77 ± 0.09 m and 74.1 ± 6.1 kg) and male handball players (26.9 ± 4.1 years of age; 1.90 ± 0.09 m and 93.90±4.6 kg). Variables included body height, body mass, body mass index, broad jump, 5-m sprint, CODS and reactive-agility tests. Results showed satisfactory reliability for reactive-agility-test and CODS-test (ICC of 0.85-0.93, and CV of 2.4-4.8%). The reactive-agility and CODS shared less than 20% of the common variance. The calculated index of perceptual and reactive capacity (P&RC; ratio between reactive-agility- and CODS-performance) is found to be valid measure in defining true-game reactive-agility performance in handball in both genders. Therefore, the handball athletes' P&RC should be used in the evaluation of real-game reactive-agility performance. Future studies should explore other sport-specific reactive-agility tests and factors associated to such performance in sports involving agile maneuvers. Key pointsReactive agility and change-of-direction-speed should be observed as independent qualities, even when tested over the same course and similar movement templateThe reactive-agility-performance of the handball athletes involved in defensive duties is closer to their non-reactive-agility-score than in their peers who are not involved in defensive dutiesThe handball specific "true-game" reactive-agility-performance should be evaluated as the ratio between reactive-agility and corresponding CODS performance.

  9. Analysis of miRNA profiles identified miR-196a as a crucial mediator of aberrant PI3K/AKT signaling in lung cancer cells.

    PubMed

    Guerriero, Ilaria; D'Angelo, Daniela; Pallante, Pierlorenzo; Santos, Mafalda; Scrima, Marianna; Malanga, Donatella; De Marco, Carmela; Ravo, Maria; Weisz, Alessandro; Laudanna, Carmelo; Ceccarelli, Michele; Falco, Geppino; Rizzuto, Antonia; Viglietto, Giuseppe

    2016-11-17

    Hyperactivation of the PI3K/AKT pathway is observed in most human cancer including lung carcinomas. Here we have investigated the role of miRNAs as downstream targets of activated PI3K/AKT signaling in Non Small Cell Lung Cancer (NSCLC). To this aim, miRNA profiling was performed in human lung epithelial cells (BEAS-2B) expressing active AKT1 (BEAS-AKT1-E17K), active PI3KCA (BEAS-PIK3CA-E545K) or with silenced PTEN (BEAS-shPTEN).Twenty-four differentially expressed miRNAs common to BEAS-AKT1-E17K, BEAS-PIK3CA-E545K and BEAS-shPTEN cells were identified through this analysis, with miR-196a being the most consistently up-regulated miRNA. Interestingly, miR-196a was significantly overexpressed also in human NSCLC-derived cell lines (n=11) and primary lung cancer samples (n=28).By manipulating the expression of miR-196a in BEAS-2B and NCI-H460 cells, we obtained compelling evidence that this miRNA acts downstream the PI3K/AKT pathway, mediating some of the proliferative, pro-migratory and tumorigenic activity that this pathway exerts in lung epithelial cells, possibly through the regulation of FoxO1, CDKN1B (hereafter p27) and HOXA9.

  10. SU-E-T-610: Comparison of Treatment Times Between the MLCi and Agility Multileaf Collimators

    SciTech Connect

    Ramsey, C; Bowling, J

    2014-06-01

    Purpose: The Agility is a new 160-leaf MLC developed by Elekta for use in their Infinity and Versa HD linacs. As compared to the MLCi, the Agility increased the maximum leaf speed from 2 cm/s to 3.5 cm/s, and the maximum primary collimator speed from 1.5 cm/s to 9.0 cm/s. The purpose of this study was to determine if the Agility MLC resulted in improved plan quality and/or shorter treatment times. Methods: An Elekta Infinity that was originally equipped with a 80 leaf MLCi was upgraded to an 160 leaf Agility. Treatment plan quality was evaluated using the Pinnacle planning system with SmartArc. Optimization was performed once for the MLCi and once for the Agility beam models using the same optimization parameters and the same number of iterations. Patient treatment times were measured for all IMRT, VMAT, and SBRT patients treated on the Infinity with the MLCi and Agility MLCs. Treatment times were extracted from the EMR and measured from when the patient first walked into the treatment room until exiting the treatment room. Results: 11,380 delivery times were measured for patients treated with the MLCi, and 1,827 measurements have been made for the Agility MLC. The average treatment times were 19.1 minutes for the MLCi and 20.8 minutes for the Agility. Using a t-test analysis, there was no difference between the two groups (t = 0.22). The dose differences between patients planned with the MLCi and the Agility MLC were minimal. For example, the dose difference for the PTV, GTV, and cord for a head and neck patient planned using Pinnacle were effectively equivalent. However, the dose to the parotid glands was slightly worse with the Agility MLC. Conclusion: There was no statistical difference in treatment time, or any significant dosimetric difference between the Agility MLC and the MLCi.

  11. Genome-wide mRNA and miRNA analysis of peripheral blood mononuclear cells (PBMC) reveals different miRNAs regulating HIV/HCV co-infection.

    PubMed

    Gupta, P; Liu, B; Wu, J Q; Soriano, V; Vispo, E; Carroll, A P; Goldie, B J; Cairns, M J; Saksena, N K

    2014-02-01

    Co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common due to shared transmission routes. The genomic basis of HIV/HCV co-infection and its regulation by microRNA (miRNA) is unknown. Therefore, our objective was to investigate genome-wide mRNA expression and its regulation by miRNA in primary PBMCs derived from 27 patients (5 HCV - mono-infected, 5 HIV-mono-infected, 12 HCV/HIV co-infected, and 5 healthy controls). This revealed 27 miRNAs and 476 mRNAs as differentially expressed (DE) in HCV/HIV co-infection when compared to controls (adj p<0.05). Our study shows the first evidence of miRNAs specific for co-infection, several of which are correlated with key gene targets demonstrating functional relationships to pathways in cancer, immune-function, and metabolism. Notable was the up regulation of HCV-specific miR-122 in co-infection (FC>50, p=4.02E-06), which may have clinical/biological implications.

  12. The miRNA biogenesis in marine bivalves

    PubMed Central

    Rosani, Umberto; Pallavicini, Alberto

    2016-01-01

    Small non-coding RNAs include powerful regulators of gene expression, transposon mobility and virus activity. Among the various categories, mature microRNAs (miRNAs) guide the translational repression and decay of several targeted mRNAs. The biogenesis of miRNAs depends on few gene products, essentially conserved from basal to higher metazoans, whose protein domains allow specific interactions with dsRNA. Here, we report the identification of key genes responsible of the miRNA biogenesis in 32 bivalves, with particular attention to the aquaculture species Mytilus galloprovincialis and Crassostrea gigas. In detail, we have identified and phylogenetically compared eight evolutionary conserved proteins: DROSHA, DGCR8, EXP5, RAN, DICER TARBP2, AGO and PIWI. In mussels, we recognized several other proteins participating in the miRNA biogenesis or in the subsequent RNA silencing. According to digital expression analysis, these genes display low and not inducible expression levels in adult mussels and oysters whereas they are considerably expressed during development. As miRNAs play an important role also in the antiviral responses, knowledge on their production and regulative effects can shed light on essential molecular processes and provide new hints for disease prevention in bivalves. PMID:26989613

  13. miRNA analysis in pancreatic cancer: the Dartmouth experience.

    PubMed

    Abreu, Francine B de; Liu, Xiaoying; Tsongalis, Gregory J

    2017-05-01

    Pancreatic cancer is considered one of the most lethal cancers being the fourth leading cause of cancer deaths in adults in the United States because of the lack of early signs and symptoms and the lack of early detection. Pancreatic ductal adenocarcinoma (PDAC) is the most common histological type among pancreatic cancers, representing 80%-90% of all solid tumors of the pancreas. The majority of PDAC develops from three precursor lesions: pancreatic intraepithelial neoplasia, intraductual papillary mucinous neoplasm and mucinous cystic neoplasm. Although histologic tissue evaluation remains the gold standard for diagnosis, endoscopic ultrasound-guided fine needle aspiration has become the preferred modality for obtaining pathologic confirmation. At Dartmouth-Hitchcock Medical Center (DHMC),we have developed and validated a microRNA (miRNA) panel for patients with pancreatic diseases that can be used in association with the gold standard method for diagnosis. miRNAs have an important role in biological processes, such as apoptosis, metabolism, cell growth and differentiation. In cancer, miRNAs can be classified as either oncogenic or tumor suppressor according to their function in the carcinogenic process. In this study, we describe the expression of many miRNA in benign and malignant pancreatic tissues as well as their clinical significance. For this reason, miRNAs have been considered potential biomarkers of pancreatic diseases that could potentially contribute to an early diagnosis, predict disease progression, accurately monitor disease, contribute to better treatment strategies and reduce mortality by improving disease management.

  14. Microprocessor activity controls differential miRNA biogenesis In Vivo.

    PubMed

    Conrad, Thomas; Marsico, Annalisa; Gehre, Maja; Orom, Ulf Andersson

    2014-10-23

    In miRNA biogenesis, pri-miRNA transcripts are converted into pre-miRNA hairpins. The in vivo properties of this process remain enigmatic. Here, we determine in vivo transcriptome-wide pri-miRNA processing using next-generation sequencing of chromatin-associated pri-miRNAs. We identify a distinctive Microprocessor signature in the transcriptome profile from which efficiency of the endogenous processing event can be accurately quantified. This analysis reveals differential susceptibility to Microprocessor cleavage as a key regulatory step in miRNA biogenesis. Processing is highly variable among pri-miRNAs and a better predictor of miRNA abundance than primary transcription itself. Processing is also largely stable across three cell lines, suggesting a major contribution of sequence determinants. On the basis of differential processing efficiencies, we define functionality for short sequence features adjacent to the pre-miRNA hairpin. In conclusion, we identify Microprocessor as the main hub for diversified miRNA output and suggest a role for uncoupling miRNA biogenesis from host gene expression.

  15. Use of miRNAs as Biomarkers in Sepsis

    PubMed Central

    Dumache, Raluca; Rogobete, Alexandru Florin; Bedreag, Ovidiu Horea; Sarandan, Mirela; Cradigati, Alina Carmen; Papurica, Marius; Dumbuleu, Corina Maria; Nartita, Radu; Sandesc, Dorel

    2015-01-01

    Sepsis is one of the most common causes of death in critical patients. Severe generalized inflammation, infections, and severe physiological imbalances significantly decrease the survival rate with more than 50%. Moreover, monitoring, evaluation, and therapy management often become extremely difficult for the clinician in this type of patients. Current methods of diagnosing sepsis vary based especially on the determination of biochemical-humoral markers, such as cytokines, components of the complement, and proinflammatory and anti-inflammatory compounds. Recent studies highlight the use of new biomarkers for sepsis, namely, miRNAs. miRNAs belong to a class of small, noncoding RNAs with an approximate content of 19–23 nucleotides. Following biochemical and physiological imbalances, the expression of miRNAs in blood or other body fluids changes significantly. Moreover, its stability, specificity, and selectivity make miRNAs ideal candidates for sepsis biomarkers. In conclusion, we can affirm that stable species of circulating miRNAs represent potential biomarkers for monitoring the evolution of sepsis. PMID:26221578

  16. Architecture and performances of the AGILE Telemetry Preprocessing System (TMPPS)

    NASA Astrophysics Data System (ADS)

    Trifoglio, M.; Bulgarelli, A.; Gianotti, F.; Lazzarotto, F.; Di Cocco, G.; Fuschino, F.; Tavani, M.

    2008-07-01

    AGILE is an Italian Space Agency (ASI) satellite dedicated to high energy Astrophysics. It was launched successfully on 23 April 2007, and it has been operated by the AGILE Ground Segment, consisting of the Ground Station located in Malindi (Kenia), the Mission Operations Centre (MOC) and the AGILE Data Centre (ADC) established in Italy, at Telespazio in Fucino and at the ASI Science Data Centre (ASDC) in Frascati respectively. Due to the low equatorial orbit at ~ 530 Km. with inclination angle of ~ 2.5°, the satellite passes over the Ground Station every ~ 100'. During the visibility period of . ~ 12', the Telemetry (TM) is down linked through two separated virtual channels, VC0 and VC1. The former is devoted to the real time TM generated during the pass at the average rate of 50 Kbit/s and is directly relayed to the Control Centre. The latter is used to downlink TM data collected on the satellite on-board mass memory during the non visibility period. This generates at the Ground Station a raw TM file of up to 37 MByte. Within 20' after the end of the contact, both the real time and mass memory TM arrive at ADC through the dedicated VPN ASINet. Here they are automatically detected and ingested by the TMPPS pipeline in less than 5 minutes. The TMPPS archives each TM file and sorts its packets into one stream for each of the different TM layout. Each stream is processed in parallel in order to unpack the various telemetry field and archive them into suitable FITS files. Each operation is tracked into a MySQL data base which interfaces the TMPPS pipeline to the rest of the scientific pipeline running at ADC. In this paper the architecture and the performance of the TMPPS will be described and discussed.

  17. Wired Widgets: Agile Visualization for Space Situational Awareness

    NASA Astrophysics Data System (ADS)

    Gerschefske, K.; Witmer, J.

    2012-09-01

    Continued advancement in sensors and analysis techniques have resulted in a wealth of Space Situational Awareness (SSA) data, made available via tools and Service Oriented Architectures (SOA) such as those in the Joint Space Operations Center Mission Systems (JMS) environment. Current visualization software cannot quickly adapt to rapidly changing missions and data, preventing operators and analysts from performing their jobs effectively. The value of this wealth of SSA data is not fully realized, as the operators' existing software is not built with the flexibility to consume new or changing sources of data or to rapidly customize their visualization as the mission evolves. While tools like the JMS user-defined operational picture (UDOP) have begun to fill this gap, this paper presents a further evolution, leveraging Web 2.0 technologies for maximum agility. We demonstrate a flexible Web widget framework with inter-widget data sharing, publish-subscribe eventing, and an API providing the basis for consumption of new data sources and adaptable visualization. Wired Widgets offers cross-portal widgets along with a widget communication framework and development toolkit for rapid new widget development, giving operators the ability to answer relevant questions as the mission evolves. Wired Widgets has been applied in a number of dynamic mission domains including disaster response, combat operations, and noncombatant evacuation scenarios. The variety of applications demonstrate that Wired Widgets provides a flexible, data driven solution for visualization in changing environments. In this paper, we show how, deployed in the Ozone Widget Framework portal environment, Wired Widgets can provide an agile, web-based visualization to support the SSA mission. Furthermore, we discuss how the tenets of agile visualization can generally be applied to the SSA problem space to provide operators flexibility, potentially informing future acquisition and system development.

  18. Therapeutics targeting angiogenesis: genetics and epigenetics, extracellular miRNAs and signaling networks (Review).

    PubMed

    Katoh, Masaru

    2013-10-01

    Angiogenesis is a process of neovascular formation from pre-existing blood vessels, which consists of sequential steps for vascular destabilization, angiogenic sprouting, lumen formation and vascular stabilization. Vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), angiopoietin, Notch, transforming growth factor-β (TGF-β), Hedgehog and WNT signaling cascades orchestrate angiogenesis through the direct or indirect regulation of quiescence, migration and the proliferation of endothelial cells. Small-molecule compounds and human/humanized monoclonal antibodies interrupting VEGF signaling have been developed as anti-angiogenic therapeutics for cancer and neovascular age-related macular degeneration (AMD). Gene or protein therapy delivering VEGF, FGF2 or FGF4, as well as cell therapy using endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs) or induced pluripotent stem cells (iPSCs) have been developed as pro-angiogenic therapeutics for ischemic heart disease and peripheral vascular disease. Anti-angiogenic therapy for cancer and neovascular AMD is more successful than pro-angiogenic therapy for cardiovascular diseases, as VEGF-signal interruption is technically feasible compared with vascular re-construction. Common and rare genetic variants are detected using array-based technology and personal genome sequencing, respectively. Drug and dosage should be determined based on personal genotypes of VEGF and other genes involved in angiogenesis. As epigenetic alterations give rise to human diseases, polymer-based hydrogel film may be utilized for the delivery of drugs targeting epigenetic processes and angiogenesis as treatment modalities for cardiovascular diseases. Circulating microRNAs (miRNAs) in exosomes and microvesicles are applied as functional biomarkers for diagnostics and prognostics, while synthetic miRNAs in polymer-based nanoparticles are applicable for therapeutics. A more profound understanding of the spatio

  19. An Agile Enterprise Regulation Architecture for Health Information Security Management

    PubMed Central

    Chen, Ying-Pei; Hsieh, Sung-Huai; Chien, Tsan-Nan; Chen, Heng-Shuen; Luh, Jer-Junn; Lai, Jin-Shin; Lai, Feipei; Chen, Sao-Jie

    2010-01-01

    Abstract Information security management for healthcare enterprises is complex as well as mission critical. Information technology requests from clinical users are of such urgency that the information office should do its best to achieve as many user requests as possible at a high service level using swift security policies. This research proposes the Agile Enterprise Regulation Architecture (AERA) of information security management for healthcare enterprises to implement as part of the electronic health record process. Survey outcomes and evidential experiences from a sample of medical center users proved that AERA encourages the information officials and enterprise administrators to overcome the challenges faced within an electronically equipped hospital. PMID:20815748

  20. An agile enterprise regulation architecture for health information security management.

    PubMed

    Chen, Ying-Pei; Hsieh, Sung-Huai; Cheng, Po-Hsun; Chien, Tsan-Nan; Chen, Heng-Shuen; Luh, Jer-Junn; Lai, Jin-Shin; Lai, Feipei; Chen, Sao-Jie

    2010-09-01

    Information security management for healthcare enterprises is complex as well as mission critical. Information technology requests from clinical users are of such urgency that the information office should do its best to achieve as many user requests as possible at a high service level using swift security policies. This research proposes the Agile Enterprise Regulation Architecture (AERA) of information security management for healthcare enterprises to implement as part of the electronic health record process. Survey outcomes and evidential experiences from a sample of medical center users proved that AERA encourages the information officials and enterprise administrators to overcome the challenges faced within an electronically equipped hospital.

  1. Perspectives on Industrial Innovation from Agilent, HP, and Bell Labs

    NASA Astrophysics Data System (ADS)

    Hollenhorst, James

    2014-03-01

    Innovation is the life blood of technology companies. I will give perspectives gleaned from a career in research and development at Bell Labs, HP Labs, and Agilent Labs, from the point of view of an individual contributor and a manager. Physicists bring a unique set of skills to the corporate environment, including a desire to understand the fundamentals, a solid foundation in physical principles, expertise in applied mathematics, and most importantly, an attitude: namely, that hard problems can be solved by breaking them into manageable pieces. In my experience, hiring managers in industry seldom explicitly search for physicists, but they want people with those skills.

  2. Development of EarthCube Governance: An Agile Approach

    NASA Astrophysics Data System (ADS)

    Pearthree, G.; Allison, M. L.; Patten, K.

    2013-12-01

    Governance of geosciences cyberinfrastructure is a complex and essential undertaking, critical in enabling distributed knowledge communities to collaborate and communicate across disciplines, distances, and cultures. Advancing science with respect to 'grand challenges," such as global climate change, weather prediction, and core fundamental science, depends not just on technical cyber systems, but also on social systems for strategic planning, decision-making, project management, learning, teaching, and building a community of practice. Simply put, a robust, agile technical system depends on an equally robust and agile social system. Cyberinfrastructure development is wrapped in social, organizational and governance challenges, which may significantly impede progress. An agile development process is underway for governance of transformative investments in geosciences cyberinfrastructure through the NSF EarthCube initiative. Agile development is iterative and incremental, and promotes adaptive planning and rapid and flexible response. Such iterative deployment across a variety of EarthCube stakeholders encourages transparency, consensus, accountability, and inclusiveness. A project Secretariat acts as the coordinating body, carrying out duties for planning, organizing, communicating, and reporting. A broad coalition of stakeholder groups comprises an Assembly (Mainstream Scientists, Cyberinfrastructure Institutions, Information Technology/Computer Sciences, NSF EarthCube Investigators, Science Communities, EarthCube End-User Workshop Organizers, Professional Societies) to serve as a preliminary venue for identifying, evaluating, and testing potential governance models. To offer opportunity for broader end-user input, a crowd-source approach will engage stakeholders not involved otherwise. An Advisory Committee from the Earth, ocean, atmosphere, social, computer and library sciences is guiding the process from a high-level policy point of view. Developmental

  3. Planning and scheduling for agile manufacturers: The Pantex Process Model

    SciTech Connect

    Kjeldgaard, E.A.; Jones, D.A.; List, G.F.; Tumquist, M.A.

    1998-02-01

    Effective use of resources that are shared among multiple products or processes is critical for agile manufacturing. This paper describes the development and implementation of a computerized model to support production planning in a complex manufacturing system at the Pantex Plant, a US Department of Energy facility. The model integrates two different production processes (nuclear weapon disposal and stockpile evaluation) that use common facilities and personnel at the plant. The two production processes are characteristic of flow-shop and job shop operations. The model reflects the interactions of scheduling constraints, material flow constraints, and the availability of required technicians and facilities. Operational results show significant productivity increases from use of the model.

  4. Production planning tools and techniques for agile manufacturing

    SciTech Connect

    Kjeldgaard, E.A.; Jones, D.A.; List, G.F.; Turnquist, M.A.

    1996-10-01

    Effective use of resources shared among multiple products or processes is critical for agile manufacturing. This paper describes development and implementation of a computerized model to support production planning in a complex manufacturing system at Pantex Plant. The model integrates two different production processes (nuclear weapon dismantlement and stockpile evaluation) which use common facilities and personnel, and reflects the interactions of scheduling constraints, material flow constraints, and resource availability. These two processes reflect characteristics of flow-shop and job-shop operations in a single facility. Operational results from using the model are also discussed.

  5. Impact of emerging technologies on future combat aircraft agility

    NASA Technical Reports Server (NTRS)

    Nguyen, Luat T.; Gilert, William P.

    1990-01-01

    The foreseeable character of future within-visual-range air combat entails a degree of agility which calls for the integration of high-alpha aerodynamics, thrust vectoring, intimate pilot/vehicle interfaces, and advanced weapons/avionics suites, in prospective configurations. The primary technology-development programs currently contributing to these goals are presently discussed; they encompass the F-15 Short Takeoff and Landing/Maneuver Technology Demonstrator Program, the Enhanced Fighter Maneuverability Program, the High Angle-of-Attack Technology Program, and the X-29 Technology Demonstrator Program.

  6. Waveform-Agile Tracking In Heavy Sea Clutter

    DTIC Science & Technology

    2007-01-01

    Waveform-Agile Tracking In Heavy Sea Clutter Sandeep P. Sira , Antonia Papandreou-Suppappola, Darryl Morrell†, and Douglas Cochran SenSIP Center...to a non-adaptive system. The paper is organized as follows. In Section II, we describe the models for the target dynamics, clutter, and observations ...dependence on zs[n]. C. Observations Model At the end of Sub-dwell 2 of the kth dwell, the measurement provided to the tracker is Yk = [yTn̂0−nv

  7. Diagnostic, Prognostic, and Therapeutic Value of Circulating miRNAs in Heart Failure Patients Associated with Oxidative Stress

    PubMed Central

    Ali Sheikh, Md Sayed; Salma, Umme; Zhang, Baohai; Chen, Jimei; Zhuang, Jian; Ping, Zhu

    2016-01-01

    Heart failure is a major public health problem especially in the aging population (≥65 years old), affecting nearly 5 million Americans and 15 million European people. Effective management of heart failure (HF) depends on a correct and rapid diagnosis. Presently, BNP (brain natriuretic peptide) or N-terminal pro-brain natriuretic peptide (NT-proBNP) assay is generally accepted by the international community for diagnostic evaluation and risk stratification of patients with HF. However, regardless of its widespread clinical use, BNP is still encumbered by reduced specificity. As a result, diagnosis of heart failure remains challenging. Although significant improvement happened in the clinical management of HF over the last 2 decades, traditional treatments are ultimately ineffective in many patients who progress to advanced HF. Therefore, a novel diagnostic, prognostic biomarker and new therapeutic approach are required for clinical management of HF patients. Circulating miRNAs seem to be the right choice for novel noninvasive biomarkers as well as new treatment strategies for HF. In this review, we briefly discuss the diagnostic, prognostic, and therapeutic role of circulating miRNAs in heart failure patients. We also mentioned our own technique of extraction of RNA and detection of circulating miRNAs from human plasma and oxidative stress associated miRNAs with HF. PMID:27379177

  8. Epstein-Barr viral miRNAs inhibit antiviral CD4+ T cell responses targeting IL-12 and peptide processing

    PubMed Central

    Moosmann, Andreas; Mautner, Josef; Zielinski, Christina

    2016-01-01

    Epstein-Barr virus (EBV) is a tumor virus that establishes lifelong infection in most of humanity, despite eliciting strong and stable virus-specific immune responses. EBV encodes at least 44 miRNAs, most of them with unknown function. Here, we show that multiple EBV miRNAs modulate immune recognition of recently infected primary B cells, EBV's natural target cells. EBV miRNAs collectively and specifically suppress release of proinflammatory cytokines such as IL-12, repress differentiation of naive CD4+ T cells to Th1 cells, interfere with peptide processing and presentation on HLA class II, and thus reduce activation of cytotoxic EBV-specific CD4+ effector T cells and killing of infected B cells. Our findings identify a previously unknown viral strategy of immune evasion. By rapidly expressing multiple miRNAs, which are themselves nonimmunogenic, EBV counteracts recognition by CD4+ T cells and establishes a program of reduced immunogenicity in recently infected B cells, allowing the virus to express viral proteins required for establishment of life-long infection. PMID:27621419

  9. Ultrasensitive electrochemical detection of miRNA-21 by using an iridium(III) complex as catalyst.

    PubMed

    Miao, Xiangmin; Wang, Wanhe; Kang, Tianshu; Liu, Jinbiao; Shiu, Kwok-Keung; Leung, Chung-Hang; Ma, Dik-Lung

    2016-12-15

    The ultrasensitive electrochemical detection of miRNA-21 was realized by using a novel redox and catalytic "all-in-one" mechanism with an iridium(III) complex as a catalyst. To construct such a sensor, a capture probe (CP) was firstly immobilized onto the gold electrode surface. In the presence of miRNA-21, a sandwiched DNA complex could form between CP and a methylene blue (MB) labeled G-rich detection probe modified onto a gold nanoparticle (AuNP) surface (DP-AuNPs). Upon addition of K(+), the structure of DP changed to a G-quadruplex. Then, the iridium(III) complex could selectively interact with the G-quadruplex, catalyzing the reduction of H2O2, which was accompanied by an electrochemical signal change using MB as an electron mediator. Under optimal conditions, the electrochemical signal of MB reduction peak was proportional to miRNA concentration in the range from 5.0 fM to 1.0 pM, with a detection limit of 1.6 fM. In addition, satisfactory results were obtained for miRNA-21 detection in human serum samples, indicating a potential application of the sensor for bioanalysis.

  10. Computer vision challenges and technologies for agile manufacturing

    NASA Astrophysics Data System (ADS)

    Molley, Perry A.

    1996-02-01

    Sandia National Laboratories, a Department of Energy laboratory, is responsible for maintaining the safety, security, reliability, and availability of the nuclear weapons stockpile for the United States. Because of the changing national and global political climates and inevitable budget cuts, Sandia is changing the methods and processes it has traditionally used in the product realization cycle for weapon components. Because of the increasing age of the nuclear stockpile, it is certain that the reliability of these weapons will degrade with time unless eventual action is taken to repair, requalify, or renew them. Furthermore, due to the downsizing of the DOE weapons production sites and loss of technical personnel, the new product realization process is being focused on developing and deploying advanced automation technologies in order to maintain the capability for producing new components. The goal of Sandia's technology development program is to create a product realization environment that is cost effective, has improved quality and reduced cycle time for small lot sizes. The new environment will rely less on the expertise of humans and more on intelligent systems and automation to perform the production processes. The systems will be robust in order to provide maximum flexibility and responsiveness for rapidly changing component or product mixes. An integrated enterprise will allow ready access to and use of information for effective and efficient product and process design. Concurrent engineering methods will allow a speedup of the product realization cycle, reduce costs, and dramatically lessen the dependency on creating and testing physical prototypes. Virtual manufacturing will allow production processes to be designed, integrated, and programed off-line before a piece of hardware ever moves. The overriding goal is to be able to build a large variety of new weapons parts on short notice. Many of these technologies that are being developed are also

  11. Robotics of human movements.

    PubMed

    van der Smagt, Patrick; Grebenstein, Markus; Urbanek, Holger; Fligge, Nadine; Strohmayr, Michael; Stillfried, Georg; Parrish, Jonathon; Gustus, Agneta

    2009-01-01

    The construction of robotic systems that can move the way humans do, with respect to agility, stability and precision, is a necessary prerequisite for the successful integration of robotic systems in human environments. We explain human-centered views on robotics, based on the three basic ingredients (1) actuation; (2) sensing; and (3) control, and formulate detailed examples thereof.

  12. What makes a blood cell based miRNA expression pattern disease specific? - A miRNome analysis of blood cell subsets in lung cancer patients and healthy controls

    PubMed Central

    Dahmke, Indra N.; Galata, Valentina; Huwer, Hanno; Stehle, Ingo; Bals, Robert; Keller, Andreas; Meese, Eckart

    2014-01-01

    There is evidence of blood-borne miRNA signatures for various human diseases. To dissect the origin of disease-specific miRNA expression in human blood, we separately analyzed the miRNome of different immune cell subtypes, each in lung cancer patients and healthy individuals. Each immune cell type revealed a specific miRNA expression pattern also dependinging on the cell origin, line of defense, and function. The overall expression pattern of each leukocyte subtype showed great similarities between patients and controls. However, for each cell subtype we identified miRNAs that were deregulated in lung cancer patients including hsa-miR-21, a well-known oncomiR associated with poor lung cancer prognosis that was up-regulated in all leukocyte subtype comparisons of cancer versus controls. While the miRNome of cells of the adaptive immune system allowed only a weak separation between patients and controls, cells of the innate immune system allowed perfect or nearly perfect classification. Leukocytes of lung cancer patients show a cancer-specific miRNA expression profile. Our data also show that cancer specific miRNA expression pattern of whole blood samples are not determined by a single cell type. The data indicate that additional blood components, like erythrocytes, platelets, or exosomes might contribute to the disease specificity of a miRNA signature. PMID:25344866

  13. Regulation of the microRNA 200b (miRNA-200b) by transcriptional regulators PEA3 and ELK-1 protein affects expression of Pin1 protein to control anoikis.

    PubMed

    Zhang, Xusen; Zhang, Bailin; Gao, Jidong; Wang, Xiang; Liu, Zhihua

    2013-11-08

    MicroRNA (miRNA) 200s regulate E-cadherin by directly targeting ZEB1/ZEB2, which are transcriptional repressors of E-cadherin. Decreased expression of E-cadherin results in cancer cells losing interaction with the extracellular matrix and detaching from the primary tumor. Normally, cells will undergo anoikis after losing interaction with the extracellular matrix. Cancer cells must, therefore, possess the ability to resist anoikis during the process of metastasis. Here we show that miRNA-200b regulates anoikis by directly targeting the 3' UTR of Pin1 mRNA and regulating Pin1 expression at the translational level. We found that down-regulation of miRNA-200b promotes cancer cells survival during metastasis, and the homeless state of these cells resulted in decreased expression of miRNA-200b in the MCF-7 cell line. We also found that expression of miRNA-200b is down-regulated in human breast cancer during lymph node metastasis, which has a significant negative correlation with Pin1 expression. Two members of the ETS (E-26) family (PEA3 and ELK-1) regulate the expression of miRNA-200b. PEA3 promotes the expression of miRNA-200b, and ELK-1 is a transcriptional repressor of miRNA-200b. In addition, miRNA-200b regulates the activity of PEA3 and ELK-1 via the Pin1-pERK pathway and forms self-regulated feedback loops. This study characterizes the role of miRNA-200b in the regulation of anoikis and demonstrates the regulation of its own expression in the process of metastasis.

  14. Serum profiling identifies novel muscle miRNA and cardiomyopathy-related miRNA biomarkers in Golden Retriever muscular dystrophy dogs and Duchenne muscular dystrophy patients.

    PubMed

    Jeanson-Leh, Laurence; Lameth, Julie; Krimi, Soraya; Buisset, Julien; Amor, Fatima; Le Guiner, Caroline; Barthélémy, Inès; Servais, Laurent; Blot, Stéphane; Voit, Thomas; Israeli, David

    2014-11-01

    Duchenne muscular dystrophy (DMD) is a fatal, X-linked neuromuscular disease that affects 1 boy in 3500 to 5000 boys. The golden retriever muscular dystrophy dog is the best clinically relevant DMD animal model. Here, we used a high-thoughput miRNA sequencing screening for identification of candidate serum miRNA biomarkers in golden retriever muscular dystrophy dogs. We confirmed the dysregulation of the previously described muscle miRNAs, miR-1, miR-133, miR-206, and miR-378, and identified a new candidate muscle miRNA, miR-95. We identified two other classes of dysregulated serum miRNAs in muscular dystrophy: miRNAs belonging to the largest known miRNA cluster that resides in the imprinting DLK1-DIO3 genomic region and miRNAs associated with cardiac disease, including miR-208a, miR-208b, and miR-499. No simple correlation was identified between serum levels of cardiac miRNAs and cardiac functional parameters in golden retriever muscular dystrophy dogs. Finally, we confirmed a dysregulation of miR-95, miR-208a, miR-208b, miR-499, and miR-539 in a small cohort of DMD patients. Given the interspecies conservation of miRNAs and preliminary data in DMD patients, these newly identified dysregulated miRNAs are strong candidate biomarkers for DMD patients.

  15. Relationship Between Reactive Agility and Change of Direction Speed in Amateur Soccer Players.

    PubMed

    Matlák, János; Tihanyi, József; Rácz, Levente

    2016-06-01

    The aim of the study was to assess the relationship between reactive agility and change of direction speed (CODS) among amateur soccer players using running tests with four directional changes. Sixteen amateur soccer players (24.1 ± 3.3 years; 72.4 ± 7.3 kg; 178.7 ± 6 cm) completed CODS and reactive agility tests with four changes of direction using the SpeedCourt™ system (Globalspeed GmbH, Hemsbach, Germany). Countermovement jump (CMJ) height and maximal foot tapping count (completed in 3 seconds) were also measured with the same device. In the reactive agility test, participants had to react to a series of light stimuli projected onto a screen. Total time was shorter in the CODS test than in the reactive agility test (p < 0.001). Nonsignificant correlations were found among variables measured in the CODS, reactive agility, and CMJ tests. Low common variance (r = 0.03-0.18) was found between CODS and reactive agility test variables. The results of this study underscore the importance of cognitive factors in reactive agility performance and suggest that specific methods may be required for training and testing reactive agility and CODS.

  16. The Preparation of Cognitively Agile Principals for Turnaround Schools: A Leadership Preparation Programme Study

    ERIC Educational Resources Information Center

    Reyes-Guerra, Daniel; Pisapia, John; Mick, Annie

    2016-01-01

    The purpose of this study was to examine the ability of two educational leadership university programmes to improve the cognitive agility of their graduates. The research looked to discover whether the aspiring principals exited the programmes with an increased ability to employ cognitive agility--the ability to use the multiple thinking skills of…

  17. The Impacts of Agile Development Methodology Use on Project Success: A Contingency View

    ERIC Educational Resources Information Center

    Tripp, John F.

    2012-01-01

    Agile Information Systems Development Methods have emerged in the past decade as an alternative manner of managing the work and delivery of information systems development teams, with a large number of organizations reporting the adoption & use of agile methods. The practitioners of these methods make broad claims as to the benefits of their…

  18. Impact of Business Intelligence and IT Infrastructure Flexibility on Competitive Advantage: An Organizational Agility Perspective

    ERIC Educational Resources Information Center

    Chen, Xiaofeng

    2012-01-01

    There is growing use of business intelligence (BI) for better management decisions in industry. However, empirical studies on BI are still scarce in academic research. This research investigates BI from an organizational agility perspective. Organizational agility is the ability to sense and respond to market opportunities and threats with speed,…

  19. Project-Method Fit: Exploring Factors That Influence Agile Method Use

    ERIC Educational Resources Information Center

    Young, Diana K.

    2013-01-01

    While the productivity and quality implications of agile software development methods (SDMs) have been demonstrated, research concerning the project contexts where their use is most appropriate has yielded less definitive results. Most experts agree that agile SDMs are not suited for all project contexts. Several project and team factors have been…

  20. The NERV Methodology: Non-Functional Requirements Elicitation, Reasoning and Validation in Agile Processes

    ERIC Educational Resources Information Center

    Domah, Darshan

    2013-01-01

    Agile software development has become very popular around the world in recent years, with methods such as Scrum and Extreme Programming (XP). Literature suggests that functionality is the primary focus in Agile processes while non-functional requirements (NFR) are either ignored or ill-defined. However, for software to be of good quality both…

  1. Utilization of an agility assessment module in analysis and optimization of preliminary fighter configuration

    NASA Technical Reports Server (NTRS)

    Ngan, Angelen; Biezad, Daniel

    1996-01-01

    A study has been conducted to develop and to analyze a FORTRAN computer code for performing agility analysis on fighter aircraft configurations. This program is one of the modules of the NASA Ames ACSYNT (AirCraft SYNThesis) design code. The background of the agility research in the aircraft industry and a survey of a few agility metrics are discussed. The methodology, techniques, and models developed for the code are presented. The validity of the existing code was evaluated by comparing with existing flight test data. A FORTRAN program was developed for a specific metric, PM (Pointing Margin), as part of the agility module. Example trade studies using the agility module along with ACSYNT were conducted using a McDonnell Douglas F/A-18 Hornet aircraft model. Tile sensitivity of thrust loading, wing loading, and thrust vectoring on agility criteria were investigated. The module can compare the agility potential between different configurations and has capability to optimize agility performance in the preliminary design process. This research provides a new and useful design tool for analyzing fighter performance during air combat engagements in the preliminary design.

  2. 76 FR 59456 - ASGI Agility Income Fund, et al.; Notice of Application

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-26

    ... sales loads (``CDSCs''). Applicants: ASGI Agility Income Fund (``Agility Fund''), ASGI Aurora Opportunities Fund, LLC (``Aurora Fund''), and ASGI Corbin Multi- Strategy Fund, LLC (``Corbin Fund'') (each a... Aurora Fund and the Corbin Fund are each organized as a Delaware limited liability company. The...

  3. Reliability of a Field Test of Defending and Attacking Agility in Australian Football and Relationships to Reactive Strength.

    PubMed

    Young, Warren B; Murray, Mitch P

    2017-02-01

    Young, WB and Murray, MP. Reliability of a field test of defending and attacking agility in Australian football and relationships to reactive strength. J Strength Cond Res 31(2): 509-516, 2017-Defending and attacking agility tests for Australian football do not exist, and it is unknown whether any physical qualities correlate with these types of agility. The purposes of this study were to develop new field tests of defending and attacking agility for Australian Rules football, to determine whether they were reliable, and to describe the relationship between the agility